Health Effects Support Document for Aldrin/ Dieldrin Printed on Recycled Paper Health Effects Support Document for Aldrin/ Dieldrin Prepared for:

U. S. Environmental Protection Agency Office of Water ( 4304T) Health and Ecological Criteria Division Washington, DC 20460 www. epa. gov/ safewater/ ccl/ pdf/ aldrindieldrin. pdf EPA 822 R 03 001 February 2003 iii Aldrin/ Dieldrin   February 2003 FOREWORD The Safe Drinking Water Act ( SDWA), as amended in 1996, requires the Administrator of the Environmental Protection Agency to establish a list of contaminants to aid the agency in regulatory priority setting for the drinking water program. In addition, SDWA requires EPA to make regulatory determinations for no fewer than five contaminants by August 2001. The criteria used to determine whether or not to regulate a chemical on the CCL are as follows:

The contaminant may have an adverse effect on the health of persons.

The contaminant is known to occur or there is a substantial likelihood that the contaminant will occur in public water systems with a frequency and at levels of public health concern.

In the sole judgment of the administrator, regulation of such contaminant presents a meaningful opportunity for health risk reduction for persons served by public water systems.

The Agency's findings for all three statutory criteria are used in order to make a determination to regulate a contaminant. The Agency may determine that there is no need for a regulation when a contaminant fails to meet one of the statutory criteria. A decision not to regulate is considered a final agency action and is subject to judicial review.

This document provides the health effects basis for the preliminary regulatory determination for aldrin and dieldrin. In arriving at the preliminary regulatory determination for these two contaminants, data on toxicokinetics, human exposure, acute and chronic toxicity to animals and humans, epidemiology, and mechanisms of toxicity were evaluated. In order to avoid wasteful duplication of effort, information from the following risk assessments by the EPA and other government agencies were used in development of this document.

ATSDR. 2000. Agency for Toxic Substances and Disease Registry. Draft Toxicological Profile for Aldrin/ Dieldrin: Update. Atlanta, GA: U. S. Department of Health and Human Services.

ATSDR. 1993. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Aldrin/ Dieldrin. Atlanta, GA: USDepartment of Health and Human Services.

USEPA. 1992. US Environmental Protection Agency. Aldrin Drinking Water Health Advisory. Office of Water.

USEPA. 1988. US Environmental Protection Agency. Dieldrin Drinking Water Health Advisory. Office of Water. iv Aldrin/ Dieldrin   February 2003 USEPA. 1987a. US Environmental Protection Agency. Integrated Risk Information System ( IRIS): Dieldrin. Cincinnati, OH.

USEPA. 1987b. US Environmental Protection Agency. Carcinogenicity assessment of Dieldrin and Aldrin. ( CAG).

USEPA. 1986. US Environmental Protection Agency. Integrated Risk Information System ( IRIS): Aldrin. Cincinnati, OH.

IARC. 1987. International Agency for Research on Cancer. Evaluation of the carcinogenic risk of chemicals to humans. Overall evaluations of carcinogenicity. Suppl. 7: 88 89.

IARC. 1982. International Agency for Research on Cancer. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Chemicals, industry process and industries associated with cancer in humans. IARC Monographs. Vols. 1 29, Supplement 4. Geneva: World Health Organization.

IARC. 1974a. International Agency for Research on Cancer. Evaluation of the carcinogenic risk of chemicals to humans. Aldrin. Lyon, France: IARC Monograph 5: 25 38.

IARC. 1974b. International Agency for Research on Cancer. Evaluation of the carcinogenic risk of chemicals to humans. Dieldrin. Lyon, France: IARC Monograph 5: 125 156.

In cases where the information in this document originates from one of the references above, a citation to the source document is provided with the bibliographic information in the reference section. Primary references were used for all key studies. Data from the published risk assessments were supplemented with information from literature searches conducted in 2000. Specific emphasis is placed on dose response information and exposure estimates in making the regulatory determination for aldrin and dieldrin. Dose reponse conclusions for noncancer effects are reflected in the Reference Dose ( RfD).

Generally, a RfD is provided as the assessment of long term toxic effects other than carcinogenicity. RfD determination assumes that thresholds exist for certain toxic effects, such as cellular necrosis. It is expressed in terms of milligrams per kilogram per day ( mg/ kg day). In general, the RfD is an estimate ( with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population ( including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.

The carcinogenicity assessment for aldrin and dieldrin includes a formal hazard identification. Hazard identification is a weight of evidence judgement of the likelihood that the agent is a human carcinogen via the oral route and the conditions under which the carcinogenic effects may be expressed. v Aldrin/ Dieldrin   February 2003 Guidelines that were used in the development of this assessment may include the following: the Guidelines for Carcinogen Risk Assessment ( USEPA, 1986a), Guidelines for the Health Risk Assessment of Chemical Mixtures ( USEPA, 1986b), Guidelines for Mutagenicity Risk Assessment ( USEPA, 1986c), Guidelines for Developmental Toxicity Risk Assessment ( USEPA, 1991), Proposed Guidelines for Carcinogen Risk Assessment ( 1996a), Guidelines for Reproductive Toxicity Risk Assessment ( USEPA, 1996b), and Guidelines for Neurotoxicity Risk Assessment ( USEPA, 1998a); Recommendations for and Documentation of Biological Values for Use in Risk Assessment ( USEPA, 1988); and Health Effects Testing Guidelines ( OPPTS series 870, 1996 drafts; USEPA 40 CFR Part 798, 1997; Peer Review and Peer Involvement at the U. S. Environmental Protection Agency ( USEPA, 1994c); Use of the Benchmark Dose Approach in Health Risk Assessment ( USEPA, 1995b); Science Policy Council Handbook: Peer Review ( USEPA, 1998b, 2000a); Memorandum from EPA Administrator, Carol Browner, dated March 21, 1995, Policy for Risk Characterization; Science Policy Council Handbook: Risk Characterization ( USEPA, 2000b).

The section on aldrin and dieldrin occurrence and exposure through potable water in this document was developed by the Office of Ground Water and Drinking Water. It is based primarily on unregulated contaminant monitoring ( UCM) data collected under SDWA. The UCM data are supplemented with ambient water data, as well as information on production, use, and discharge. vi Aldrin/ Dieldrin   February 2003 ACKNOWLEDGMENTS This document was prepared under U. S. EPA Contract No. 68 C 01 002, Work Assignment No. B 11, with Sciences International, Alexandria, VA. The Lead Scientist is Amal M. Mahfouz, Ph. D., Health and Ecological Criteria Division, Office of Science and Technology, Office of Water. vii Aldrin/ Dieldrin   February 2003 TABLE OF CONTENTS FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii ACKNOWLEDGMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi LIST OF TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x LIST OF FIGURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 1.0 EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 2.0 IDENTITY: PHYSICAL AND CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . 2 1 3.0 USES AND ENVIRONMENTAL FATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 3.1 Uses and Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1 3.2 Environmental Release and Fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 4.0 EXPOSURE FROM DRINKING WATER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.1 ALDRIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.1.1 Ambient Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1 4.1.2 Drinking Water Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 4.1.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 13 4.2 DIELDRIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 19 4.2.1 Ambient Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 19 4.2.2 Drinking Water Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 22 4.2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 35 5.0 EXPOSURE FROM ENVIRONMENTAL MEDIA OTHER THAN WATER . . . . . . 5 1 5.1 Exposure from Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 5.1.1 Exposures of the General Population . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1 5.1.2 Exposures of Subpopulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 7 5.2 Exposure from Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 8 5.2.1 Exposures of the General Population . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 8 5.2.2 Exposures of Subpopulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 11 5.3 Exposure from Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 11 5.3.1 Exposures of the General Population . . . . . . . . . . . . . . . . . . . . . . . . . . 5 11 5.3.2 Exposures of Subpopulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 12 5.4 Other Residential Exposures ( Not Drinking Water Related) . . . . . . . . . . . . . . 5 13 5.5 Summary of Exposure to Aldrin/ Dieldrin in Media Other Than Water . . . . . 5 15 6.0 TOXICOKINETICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 6.1 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1 viii Aldrin/ Dieldrin   February 2003 6.2 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2 6.3 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 11 6.4 Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 17 7.0 HAZARD IDENTIFICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 7.1 Human Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 7.1.1 Short Term Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1 7.1.2 Long Term and Epidemiological Studies . . . . . . . . . . . . . . . . . . . . . . . 7 2 7.2 Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 5 7.2.1 Acute Toxicity ( Oral, Inhalation, Dermal) . . . . . . . . . . . . . . . . . . . . . . . 7 5 7.2.2 Short Term Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 6 7.2.3 Subchronic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 7 7.2.4 Neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 9 7.2.5 Developmental/ Reproductive Toxicity . . . . . . . . . . . . . . . . . . . . . . . . 7 12 7.2.6 Chronic Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 16 7.2.7 Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 20 7.3 Other Key Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 25 7.3.1 Mutagenicity/ Genotoxicity Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 25 7.3.2 Immunotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 27 7.3.3 Hormonal Disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 28 7.3.4 Physiological or Mechanistic Studies . . . . . . . . . . . . . . . . . . . . . . . . . 7 28 7.3.5 Structure Activity Relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 32 7.4 Hazard Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 33 7.4.1 Synthesis and Evaluation of Noncancer Effects . . . . . . . . . . . . . . . . . 7 33 7.4.2 Synthesis and Evaluation of Carcinogenic Effects . . . . . . . . . . . . . . . 7 34 7.4.3 Mode of Action and Implications in Cancer Assessment . . . . . . . . . . 7 36 7.4.4 Weight of Evidence Evaluation for Carcinogenicity . . . . . . . . . . . . . . 7 38 7.4.5 Sensitive Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 39 8.0 DOSE RESPONSE ASSESSMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1 Dose Response for Non Cancer Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1.1 Reference Dose Determination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 1 8.1.2 Reference Concentration ( RfC) Determination . . . . . . . . . . . . . . . . . . . 8 3 8.2 Dose Response for Cancer Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3 8.2.1 Choice of Study/ Data With Rationale and Justification . . . . . . . . . . . . 8 3 9.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK FROM DRINKING WATER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1 9.1 Regulatory Determination for Chemicals on the CCL . . . . . . . . . . . . . . . . . . . . 9 1 9.1.1 Criteria for Regulatory Determination . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1 9.1.2 National Drinking Water Advisory Council Recommendations . . . . . . 9 2 9.2 Health Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2 9.2.1 Health Criterion Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3 9.2.2 Hazard Characterization and Mode of Action Implications . . . . . . . . . 9 3 ix Aldrin/ Dieldrin   February 2003 9.2.3 Dose Response Characterization and Implications in Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 6 9.3 Occurrence in Public Water Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 12 9.3.1 Occurrence Criterion Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 12 9.3.2 Monitoring Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 13 9.3.3 Use and Fate Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 16 9.4 Risk Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 17 9.4.1 Risk Criterion Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 17 9.4.2 Exposed Population Estimates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 17 9.4.3 Relative Source Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 19 9.4.4 Sensitive Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 20 9.5 Regulatory Determination Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 20 10.0 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1 Abbreviations and Acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A1 APPENDIX A: Round 2 Aldrin Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B1 APPENDIX B: Round 2 Dieldrin Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B2 x Aldrin/ Dieldrin   February 2003 LIST OF TABLES Table 2 1. Selected Chemical Physical Properties of Aldrin and Dieldrin . . . . . . . . . . . . . 2 3 Table 3 1. Aldrin Mobility in Soils Used to Grow Corn . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4 Table 4 1. Aldrin Detections in Stream Bed Sediments . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 Table 4 2. Summary Occurrence Statistics for Aldrin . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 12 Table 4 3. Dieldrin Detections and Concentrations in Streams and Ground Water . . . . . 4 21 Table 4 4. Dieldrin Detections and Concentrations in Sediments, Whole Fish, and Bivalves ( All Sites) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 22 Table 4 5. Summary Occurrence Statistics for Dieldrin . . . . . . . . . . . . . . . . . . . . . . . . . . 4 32 Table 5 1. Aldrin and Dieldrin in Domestic Food Items 1981 to 1992 . . . . . . . . . . . . . . . 5 2 Table 5 2. Aldrin Concentrations in San Francisco Bay Area Fish in 1994 . . . . . . . . . . . . 5 6 Table 5 3. Summary of General Population Exposures to Aldrin in Media Other than Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 15 Table 5 4. Summary of General Population Exposure to Dieldrin in Media Other than Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 16 Table 5 5. Summary of Subpopulation Exposures to Aldrin in Media Other than Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 16 Table 5 6. Summary of Subpopulation Exposures to Dieldrin in Media Other than Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 17 Table 6 1. Distribution of Dieldrin in Rats after 104 Weeks . . . . . . . . . . . . . . . . . . . . . . . 6 7 Table 6 2. Relative Tissue Levels of Dieldrin in the Rat Following a Single Oral Dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 8 Table 6 3. Trivial Chemical Names of Aldrin, Dieldrin and Their Metabolites . . . . . . . . 6 14 Table 9 1. Dose Response Information from Key Studies of Aldrin and Dieldrin Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 8 Table 9 2. Selected Summary Statistics for Occurrence of Aldrin and Dieldrin in Drinking Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 14 Table 9 3. National Population Estimates for Aldrin and Dieldrin Exposure via Drinking Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 18 xi Aldrin/ Dieldrin   February 2003 LIST OF FIGURES Figure 2 1. Aldrin Chemical Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1 Figure 2 2. Dieldrin Chemical Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2 Figure 3 1. Biodegradation Pathways for Aldrin and Dieldrin, With Particular Reference to Oceanic Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 8 Figure 3 2. Photochemical Transformations ( Principally Atmospheric) Reported for Aldrin and Dieldrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 9 Figure 4 1. Geographic Distribution of Cross Section States for Round 2 ( SDWIS/ FED) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 7 Figure 4 2. States With PWSs With Detections of Aldrin for All States With Data in SDWIS/ FED ( Round 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 14 Figure 4 3. Round 2 Cross Section States With PWSs With Detections of Aldrin ( Any PWSs With Results Greater than the Minimum Reporting Level [ MRL]; Above) and Concentrations Greater than the Health Reference Level ( HRL; Below) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 15 Figure 4 4. Geographic Distribution of Cross Section States for Round 2 ( SDWIS/ FED) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 26 Figure 4 5. States With PWSs With Detections of Dieldrin for All States With Data in SDWIS/ FED ( Round 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 33 Figure 4 6. Round 2 Cross Section States With PWSs With Detections of Dieldrin ( Any PWS With Results Greater than the Minimum Reporting Level [ MRL]; Above) and Concentrations Greater than the Health Reference Level ( HRL; Below) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 34 Figure 6 1. Distribution Scheme for Dieldrin Among Blood and Various Tissues in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4 Figure 6 2. Metabolites of Aldrin and Dieldrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 14 Figure 6 3. Proposed Principal Metabolic Pathways for Aldrin and Dieldrin . . . . . . . . . . 6 16 Figure 7 1. The Possible Mode of Action of Aldrin/ Dieldrin on Hepatocarcinogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 39 1 1 Aldrin/ Dieldrin   February 2003 1.0 EXECUTIVE SUMMARY The U. S. Environmental Protection Agency ( EPA) has prepared this Health Effects Support Document to assist in determining whether to establish a National Primary Drinking Water Regulation ( NPDWR) for aldrin and dieldrin. Case study reports of human exposures and laboratory studies with animals demonstrate that oral exposure to both of these compounds can cause various adverse systemic, neurological, reproductive/ developmental, immunological, and genotoxic effects. Although multiple bioassays have established aldrin and dieldrin as hepatocarcinogenic in several strains of mice, they are apparently not carcinogenic in rats, and several large epidemiology studies have failed to associate convincingly exposure to them with cancer in humans. While some of these effects occur only at moderate to high doses, others have been observed at doses lower than 0.1 mg/ kg bw/ day. Nonetheless, the relatively infrequent occurrences of aldrin/ dieldrin at very low concentrations indicated by monitoring data, coupled with the fact that they are no longer manufactured or used in this country, indicate that aldrin/ dieldrin concentrations of concern are unlikely to be found in public water systems. EPA will present a preliminary determination and further analysis in the Federal Register Notice covering the Contaminant Candidate List proposals.

Chemical Identities and Properties Aldrin ( CAS Registry Number [ RN] 309 00 2) is the most common name for the substance composed of at least 95% of the chemical 1,2,3,4,10,10 hexachloro 1,4,4a, 5,8,8ahexahydro exo 1,4 endo 5,8 dimethanonaphthalene. Technical grade aldrin contains at least 90% of this substance ( i. e., it has a main ingredient purity of at least 85.5%). Similarly, dieldrin ( CAS RN 60 51 1) refers to the substance composed of at least 85% of the chemical 1,2,3,4,10,10 hexachloro 6,7 epoxy 1,4,4a, 5,6,7,8,8a octahydro endo 1,4 exo 5,8 dimethanonaphthalene. Technical grade dieldrin contains at least 95% of this substance ( i. e., it has a main ingredient purity of at least 80.75%).

Dieldrin, a stereoisomer of endrin, was typically produced by the epoxidation of aldrin with peracetic or perbenzoic acid. In their " pure" formulations, both aldrin and dieldrin are composed of clear to white crystals with densities greater than water, and have both low volatilities and aqueous solubilities. Both are relatively stable in the presence of organic and inorganic alkalies and mild acids, slightly corrosive to metals upon storage, and compatible with most fertilizers and pesticides.

Aldrin/ Dieldrin Uses, Manufacture, and Environmental Fate Aldrin and dieldrin are synthetic organochlorine pesticides that act as effective contact and stomach poisons for insects. Originally, they were used as broad spectrum soil insecticides for the protection of various food crops, as seed dressings, to control infestations of pests like ants and termites, and to control several insect vectors of disease. In 1972, the EPA cancelled all but three specific uses of these compounds ( subsurface termite control, dipping of non food plant roots and tops, and completely contained moth proofing in manufacturing processes), which by 1987 were voluntarily cancelled by the manufacturer. Use of these compounds peaked in the 1 2 Aldrin/ Dieldrin   February 2003 U. S. during 1966 at 19 million lbs for aldrin and 1 million lbs for dieldrin. These compounds have not been produced domestically since 1974, and while some importation of aldrin began during that year, this ceased after 1985.

Total releases of aldrin/ dieldrin to the environment since 1987 are not known, but hazardous waste treatment facilities in three states ( AR, MI, TX) reported releases totaling 25,622 lbs in 1998, most of which was directly to land. Data from the Agency for Toxic Substances and Disease Registry ( ATSDR) indicate that these compounds have been detected in site samples from 40 different states; aldrin has been detected at National Priorities List ( NPL) hazardous waste sites in 31 states, while dieldrin has been found at NPL sites in 38 states.

Under most environmental conditions, aldrin is largely converted via biological and/ or abiotic mechanisms to dieldrin, which is significantly more persistent. Most environmental releases of aldrin and dieldrin are directly to soil. Because of low water solubility and tendency to bind strongly to soils, both compounds migrate downward very slowly through soils or into surface or ground water. Most surface water aldrin/ dieldrin has been attributed to particulate surface run off. Over time, it is possible that significant volatilization of aldrin/ dieldrin might occur, with subsequent atmospheric photodegradation and/ or rainfall " washout." Collectively, these characteristics will foster low levels of aldrin/ dieldrin water contamination over comparatively extended periods of time. Dieldrin's extreme apolarity results in a high affinity for organic matter such as animal fats and plant waxes, which could lead to its bioaccumulation in the food chain.

Exposure to Aldrin/ Dieldrin As neither aldrin nor dieldrin has been used in the U. S. since 1987, new releases to the environment should not occur. Only rare exceptions to this generalization might occur at hazardous waste treatment facilities. Over time, therefore, the frequency and magnitude of population exposure to aldrin/ dieldrin can be confidently expected to decline from those experienced to date ( 2001). Currently available sampling and monitoring data suggest that although potential exposures to aldrin/ dieldrin via drinking water could be of similar magnitude to those estimated from the diet, which exposures in turn are likely to be substantially higher than those from breathing air or ingesting soil, they are unlikely to occur at significant frequencies or dose levels.

The data analyzed in this document on the occurrence in drinking water of aldrin/ dieldrin were collected beginning in 1993 under " Round 2" of the Safe Drinking Water Act's Unregulated Contaminant Monitoring ( UCM) Program. Monitoring ended in January 1999, for small public water systems ( PWSs), and in January 2001, for large PWSs. These data, from 34 states and a number of Native American tribal systems, were not collected utilizing a uniform or adequate statistical framework, and were in some cases incomplete and/ or biased. To partially address the questionable representativeness of the combined data set, a " national cross section" of 20 Round 2 states ( AK, AR, CO, KY, ME, MD, MA, MI, MN, MS, NH, NM, NC, ND, OH, OK, OR, RI, TX, and WA) was selected. The procedure used to construct this " reasonable representation" of national occurrence evaluated the individual data sets for completeness, 1 3 Aldrin/ Dieldrin   February 2003 quality, bias, pollution potentials from manufacturing/ population density and from agricultural activity, and for " geographic coverage" in relation to all states. Because data from MA were incomplete and considered abnormal for synthetic organic compounds like aldrin/ dieldrin ( an atypically high percentage of detections in a relatively small number of PWSs), Round 2 crosssection occurrence data for aldrin/ dieldrin are discussed primarily in the context of the other 19 states.

The data indicate that each compound is only infrequently detected in PWSs, and then, generally, only at very low concentrations. With respect to the Health Reference Level ( HRL, a preliminary estimated health effect level used in these analyses) for these compounds of 0.002 : g/ L ( based on estimated excess lifetime cancer risks of 10 S 6), concentrations of aldrin and dieldrin greater than or equal to this level were detected in only 0.016 and 0.093% of the Round 2 cross section PWSs, respectively. These percentages extrapolate nationally to 11 PWSs serving 38,871 people for aldrin, and 61 PWSs serving 149,827 people for dieldrin. As a consequence of excluding states with positively biased detect statistics, Round 2 cross section data underestimate the national occurrence of these compounds in PWSs. It is important to remember that only one positive sample ( i. e., taken at a single time point from a single sampling location) was required to classify a PWS as one with aldrin or dieldrin detections   a practice that certainly overestimates population exposures.

Data from all the reporting Round 2 states may be used to derive more conservative, probably over estimates of the national PWS occurrences of aldrin and dieldrin at levels $ the HRL. These data yield respective PWS detection rates of 0.212 and 0.211%, which extrapolate nationally to 138 PWSs serving 1,051,989 people and 137 PWSs serving 792,703, respectively. Only five states ( AL, MA, NM, PA, TX) and eight states ( AL, AR, CT, MA, MD, NC, PA, TX) detected aldrin or dieldrin, respectively, in any PWS.

While the U. S. Geological Survey's National Ambient Water Quality Assessment ( NAWQA) Program did not analyze for the presence of aldrin in ambient ground or surface waters, it did analyze for samples of aquatic biota tissue and stream bed sediments taken from 591 sites located in significant watersheds and aquifers from 1992 to 1995. Aldrin was not detected in any of the aquatic biota samples, but was detected above the Method Detection Limit ( MDL) of 1 mg/ kg at 0.4% of the sites ( detections were confined to mixed land use and agricultural sites; there were no urban or forest rangeland detections). Similarly, dieldrin was detected above the 1 mg/ kg MDL at 13.7% of the same sites, as well as above the MDL of 5 mg/ kg in 28.6 and 6.4% of whole fish and bivalve samples, respectively. Unlike aldrin, dieldrin was an NAWQA analyte for ambient surface and ground waters from 1991 to 1996. At MDLs of 0.001 and 0.01 mg/ L, dieldrin was detected in 4.64 and 2.39%, respectively, of total stream surface water sites, and in 1.42 and 0.93%, respectively, of total ground water sites.

Relative source contribution analyses estimate that ratios of dietary to drinking water intake range from 1.7 to 3.8 for aldrin, and from 0.9 to 8.8 for dieldrin. Ratios were computed for the 70 kg adult and the 10 kg child consuming 2 L/ day or 1 L/ day, respectively, of drinking water, and utilized either the median or the 99th percentile concentrations of the Round 2 crosssection PWS samples ( detections only) for aldrin ( 0.58 or 0.69 : g/ L) and dieldrin ( 0.16 or 1.36 1 4 Aldrin/ Dieldrin   February 2003 : g/ L), as well as estimated adult and child total dietary intakes of aldrin ( 3.3 to 6.5 and 13 to 18 × 10! 5 mg/ kg bw/ day, respectively) and dieldrin ( 3.6 and 14 × 10! 5 mg/ kg bw/ day, respectively), which were based on data from the 1980s to early to mid 1990s.

These dietary/ drinking water intake ratios would be reduced by factors of approximately 3 to 6 under the very conservative approach of using median and 99th percentile detect concentrations based on monitoring data from all reporting UCM Round 2 states. Thus, drinking water appears capable of potentially providing a significant portion of the total daily dietary intake of aldrin/ dieldrin only when analyzed utilizing conservative assumptions, and then only for limited populations under unlikely exposure circumstances.

Even when using 30 year old air monitoring data that likely substantially overestimate current daily inhalation intakes of aldrin/ dieldrin, they are still relatively low ( 0.013 to 0.24 × 10 5) compared to dietary estimates and potentially possible ( although unlikely) exposures from drinking water. Similarly, data available for dieldrin suggest that ingestion of soil represents only a minor exposure pathway for aldrin/ dieldrin.

Toxicokinetics of Aldrin/ Dieldrin Few direct data were found in the literature on the absorption of aldrin/ dieldrin, especially in humans. Dose related increases in blood and adipose tissue levels of dieldrin were reported in volunteers exposed via diet to small amounts for 18 to 24 months, with concentrations in the blood equal to 8.6% of the amount ingested per day under steady state conditions. Inhalation studies using volunteers suggest that 20 to 50% of inhaled aldrin vapor may be absorbed and retained in the human body. One study in rats estimated that approximately 10% of an orally administered dose of aldrin was absorbed via the gastrointestinal tract. Other studies in rats have demonstrated that dieldrin concentrations in the blood and liver increase during the first 9 days of dietary exposure to 50 parts per million ( ppm), then remain fairly constant over the next 6 months; also, that absorption of aldrin and dieldrin is detected within 1 to 5 hours after oral dosing and occurs primarily via the hepatic portal vein instead of the thoracic lymph duct. Additionally, uptake of aldrin in isolated, perfused rabbit lungs was demonstrated to occur in a biphasic process of simple diffusion. Direct absorption of aldrin/ dieldrin through intact skin has been reported in rabbits, dogs, monkeys, and humans.

Because of its relatively rapid metabolic conversion to dieldrin, aldrin is infrequently observed in human tissue and there is little information on its distribution in human tissue. As a result of their hydrophobic nature, the highest concentrations of aldrin/ dieldrin and their metabolites are typically found in the adipose tissues of both humans and other animals. Based on several studies involving volunteers or human autopsies, the steady state relative distribution of dieldrin in whole blood, brain grey matter, brain white matter, liver, and adipose tissue is estimated to be 1, 2.8, 4.2, 22.7, and 136, respectively. The leanest individuals appear to have the highest adipose tissue concentration of dieldrin, but both the lowest total body burden of dieldrin and the lowest proportion of total exposure dose is retained in their adipose tissue. Blood levels of dieldrin do not increase during periods of surgical stress or complete fasting, and decline exponentially after termination of exposure, with considerable variation among 1 5 Aldrin/ Dieldrin   February 2003 individuals ( mean half lives of 266 and 369 days were reported in 2 studies). Placental transfer of dieldrin can occur, resulting in fetal blood concentrations higher than those in maternal blood ( 1.22 vs. 0.53 mg/ kg, respectively).

Distribution studies conducted in animals ( rats, mice, guinea pigs, dogs, primates, and various domesticated species) generally support the findings from human studies, at least qualitatively. Exposure to aldrin/ dieldrin leads to preferential disposition of dieldrin ( and metabolites) in adipose tissue, with lesser to very small amounts variously reported in liver, kidney, brain, muscle, lung, blood, and certain other tissues. In partial summary, there are some differences in distribution parameters among species and, at least in rodents, between sexes ( females reportedly absorb and retain more dieldrin in their adipose tissue and most organs than do males); blood concentrations appear to decline more rapidly upon termination of exposure in animals than in humans; redistribution of dieldrin from the liver to adipose tissue may occur principally via the lymphatic system; transplacental transfer of dieldrin has also been demonstrated in rodents; and the available animal data collectively suggest that distribution patterns of aldrin and dieldrin will be similar for most routes of exposure.

As noted previously, in many organisms the initial and principal biotransformation of aldrin following oral exposure is the relatively rapid, mixed function oxidase mediated epoxidation to dieldrin. Also referred to as aldrin epoxidase, these enzymes are prominent in the endoplasmic reticulum of vertebrate hepatocytes. Male rats and mice appear to convert more rapidly and extensively than do females. In some extra hepatic tissues ( e. g., lung) that contain relatively little cytochrome P 450 activity, in vitro studies suggest that aldrin may be epoxidized to dieldrin via an alternate, prostaglandin endoperoxide synthase pathway, one which is dependent on arachidonic acid rather than on nicotine adenine dinucleotide phosphate ( NADPH). Additionally, several in vivo and in vitro animal studies have demonstrated the dermal conversion of aldrin to dieldrin. Although data from humans are extremely sparse, one excretion study conducted on workers occupationally exposed to aldrin/ dieldrin identified 9 hydroxy dieldrin as a fecal metabolite. Animal studies have collectively demonstrated the following metabolites of dieldrin to be among the most significant: pentachloroketone, 6,7 transdihydroxydihydroaldrin and its glucuronide conjugate, 9 hydroxy dieldrin and its glucuronide conjugate, and aldrin dicarboxylic acid. The appearance and proportions of these metabolites can vary by species, strain, and sex, as can the overall rates of aldrin/ dieldrin biotransformation.

Limited data from occupational and volunteer studies suggest that in humans, excretion of aldrin/ dieldrin and most of their metabolites occurs primarily through the bile and feces, with smaller amounts appearing in the urine. In addition, nursing mothers have been found to excrete dieldrin via lactation. Similar findings are observed in most animals, although in rabbits urinary excretion exceeds fecal excretion. Again, the identity and relative amounts of fecal and urinary excretion products can vary somewhat among species ( e. g., pentachloroketone was identified as a significant urinary metabolite in the CFE rat, but was not detected in the CF 1 mouse), as well as between sexes ( biliary/ fecal and urinary excretion following exposure to radiolabeled dieldrin was found to be higher in male than in female rats). 1 6 Aldrin/ Dieldrin   February 2003 Adverse Effects from Exposure to Aldrin/ Dieldrin Data from the available literature indicate that oral exposure to aldrin/ dieldrin can induce a range of adverse systemic, neurological, reproductive/ developmental, immunological, genotoxic, and tumorigenic effects in humans and/ or animals. Some of these effects are manifested only at moderate to relatively high doses, but others have been observed at doses lower than 0.1 mg/ kg bw/ day.

In humans, acute exposures to high concentrations of aldrin/ dieldrin result most notably in toxicity to the central nervous system; effects most commonly reported include hyperirritability, convulsions, and coma, sometimes followed by cardiovascular sequelae such as tachycardia and elevated blood pressure. Persistent headache, nausea and/ or vomiting, shortterm memory loss, hypothermia, and abnormal electroencephalogram patterns have also been observed. For adult males, the acute oral lethal dose ( LD 50) for both compounds has been estimated to be 5 g, or about 70 mg/ kg bw.

When humans have been exposed for longer periods to lower doses of these compounds, neurotoxic symptoms have included headache, dizziness, general malaise, nausea, vomiting, and muscle twitching or myoclonic jerking. In general, occupational studies indicate that exposure to aldrin/ dieldrin does not result in adverse hematological or immunological ( e. g., dermal sensitization) effects in humans. However, two cases of immunohemolytic anemia have been linked to dieldrin exposure, as have several instances of aplastic anemia to aldrin/ dieldrin exposure. While some of these associations appear fairly suggestive, others are more problematic.

The available literature does not include other significant adverse health effects in humans resulting from longer term or chronic exposure to aldrin/ dieldrin. With the exception of several statistically significant increases in the incidence of rectal or liver/ biliary cancer that generally disappeared in follow up studies, a variety of occupational/ epidemiology studies have failed to provide convincing evidence that exposure to aldrin/ dieldrin results in elevated risks of either cancerous or noncancerous disease. When standardized mortality ratios of exposed vs. general populations were computed for both specific causes and all causes of death, virtually all were lower than 1.0 in both initial and follow up reports.

Available animal data ( mouse, rat, guinea pig, rabbit, and dog) indicate oral LD 50 values ranging from 33 to 95 mg/ kg bw. Similar to those described in humans, neurotoxic effects observed in animals following acute to chronic exposure to aldrin/ dieldrin include increased irritability, salivation, hyperexcitability, tremors followed by convulsions, loss of body weight, depression, prostrations, and death. Convulsions were observed in the rat after exposure to aldrin for 3 days at 10 mg/ kg bw/ day, as was brain cell histopathology after a 6 month exposure to 2.75 mg/ kg bw/ day in rats, or a 9 month exposure to 0.89 mg/ kg bw/ day in dogs. Chronic exposure of rats and mice to 0.45 to 1.5 mg aldrin/ kg bw/ day has variously resulted in hyperexcitability, tremors, and clonic convulsions. 1 7 Aldrin/ Dieldrin   February 2003 Single doses of 0.5 to 16.7 mg dieldrin/ kg bw were reported to disrupt operant behavior in the rat, and three 2 to 4 month rat studies collectively demonstrated hyperexcitability, tremors, and impaired operant behavior at Lowest Observed Adverse Effect Levels ( LOAELs) of 2.5, 0.5, or 0.025 mg dieldrin/ kg bw/ day, respectively. Various long term ( 80 weeks to 29 months) rat studies collectively reported hyperexcitability, irritability, tremors, and/ or convulsions at LOAELs of 0.5 to 2.5 mg dieldrin/ kg bw/ day. In another 2 year study in rats that had several potential limitations, cerebral edema and small degenerative foci were found at doses as low as 0.0016 mg dieldrin/ kg bw/ day. In one 2 year study in dogs, convulsions were observed at 0.5 mg dieldrin/ kg bw/ day, while another reported normal electroencephalograms at 0.05 mg dieldrin/ kg bw/ day.

In a number of short to intermediate term studies in rats and mice, various manifestations of hepatotoxicity ( increased relative liver weight, liver enlargement, hepatocyte hypertrophy, and elevated DNA synthesis; induction of mixed function oxidases, increased size and number of focal lesions in the rat, but not the mouse, following pretreatment with diethyl nitrosamine) were associated with LOAELs ranging from 0.5 to 1.5 mg dieldrin/ kg bw/ day, and No Observed Adverse Effect Levels ( NOAELs) ranging from 0.15 to 0.5 mg dieldrin/ kg bw/ day. One 7 to 10 day mouse study reported elevated relative liver weights at doses as low as 0.015 mg dieldrin/ kg bw/ day ( a NOAEL was not determined).

One longer term ( 16 month) study in dogs reported increased absolute and relative liver weights and hepatic fatty degeneration at doses of 0.12 to 0.25 mg aldrin/ kg bw/ day, but not 0.043 to 0.091 mg aldrin/ kg bw/ day; however, no signs of hepatotoxicity were reported in another 25 month study in dogs at 0.5 mg aldrin/ kg bw/ day. Liver histopathology was observed in one 2 year rat study at 0.025 mg aldrin/ kg bw/ day, as were enlarged livers at 2.5 mg aldrin/ kg bw/ day; nondose related liver histopathology was also seen at 1 mg aldrin/ kg bw/ day, and increased relative liver weights at 1.5 mg/ kg bw/ day, in a second long term ( 31 month) study in rats. However, hepatotoxicity was not noted in several other long term studies in the mouse, rat, or dog. Similarly, while several long term studies of dieldrin in the rat, mouse, or dog did not report evidence of hepatotoxicity, increased absolute and/ or relative liver weights, increased serum alkaline phosphatase activity, and liver histopathology were collectively observed in three other 2 year studies ( two rat, one dog) at 0.025 to 0.05 mg aldrin/ kg bw/ day.

There are limited animal data to suggest that aldrin/ dieldrin can induce nephropathy or exacerbate pre existing nephropathy. One 2 year study in rats reported that nephritis and distended hemorrhagic urinary bladders were associated with a LOAEL of 2.5 mg aldrin/ kg bw/ day and a NOAEL of 0.5 mg aldrin/ kg bw/ day. Exposures to 0.043 to 0.091 mg aldrin/ kg bw/ day for up to 16 months were reported to cause distal renal tubule vacuolation in female dogs, and in dogs of both sexes at 0.12 to 0.25 mg/ kg bw/ day. Chronic exposure to 5.0 and 7.5 mg dieldrin/ kg bw/ day has been reported to result in the development of hemorrhagic and/ or distended urinary bladders in male rats, usually accompanied by substantial nephritis.

In general, animal studies have provided only mixed data that moderate to relatively high doses of aldrin/ dieldrin can result in adverse reproductive or developmental effects. There are 1 8 Aldrin/ Dieldrin   February 2003 some in vivo and in vitro data to suggest that these compounds may be weak endocrine disruptors, as various effects on male and female hormone levels and/ or receptor binding, estrus cycle, endometrial or breast cell proliferation, and male germ cell degeneration and interstitial testicular cell ultrastructure have been reported. A 5 day exposure of male mice to 1 mg aldrin/ kg bw/ day failed to produce unequivocal evidence of dominant lethality, and a single exposure of male mice to 50 mg dieldrin/ kg bw did not produce a significant dominant lethal effect.

Among the effects noted in several studies in rats and dogs at aldrin doses of 0.125 to 0.3 mg/ kg bw/ day were reduced pup survival during lactation, failure to achieve estrous in some females, impaired mammary development and milk production, and depressed sexual drive in males; initially, reduced fertility was also observed in two 3 generation rat studies at doses of 0.625 to 1.38 mg aldrin/ kg bw/ day.

Similarly, several studies using rats, mice, or dogs have demonstrated that dieldrin doses of 0.125 to 0.75 mg/ kg bw/ day can result in reduced pup survival during lactation. Dieldrin doses of 0.125 to 0.275 mg/ kg bw/ day have also resulted in initially reduced parental generation fertility rates in 3 generation rat studies. Another limited rat study reported various neural lesions in pups born to dams dosed with as little as 0.004 to 0.008 mg dieldrin/ kg bw/ day. Exposure to dieldrin doses of 4 mg/ kg bw/ day ( gestation day [ gd] 15 to postpartum day [ ppd] 21) or 6 mg/ kg bw/ day ( gd 7 to 16) did not affect fecundity, stillbirth or terata frequencies, fetotoxicity, or perinatal mortality in two studies in rats. However, teratogenic responses ( webbed foot, cleft palate, open eye) were observed in mice and hamsters after dieldrin exposures of 15 mg/ kg bw/ day ( gd 9) or 30 mg/ kg bw/ day ( gd 7 to 9), respectively. Another study in mice noted an increase in supernumerary ribs, but not in major malformations, after a dieldrin exposure of 3 mg/ kg bw/ day ( gd 7 to 16).

With respect to the immunotoxicity of aldrin/ dieldrin, several studies in mice suggest that exposure to dieldrin may induce immunosuppression: single oral doses of $ 18 mg/ kg bw have reportedly decreased the antigenic response to mouse hepatitis virus 3; a 10 week dietary exposure to concentrations as low as 1 ppm ( 0.15 mg/ kg bw/ day) increased the lethality of Plasmodium berghei or Leishmania tropica infections; and 3, 6, or 18 weeks of dietary exposure to concentrations as low as 1 ppm ( 0.15 mg/ kg bw/ day) were found to decrease tumor cell killing ability.

Numerous long term bioassays have convincingly demonstrated that aldrin and dieldrin are hepatocarcinogens in several strains of mice; in one of these studies dieldrin was also judged to have induced lung, lymphoid, and " other" tumors. Increased incidences of hepatocellular carcinoma and/ or adenoma in mice have been reported for doses as low as 0.6 to 1.5 mg aldrin/ kg bw/ day and 0.375 to 1.5 mg dieldrin/ kg bw/ day. In one dieldrin study, however, dose related increases in the incidence of hepatocellular carcinoma and combined liver tumors, as well as decreases in tumor latency, began at doses as low as 0.015 mg/ kg bw/ day. In contrast to these results, all of the available bioassays ( some of which are now considered inadequate tests of carcinogenicity) have failed to demonstrate any evidence of liver tumorigenicity in any strain of rats that was tested. Further, only a single rat bioassay of aldrin gave any evidence of 1 9 Aldrin/ Dieldrin   February 2003 tumorigenicity at any site   evidence for increased incidences of thyroid follicular cell adenoma/ carcinoma in males and females and adrenal cortex adenoma/ carcinoma in females, increases which have been considered equivocal/ suggestive by some, and unrelated to treatment by others. As noted previously, aldrin/ dieldrin's carcinogenicity has, on balance, not been demonstrated in humans.

Much remains unknown about the modes of action that may underlie the various toxic effects produced by exposure to aldrin/ dieldrin. The hyperexcitability associated with aldrin/ dieldrin neurotoxicity may arise from enhancement of synaptic activity throughout the central nervous system ( CNS), but it is not clear whether it results from facilitated neurotransmitter release at the nerve terminals or from reducing the activity of inhibitory neurotransmitters within the CNS. One hypothesis suggests that dieldrin may act by inhibiting calcium dependent brain ATPases, which would inhibit the cellular efflux of calcium and result in higher intracellular calcium levels and subsequent neurotransmitter release. Data from relatively recent studies indicate that aldrin/ dieldrin's principal mode of neurotoxic action likely involves their role as antagonists of the membrane receptor for the inhibitory neurotransmitter, gamma aminobutyric acid ( GABA), and blocking the influx of chloride ion through the GABA A receptor ionophore complex. Further, an in vitro study using fetal rat brain cells suggests that dieldrin may have an even greater functional effect on dopaminergic neurons.

From the available studies, the carcinogenic potential of aldrin/ dieldrin appears largely confined to the mouse, and it may not rest predominantly on genotoxicity modes of action. This appears most evident in the general failure of aldrin/ dieldrin to induce gene point mutations ( 28 negative assays, 3 positive). However, when considering either direct DNA damage or chromosome related interactions ( aberrations, aneuploidy, SCEs), the assay results are significantly more balanced ( 15 negative, 2 most likely negative, 11 positive, 4 " questionably" positive).

Aldrin/ dieldrin's capacity to inhibit various forms of in vitro intercellular communication in both human and animal cells may represent a significant " epigenetic" mode of carcinogenic action with respect to their in vivo effects on tumor production. Several recent studies suggest that the mouse specific hepatocarcinogenic effects of aldrin/ dieldrin may result from the induction of intracellular oxidative stress ( via the generation of reactive oxygen species that result in oxidative damage to DNA, protein, and lipid macromolecules), as well as increased hepatic DNA synthesis. These effects generally occur after aldrin/ dieldrin treatment in mice, but not in rats. After observing the frequency and patterns of c Ha ras proto oncogene mutations appearing in the DNA of glucose 6 phosphatase deficient hepatic lesions found in control mice, or in those treated with dieldrin or phenobarbital, another study concluded that the increase in hepatic lesions ( and thus tumors) resulting from dieldrin treatment principally resulted from promotional, rather than initiation, events. It also has been postulated that aldrin/ dieldrin induction of hepatic DNA synthesis may result from the modulation of protooncogene expression via various transcription factors.

The available literature included almost no direct evidence for any human subpopulations that would be particularly sensitive to the toxic effects of aldrin/ dieldrin, or for which relevant 1 10 Aldrin/ Dieldrin   February 2003 toxicokinetics are known to differ significantly from those for the general population. Speculatively, the fetus and very young children might be at increased risk from exposures to aldrin/ dieldrin as a result of immature hepatic detoxification and excretion functions, as well as developing target organ systems. In this regard, a single case study reported that a 3 year old female child died after ingesting approximately 8.2 mg aldrin/ kg bw, which is roughly an order of magnitude below the estimated lethal dose for adult males. Several mechanistic studies that describe the prenatal effects of aldrin/ dieldrin on GABA receptor malfunctions and on subsequent behavioral impairment also suggest an increased sensitivity of children. Declining organ and immune functions could potentially render the elderly more susceptible to aldrin/ dieldrin toxicity, and it is reasonable to expect that any individuals with compromised liver, immune, or neurological functions ( as a result of disease, genetic predisposition or toxic insult) might be especially sensitive to these compounds.

Dose Response Assessments As previously noted, the acute oral lethal dose for aldrin/ dieldrin in adult humans has been estimated at 70 mg/ kg bw, which is about 3 times the dose reported to have induced convulsions within 20 minutes of ingestion. Oral LD 50 values in various animal species for the two compounds have been reported to range from 33 to 95 mg/ kg bw, and may be affected by age at the time of exposure. In rats, LD 50 values were reported at 37 mg/ kg bw for young adults, 25 mg/ kg bw for 2 week old pups, and 168 mg/ kg bw for newborns.

Adequate dose response relationships have not been characterized in humans for any of the toxic effects of aldrin/ dieldrin. In animals, oral exposure has produced a variety of dosedependent systemic, neurological, immunological, endocrine, reproductive, developmental, genotoxic, and tumorigenic effects over a collective dose range of at least three orders of magnitude (< 0.05 to 50 mg/ kg bw), depending on endpoint and exposure duration. For noncancer effects, the U. S. EPA has determined oral Reference Doses ( RfDs) for both aldrin and dieldrin based on the most sensitive relevant toxic effects ( critical effects) reported. For aldrin, the critical effect was liver toxicity observed in one rat study after chronic exposure to approximately 0.025 mg/ kg bw/ day, the LOAEL and the lowest dose tested. This dose was divided by a composite uncertainty factor of 1,000 ( to account for rat to human extrapolation, potentially sensitive human subpopulations, and the use of a LOAEL rather than a NOAEL) to yield an oral RfD of 3 × 10 5 mg/ kg bw/ day. Similarly, for dieldrin a chronic rat NOAEL for liver toxicity of approximately 0.005 mg/ kg bw/ day was divided by a composite uncertainty factor of 100 ( to account for rat to human extrapolation and potentially sensitive human subpopulations), yielding an oral RfD of 5 × 10 5 mg/ kg bw/ day.

Based on long term mouse bioassays, the EPA has classified both aldrin and dieldrin as Group B2 carcinogens under the 1986 cancer guidelines, that is, as probable human carcinogens with little or no evidence of carcinogenicity in humans, and sufficient evidence in animals. Under the U. S. EPA's proposed 1996/ 1999 cancer risk assessment guidelines, the weight of evidence indicates that aldrin and dieldrin could be classified as rodent carcinogens that are " likely to be carcinogenic to humans by the oral route of exposure, but whose carcinogenic potential by the inhalation and dermal routes of exposure cannot be determined because there 1 11 Aldrin/ Dieldrin   February 2003 are inadequate data to perform an assessment." This characterization must be tempered by the lack of evidence for significant human carcinogenicity from epidemiological studies and by the general lack of corroborative evidence for carcinogenicity in rats. Mechanistic studies suggest that non genotoxic modes of action may underlie or contribute to aldrin/ dieldrin's carcinogenic potential, but their relevance to human carcinogenicity is not fully established, and a role for genotoxic mechanisms cannot confidently be eliminated based on the available data. Based on these considerations, the quantitative cancer risk assessments of aldrin and dieldrin have been conducted conservatively using the linear default model.

This approach has yielded respective geometric mean cancer potency estimates for aldrin and dieldrin of 17 and 16 ( mg/ kg bw/ day) 1. These result in drinking water unit risks of 4.9 × 10 4 per mg/ L and 4.6 × 10 4 per mg/ L, respectively. For both compounds, an estimated lifetime excess cancer risk of 10 6 results from a drinking water concentration of 0.002 : g/ L . This concentration, 0.002 : g/ L, was selected as the Health Reference Level ( HRL) used elsewhere in this document to put into context the levels of aldrin/ dieldrin detected in drinking water.

Risk Characterizations and Regulatory Determinations for Aldrin/ Dieldrin Evaluating the second criterion involves analysis of public water system monitoring data, ambient water concentrations and environmental releases, and the chemical's environmental fate. Since aldrin/ dieldrin have not been used in the U. S. since 1987, no new environmental releases are expected ( with the possible exception of a very few from hazardous waste treatment plants). Available data indicate that these chemicals are detected very infrequently in drinking water, and then at very low concentrations. Their occurrence in ambient water appears to be of minimal concern, and while environmental fate data suggest that they may continue to be released to water over a long period of time, the concentrations involved will remain quite low. 2 1 Aldrin/ Dieldrin   February 2003 2.0 IDENTITY: PHYSICAL AND CHEMICAL PROPERTIES Figure 2 1. Aldrin Chemical Structure The molecular weight and chemical formula of aldrin ( CAS RN 309 00 2) are shown above ( Figure 2 1), in conjunction with two representations of its structural formula. Aldrin is the common name approved by the International Standards Organization ( except in Canada, Denmark, and the former Soviet Union) for the product that contains at least 95% of the substance identified by one of the following IUPAC chemical names ( IARC, 1974a; IPCS, 1989a, b; Lewis, 1993):

1,2,3,4,10,10 hexachloro 1,4,4a, 5,8,8a hexahydro exo 1,4 endo 5,8 dimethanonaphthalene; or ( 1R, 4S, 5S, 8R) 1,2,3,4,10,10 hexachloro 1,4,4a, 5,8,8a hexahydro 1,4: 5,8 dimethanonaphthalene In Canada, aldrin refers to the pure compound, which in Great Britain is called HHDN. Aldrin has a significant number of chemical synonyms and common trade names ( HSDB, 2000a; IARC, 1974a; IPCS, 1989a, b; Sittig, 1991; USEPA, 1992), including:

ALDOCIT Aldrex ALDROSOL Compound 118 Drinox ENT 15,949 Hexachlorohexahydro endo exo dimethanonaphthalene HHDN KORTOFIN OCTALENE OMS 194 SEEDRIN 2 2 Aldrin/ Dieldrin   February 2003 Technical grade aldrin was formulated to contain not less than 90% aldrin ( as defined above), i. e., not less than 85.5% of the main ingredient, with not less than 4.5% insecticidal impurities and not more than 10% other impurities ( HSDB, 2000a; IARC, 1974a; IPCS, 1989a, b). Impurities that have been identified include a complex mixture of compounds formed by the polymerization of hexachlorocyclopentadiene ( HCCPD) and bicycloheptadiene ( BCH) ( 3.6 to 3.7%), polychlorohexahydrodimethanonaphthalene compounds ( isodrin) ( 3.5%), hexachlorobutadiene ( 0.5 to 0.6%), chlordane ( 0.5%), octachlorocyclopentene ( 0.4 to 0.5%), toluene ( 0.3 to 0.6%), HCCPD ( 0.2%), HHDN di adduct ( 0.1%), BCH (< 0.1%), and hexachloroethane (< 0.1%) ( IARC, 1974a; IPCS, 1989a, b).

Aldrin has been formulated into seed dressings ( 75%), dust concentrates ( 75%), emulsifiable concentrates ( 24 to 48%), wettable powders ( 20 to 40%), granules ( 2 to 25%), lowpercentage dusts ( 2 to 5%), and mixtures with fertilizers ( 0.4 to 2%) ( HSDB, 2000a; IARC, 1974a). Epichlorohydrin, a known carcinogen, was sometimes incorporated into the emulsions to help prevent corrosion by hydrochloric acid, as was urea into wettable powders to prevent dehydrochlorination by certain catalytically active carriers ( HSDB, 2000a).

Aldrin is reported to be stable in the presence of organic and inorganic alkalies, diluted acids, and hydrated metal chlorides ( Budavari et al., 1989; IARC, 1974a; Lewis, 1993). While minimally corrosive to steel, brass, monel, copper, nickel, and aluminum, aldrin can be slightly corrosive to metals upon storage as a result of the slow formation of hydrogen chloride ( HSDB, 2000a; IPCS, 1989b). Most fertilizers, herbicides, fungicides, and insecticides were reported to be compatible with aldrin ( Lewis, 1993), but in general, contact with concentrated mineral acids, acid catalysts, acid oxidizing agents, phenols, or active metals should be avoided ( IPCS, 1989a, b; Sittig, 1991).

Figure 2 2. Dieldrin Chemical Structure Dieldrin is formed by the epoxidation of aldrin with peracetic or perbenzoic acid ( IARC, 1974a). Some of aldrin's chemical properties are summarized later in Table 2 1. 2 3 Aldrin/ Dieldrin   February 2003 Table 2 1. Selected Chemical Physical Properties of Aldrin and Dieldrin1 Property Aldrin Dieldrin Chem. Formula ( MW) C 12 H 8 Cl 6 ( 364.93) C 12 H 8 Cl 6 O ( 380.93)

Physical State Clear to white crystals; tan to dark brown solid ( technical) Clear to white crystals; buff to light tan flakes ( technical)

Melting Point 104! 105.5 ° C; 49! 60 ° C ( technical) 175! 177 ° C; > 95 ° C ( technical)

Boiling Point 145 ° C ( at 2 mm Hg) 330 ° C Density ( at 20 ° C) 1.6! 1.7 g/ cc; 1.54 g/ cc ( technical) 1.75 g/ cc; 1.62 g/ cc ( technical)

Solubility ( Water) 0.027 mg/ L ( at 27 ° C); also reported as 0.20 mg/ L ( at 25 ° C) 0.1! 0.195 mg/ L ( at 20! 29 ° C)

Solubility ( Organic Solvents) Moderately to very sol. in most paraf finic and aromatic hydrocarbons, esters, ketones, and halogenated solvents, less so in alcohols; > 600 g/ L in acetone, benzene, and xylene ( at 27 ° C) Moderately sol. in common organic solvents, except aliphatic petroleum hydrocarbons, and methanol ( in g/ L at 20 ° C: 400 ! benzene, 220 ! acetone, 10 ! methanol)

Log K ow 3.01 or 6.50; 7.4 ( technical) 5.40; 6.2 ( technical)

Log K oc 4.96 3.87 Vapor Pressure ( 20 ° C) 2.3! 7.5 x 10! 5 mm Hg 3.1 x 10 ! 6 or 1.78 x 10! 7 mm Hg Vapor Pressure ( 25 ° C) 1.4 x 10! 4 mm Hg or 6 x 10! 6 mm Hg 5.89 x 10! 6, 7.78 x 10! 7, or 1.8 x 10! 7 mm Hg Henry's Law Constant ( at 25 ° C) 3.2 x 10! 4 atm m3/ mol or 1.27 x 10! 5 atm m3/ mol ( est.) 5.8 x 10! 5 atm m3/ mol or 1.51 x 10! 5 atm m3/ mol Odor Mild chemical odor Mild chemical odor Odor Threshold 0.017 mg/ L ( water) 0.3 mg/ m3 ( air) 0.04 mg/ L ( water) NA ( air)

Conversion Factors2 ( at 25 ° C, 1 atm) 1 ppm = 14.96 mg/ m3 ( at 25 ° C, 1 atm) 1 ppm = 15.61 mg/ m3 ( at 25 ° C, 1 atm)

1 ATSDR ( 2000); Budavari et al. ( 1989); HSDB ( 2000a, b); IARC ( 1974a, b); IPCS ( 1989b); Lewis ( 1993); Sittig ( 1991); Verschueren ( 1983). 2 ATSDR ( 2000). 2 4 Aldrin/ Dieldrin   February 2003 The molecular weight and chemical formula of dieldrin ( CAS RN 60 57 1) are shown above ( Figure 2 2), in conjunction with two representations of its structural formula. Dieldrin is the common name approved by the International Standards Organization ( except in Canada, Denmark, and the former Soviet Union) for the product that contains at least 85% of the substance identified by one of the following IUPAC chemical names ( IARC, 1974b; IPCS, 1989a, b; Lewis, 1993):

1,2,3,4,10,10 hexachloro 6,7 epoxy 1,4,4a, 5,6,7,8,8a octahydro endo 1,4 exo 5,8 dimethanonaphthalene; or ( 1R, 4S, 5S, 8R) 1,2,3,4,10,10 hexachloro 1,4,4a, 5,6,7,8,8a octahydro 6,7 epoxy 1,4: 5,8 dimethanonaphthalene In Canada, dieldrin refers to the pure compound, which in Great Britain is called HEOD. Dieldrin has a significant number of chemical synonyms and common trade names ( HSDB, 2000b; IARC, 1974b; IPCS, 1989a, b; Sittig, 1991; USEPA, 1988), including:

ALVIT Compound 497 DIELDREX DIELMOTH ENT 16,225 HEOD Hexachloroexpoxyoctahydro endo exo dimethanonaphthalene Illoxol Octalux OMS 18 QUINTOX Red Shield TERMITOX Technical grade dieldrin was formulated to contain not less than 95% dieldrin ( as defined above), i. e., not less than 80.75% of the main ingredient; however, it was available in the United States in a formulation containing 100% active ingredient, i. e., not less than 85% HEOD, with not less than 15% related insecticidally active compounds ( HSDB, 2000b; IARC, 1974a; IPCS, 1989a, b; Lewis, 1993). Impurities reportedly found in technical grade dieldrin include aldrin, other polychloroepoxyoctahydrodimethanonaphthalenes ( including endrin, 3.5%), free HCl (< 0.4%), and water (< 0.1%) ( HSDB, 2000b; IARC, 1974b; IPCS, 1989a, b).

Dieldrin has been formulated into wettable powders ( 40 to 75%), oil solutions ( 18 to 20%), emulsifiable concentrates ( 15 to 20%), granules ( 5%), seed dressings, dusts, and mixtures with fertilizers ( HSDB, 2000b; IARC, 1974b).

Dieldrin is reported to be stable in the presence of organic and inorganic alkalies, mild acids commonly used in agriculture, and light ( Budavari et al., 1989; IARC, 1974b; IPCS, 1989a, b), although it may react with sunlight to produce photodieldrin ( IARC, 1974b). As with 2 5 Aldrin/ Dieldrin   February 2003 aldrin, dieldrin can be slightly corrosive to metals upon storage as a result of the slow formation of hydrogen chloride ( HSDB, 2000b; IPCS, 1989b). Most fertilizers, herbicides, fungicides, and insecticides were reported to be compatible with dieldrin ( Lewis, 1993), but in general, contact with concentrated mineral acids, acid catalysts, acid oxidizing agents, phenols, or active metals ( iron, copper, sodium) should be avoided ( Budavari et al., 1989; IPCS, 1989a, b; Sittig, 1991). Dieldrin is formed by the epoxidation of aldrin with peracetic or perbenzoic acid ( IARC, 1974a, b), and is a stereoisomer of endrin ( Budavari et al., 1989). It reportedly reacts with hydrogen bromide to give the bromohydrin ( HSDB, 2000b). Some of dieldrin's chemical properties are summarized in Table 2 1. 2 6 Aldrin/ Dieldrin   February 2003 References ATSDR. 2000. Agency for Toxic Substances and Disease Registry. Toxicological profile for aldrin/ dieldrin ( Update). Draft for public comment. Atlanta, GA: US Dept. of Health and Human Services, Public Health Service, ATSDR.

Budavari, S, M. J. O'Neil, A. Smith, and P. E. Heckelman ( eds.). The Merck index, 11th ed. Rahway, NJ: Merck & Co., Inc., pp. 223, 490.

HSDB. 2000a. Hazardous Substances Data Bank. Aldrin. Retrieved Sep. 20, 2000. Bethesda, MD: National Library of Medicine, Specialized Information Services Division, Toxicology and Environmental Health Information Program, TOXNET.

HSDB. 2000b. Hazardous Substances Data Bank. Dieldrin. Retrieved Sep. 20, 2000. Bethesda, MD: National Library of Medicine, Specialized Information Services Division, Toxicology and Environmental Health Information Program, TOXNET.

IARC. 1974a. International Agency for Research on Cancer. Evaluation of the carcinogenic risk of chemicals to humans. Aldrin. Lyon, France: IARC Monograph 5: 25 38.

IARC. 1974b. International Agency for Research on Cancer. Evaluation of the carcinogenic risk of chemicals to humans. Dieldrin. Lyon, France: IARC Monograph 5: 125 156.

IPCS. 1989a. International Programme on Chemical Safety. Aldrin and dieldrin health and safety guide. Health and safety guide no. 21. Geneva, Switzerland: World Health Organization, IPCS.

IPCS. 1989b. International Programme on Chemical Safety. Aldrin and dieldrin. Environmental health criteria 91. Geneva, Switzerland: World Health Organization, IPCS.

Lewis, Sr., R. J. 1993. Hawley's condensed chemical dictionary, 12th ed. New York, NY: Van Nostrand Reinhold Company, pp. 32, 387.

Sittig, M. 1991. Handbook of toxic and hazardous chemicals and carcinogens, 3rd ed., vol. 1. Park Ridge, NJ: Noyes Publications, pp. 6 64, 598 601.

USEPA. 1992. US Environmental Protection Agency. Aldrin drinking water health advisory. Washington, DC: USEPA Office of Water.

USEPA. 1988. US Environmental Protection Agency. Dieldrin health advisory. Washington, DC: USEPA Office of Water.

Verschueren, K. 1983. Handbook of environmental data on organic chemicals, 2nd ed. New York, NY: Van Nostrand Reinhold, pp. 168 173, 513 518. 3 1 Aldrin/ Dieldrin   February 2003 3.0 USES AND ENVIRONMENTAL FATE This section summarizes information derived from cited secondary references pertaining to the uses, manufacture, and environmental fate of aldrin and dieldrin.

3.1 Uses and Manufacture These compounds are organochlorine pesticides that act as highly effective contact and stomach poisons for insects ( IPCS, 1989a). Aldrin was used as a broad spectrum soil insecticide ( generally at 0.5 to 5 kg/ hectare) for the protection of corn, potato, citrus, and other crops against termites, corn rootworms, seed corn beetles and maggots, wireworms, rice water weevil, grasshoppers, Japanese beetles, etc., as well as a seed dressing for rice and to combat ant and termite infestations of wooden structures ( ATSDR, 2000; IPCS, 1989a, b; USEPA, 1992). Dieldrin was once used similarly in agriculture, but no longer; it was then used principally to protect wooden structures against ant and termite attack, in industry for protection against termites, wood borers and textile pests, and as a residual spray and larvacide for the control of several insect vectors of disease ( ATSDR, 2000; IPCS, 1989a, b; USEPA, 1988).

The US Department of Agriculture banned all uses of aldrin and dieldrin in 1970, but in 1972 under the authority of the Federal Insecticide, Fungicide and Rodenticide Act ( FIFRA), the EPA permitted their use in three cases: subsurface ground insertion for termite control, dipping of non food plant roots and tops, and mothproofing of woolen textiles and carpets under conditions of no effluent discharge ( ATSDR, 2000; USEPA, 1980). The latter two registered uses were abandoned by the manufacturer in 1974, as was the ground insertion termiticide use in 1987; therefore, all uses of aldrin and dieldrin have been canceled ( ATSDR, 2000; USEPA, 1980).

In the United States, the use of aldrin peaked at 19,000,000 lbs in 1966 and had declined to about 10,500,000 lbs by 1970; concurrently, dieldrin use declined from 1,000,000 lbs to about 650,000 lbs ( USEPA, 1980). There was some importation of these compounds during the 1970s and early mid 1980s; the USEPA has reported that no aldrin has been imported since 1985 ( ATSDR, 2000). Aldrin was not imported into the United States prior to the 1974 cancellation decision; however, Shell International ( Holland) imported the chemical for limited use from 1974 to 1985 ( with the exception of 1979 and 1980, when imports were temporarily suspended). An estimated 1 to 1.5 million lbs of aldrin were imported annually from 1981 to 1985, after which time importation ceased. By 1987, all uses of aldrin had been cancelled voluntarily by the manufacturer ( ATSDR, 2000). In 1972, USEPA cancelled all but the following three uses of dieldrin: subsurface ground insertion for termite control, the dipping of non food plant roots and tops, and mothproofing in manufacturing processes using completely closed systems. This cancellation decision was finalized in 1974. By 1987, all uses of dieldrin had been cancelled voluntarily by its manufacturer ( the Shell Chemical Company) ( ATSDR, 2000). 3 2 Aldrin/ Dieldrin   February 2003 3.2 Environmental Release and Fate Aldrin is listed as a Toxic Release Inventory ( TRI) chemical. In 1986, the Emergency Planning and Community Right to Know Act ( EPCRA) established the Toxic Release Inventory ( TRI) of hazardous chemicals. Created under the Superfund Amendments and Reauthorization Act ( SARA) of 1986, EPCRA is also sometimes known as SARA Title III. The EPCRA mandates that larger facilities publicly report when TRI chemicals are released into the environment. This public reporting is required for facilities with more than 10 full time employees that annually manufacture or produce more than 25,000 pounds, or use more than 10,000 pounds, of a TRI chemical ( USEPA, 1996/ 1999; USEPA, 2000a).

Under these conditions, facilities are required to report the pounds per year of aldrin released into the environment both on and off site. The production, import, and use of aldrin had been cancelled by the time the TRI was instated; therefore, no release or transfer data were reported. In 1995, Resource Conservation and Recovery Act ( RCRA) Subtitle C hazardous waste treatment and disposal facilities were added to the list of those facilities required to present release data to the TRI. This addition became effective for the 1998 reporting year, which is the most recent TRI data currently available. Waste treatment facilities from three states ( AR, MI, TX) reported releases of aldrin in 1998, with on and off site releases totaling 25,622 pounds. The on site quantity is subdivided into air emissions, surface water discharges, underground injections, and releases to land. Most of the aldrin released to the environment was released directly to land ( 22,000 lbs) ( USEPA, 2000b).

Although the TRI data can be useful in giving a general idea of release trends, it is far from exhaustive and has significant limitations. For example, only industries that meet TRI criteria ( at least 10 full time employees and the manufacture and processing of quantities exceeding 25,000 lbs/ year, or use of more than 10,000 lbs/ year) are required to report releases. These reporting criteria do not account for releases from smaller industries. Also, the TRI data is meant to reflect releases and should not be used to estimate general exposure to a chemical ( USEPA, 2000c).

Aldrin is included in the Agency for Toxic Substances and Disease Registry's ( ATSDR) Hazardous Substance Release and Health Effects Database ( HazDat). This database records detections of listed chemicals in site samples; aldrin was detected in 40 states ( states without detections are AZ, DE, HI, ME, MS, MT, NV, NM, OR, WY) ( ATSDR, 2000). The National Priorities List ( NPL) of hazardous waste sites, created in 1980 by the Comprehensive Environmental Response, Compensation & Liability Act ( CERCLA), is a listing of some of the most health threatening waste sites in the United States. Aldrin was detected in NPL hazardous waste sites in 31 states ( USEPA, 1999).

Dieldrin is also included in the ATSDR's HazDat. Dieldrin was detected in 40 states ( states without detections are AZ, DE, HI, MN, MT, NV, NM, OR, UT, WY) ( ATSDR, 2000). Dieldrin was detected in NPL hazardous waste sites in 38 states ( USEPA, 1999). 3 3 Aldrin/ Dieldrin   February 2003 In summary, aldrin and dieldrin have not been produced in the United States since 1974, and all uses of the pesticide were cancelled by 1987. Aldrin had been used mostly on corn and citrus products. Dieldrin had been used mostly on corn, potatoes, tomatoes, and citrus products. Aldrin was imported to the United States from Holland from 1974 to 1985 ( with the exception of 1979 and 1980) in quantities of approximately 1 to 1.5 million lbs/ year. TRI data from 1998 suggest that aldrin continues to be released into the environment, even though the chemical is no longer produced or used in the United States. Aldrin's presence and persistence in the environment is evidenced by detections of the compound in hazardous waste sites in at least 31 states ( at NPL sites), as well as detections in site samples in at least 40 states ( listed in ATSDR's HazDat).

Most aldrin introduced into the environment is relatively rapidly converted through epoxidation to dieldrin, which in turn is notably persistent in the environment due to its very low solubility in water and its extremely low volatility. Because dieldrin is also extremely apolar, it displays a high affinity for fat and is thus retained in animal fats, plant waxes, and other similar organic matter in the environment. This fat solubility can lead to a progressive accumulation of dieldrin in the food chain, which theoretically could eventually produce concentrations in organisms that might exceed lethal limits to predators or consumers ( Sittig, 1991; USEPA, 1980).

Environmental Media Transport and Distribution Given the historical uses of aldrin and dieldrin, their point of entry into the environment has most typically been the soil ( IPCS, 1989b). Because of their strong adsorption to soils and their low aqueous solubilities, significant downward leaching of these compounds through the soil profile would not be anticipated ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b). As discussed further below, most aldrin in the soil is gradually converted to dieldrin under most environmental conditions ( ATSDR, 2000; HSDB, 2000a; IPCS, 1989b). Field studies of the application of aldrin to the surface layer of various types of soils have demonstrated nearly quantitative adsorption by organic matter and clay minerals, and that even 5 years after application, residual aldrin and dieldrin were still found in the surface layer with very little penetration to lower soil depths ( IPCS, 1989b). Water has been found to compete with aldrin for adsorption sites in clay minerals, and thus aldrin binds to a greater extent when the soil is dry; in dry soils, mineral components play the largest role in adsorption, whereas in moist soils, organic materials are predominant; and other factors being equal, adsorption is expected to be the lowest in sandy soils having minimal organic content ( IPCS, 1989b).

In one summarized study, aldrin was applied to the upper 5 inches of a silt loam soil ( HSDB, 2000a). Combining the results for non disked soil with those of soil disked for one summer only, the reported distribution of residual aldrin after 10 years by soil depth was as follows: 11 to 13% ( 0 to 2 inches), 29 to 33% ( 2 to 4 inches), 29 to 33% ( 4 to 6 inches), 23 to 29% ( 6 to 9 inches). In a study by Weisgerber et al. ( 1974), aldrin was quantified at different soil depths 3 to 6 months after its application at about 3 kg/ ha to soils used for growing corn in several countries. Their findings are summarized below in Table 3 1. As is readily apparent, 3 4 Aldrin/ Dieldrin   February 2003 aldrin demonstrated little proclivity to migrate down through the various soil profiles; similar results were observed for soils in England and Germany used to grow wheat ( Weisgerber et al.,

Table 3 1. Aldrin Mobility in Soils Used to Grow Corn1 Soil Depth ( cm) Residual Aldrin Levels in Soils Used to Grow Corn2: ppm (% Total Extractable)

Germany England Spain United States 0! 10 0.78 ( 78%) 1.30 (~ 100%) 0.83 ( 96.5%) 0.50 ( 98%)

10! 20 0.18 ( 18%) < 0.01 (< 1%) 0.02 ( 2.3%) 0.01 ( 1.96%)

20! 40 0.03 ( 3%) < 0.01 (< 1%) 0.01 ( 1.2%) < 0.01 (< 1%)

40! 60 < 0.01 (< 1%) < 0.01 (< 1%) < 0.01 (< 1%) < 0.01 (< 1%)

1 From Weisgerber et al. ( 1974). 2 Measured 5, 6, 4, or 3 months ( respectively by country) after the application of about 3 kg aldrin/ ha.

1974), and for various laboratory studies of soil samples in columns that were eluted with water ( HSDB, 2000a; IPCS, 1989b).

In a laboratory test of six types of soil placed in chromatographic columns, the percentage of applied dieldrin that eluted with 1600 ml of water varied from 1% in loam soil, to 65% in soil containing 93% sand ( IPCS, 1989b). Little dieldrin leaching was observed in a similar column experiment involving 3 soil types eluted with about 30 L of water over 120 hours ( IPCS, 1989b), and even with high temperatures and prolonged leaching, dieldrin has been considered essentially immobile ( HSDB, 2000b). Experimentally determined log soil sorption coefficients ( K oc) of 2.61 to 4.45 for aldrin and 3.87 for dieldrin further suggest that these compounds are not highly mobile in soils and will not appreciably leach to groundwater ( HSDB, 2000a, b). In areas with poorly controlled erosion, surface run off can carry particle associated aldrin and dieldrin into surface waters; in the absence of sediment, however, rain water run off does not appear to be a major transport mechanism ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b). The equilibrium ratio of dieldrin concentration in soil to that in water was shown to be 100 to 500 for mineral soils and likely to be 5 to 6 times higher for aldrin ( IPCS, 1989b). Vapor diffusion is, generally, regarded as the principal mechanism whereby aldrin and dieldrin ascend the soil profile. The role of upward mass flow in capillary water through a moisture gradient, though demonstrated in laboratory studies, is now thought to be relatively insignificant in the field ( IPCS, 1989b).

Most studies have concluded that the observed, relatively rapid loss of aldrin and dieldrin from soil during the first few months after application is principally attributable to volatilization processes ( ATSDR, 2000; IPCS, 1989b). There is substantial evidence for this. Mosquitoes were shown to be killed by vapors emanating from treated soils and it is known that when aldrin 3 5 Aldrin/ Dieldrin   February 2003 is incorporated into soil, it is most readily lost from the surface layer ( IPCS, 1989b). Various laboratory studies have reportedly ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b) demonstrated that: volatilization of aldrin is significantly faster than that of dieldrin ( about 20 fold, in one case); chamber rates of volatilization for each chemical decrease with time ( about 50% over 6 to 7 hours in one experiment with dieldrin); volatilization of aldrin from sands increases ( from trace levels to up to 7.33% after 6 hours) with increased water content in the sands and/ or increased humidity in the air passing over the sands; and volatilization rates of aldrin from sand, loam, and humus during the first or second hour after application were 1.08, 0.21, and 0.08, or 0.59, 0.18, and 0.09% per ml evaporated water, respectively.

Actual field studies on volatilization losses from soil are limited in number and appear available only for dieldrin ( ATSDR, 2000; IPCS, 1989b). Reported volatilization losses include 2.8% after 18 weeks and 4.5% after 1 year. In one study involving a very high application rate ( 22 kg/ ha or 10 ppm) to soils under three different soil moisture conditions, volatilization losses after 5 months were 18% in a plot kept moist by irrigation, 7% in a non irrigated plot receiving only natural rainfall, and only 2% in a plot flooded to a depth of 10 cm.

Related studies examining the overall loss ( by any mechanism) of aldrin or dieldrin from soil have been reviewed ( ATSDR, 2000; HSDB, 2000a; IPCS, 1989b; Verscheuren, 1983). After several years of field application of aldrin at three different rates, residues were shown to be higher in clay loam than in sandy loam soils ( half lives of 79 to 97 vs. 36 to 45 days, respectively), although the rate of conversion to dieldrin was higher in the latter ( ATSDR, 1993; HSDB, 2000a). An early study examined various Illinois soils that had been treated with aldrin, demonstrating that aldrin was indeed transformed to dieldrin, and concluding that loss of related residues was a two stage process   a comparatively rapid phase during the first year after application in which, typically, ~ 75% of the applied dose was lost. An extended second phase displayed residue half lives of 2 to 4 years, perhaps due to increased content of the more stable dieldrin in the total residue ( IPCS, 1989b). This same qualitative result was observed when aldrin was applied to muck and loam soils, with respective half lives of 3.75 and 2.40 months during the first half year and then 13.0 and 9.7 months for the following 3 years ( HSDB, 2000b).

Following the application of 1.5 kg aldrin/ ha to flooded soil, approximately 56, 45, 26, 12, and 0% remained after 30, 90, 120, 240, and 270 days, respectively ( HSDB, 2000b). Similarly, 3.5 years after the application of 20 or 200 lbs of aldrin/" 6 inch" acre to a Miami silt loam, only 1.12 and 2.55% remained, respectively ( HSDB, 2000b). Other reported studies have demonstrated an increase in aldrin loss from soils with increasing temperature, more rapid loss under upland ( 80% water saturated) than under flooded conditions, and more rapid loss from the upper layers of most soils ( HSDB, 2000b). Although some contrary findings have been reported, aldrin losses from temperate soils often appear more rapid than from tropical soils ( IPCS, 1989b). Separate studies carried out with dieldrin suggest residue rate losses that are considerably slower than those observed for aldrin, but the reported range is wide ( IPCS, 1989b); one study reported an average time of 8 years for the disappearance of 95% of the dieldrin residues; however, much slower, as well as intermediate, rates can also be found in the literature. Verschueren ( 1983) indicates a period of 1 to 6 years for the disappearance of 75 to 100% of 3 6 Aldrin/ Dieldrin   February 2003 aldrin from soils; for dieldrin, comparable indicated values were 3 to 25 years for 75 to 100%, and 12.8 years for 95%.

As noted previously, aldrin and dieldrin are highly resistant to being leached from soils, and as a consequence, they have only rarely been observed in ground water samples ( ATSDR, 2000; IPCS, 1989b). By contrast, surface waters have frequently been reported to contain small amounts of these pesticides ( more frequently dieldrin), probably as a result of surface run off of rain water in which most of the residues are adsorbed to sediments ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b). The ultimate fate of these small residue amounts is not known with certainty, but adsorption to sediments, volatilization, and bioconcentration have been postulated to play the most significant roles, with certain degradation mechanisms ( especially abiotic) also involved to some extent ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b).

While volatilization is considered an important pathway for water residues of these compounds, conflicting data are reported in the literature ( e. g., volatilization half life for dieldrin of hours to months) ( HSDB, 2000b). Rates are expected to vary directly with wind and water current velocities, and inversely with the depth of the water body ( HSDB, 2000a). Half lives for the volatilization of aldrin from pure water and from three natural waters were reported to be 0.38 and 0.59 to 0.60 hours, respectively. From a different study, volatilization rates from water during the first and second hours were reported to be 16.3 and 6.03% per ml evaporated water, respectively ( HSDB, 2000a). Verschueren ( 1983) and HSDB ( 2000a) indicate a derived half life value of 185 hours ( 7.7 days) for aldrin in a 1m column of water at 25 ° C. Using a water solubility of 0.20 mg/ L and a vapor pressure of 6 × 10! 6 mm Hg ( both measured at 25 ° C), an estimated Henry's Law constant of 1.27 × 10! 5, and reasonable assumptions for wind velocity, current velocity and water depth, half lives for aldrin in streams, rivers, and lakes were calculated as 105.5 hours, 133.9 hours, and 6873.1 hours ( 286.4 days), respectively ( HSDB, 2000a). For dieldrin, Verschueren ( 1983) and IPCS ( 1989b) indicate a derived half life value of 12,940 hours ( 539.2 days) in a 1 m column of water at 25 ° C. A cited experimental volatilization rate for dieldrin in water is 5% of the reaeration rate, which, using typical reaeration rates for ponds, rivers, and lakes, yields estimated evaporation half lives for dieldrin of 72, 14, and 52 days, respectively; however, values as short as 6 to 9 hours under certain laboratory conditions have been reported ( HSDB, 2000b).

From the previous discussion, it is apparent that a substantial portion of the aldrin and dieldrin used in agriculture is, generally, considered to reach the atmosphere ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b). Although there are data to suggest that dieldrin may be transported great distances in the atmosphere, in general, only small amounts have been detected by global atmospheric sampling ( ATSDR, 2000; IPCS, 1989b). Washout by rain may play an important role in preventing atmospheric accumulation of these compounds, but the significance of this mechanism is called into question by observations of no detectable levels of aldrin or dieldrin in soils adjacent to treated areas ( IPCS, 1989b). As further discussed below, various atmospheric degradation mechanisms may also play a key role in minimizing accumulation. 3 7 Aldrin/ Dieldrin   February 2003 Environmental Degradation The principal transformation of aldrin that occurs in all aerobic and biologically active soils is its epoxidation to dieldrin ( ATSDR, 2000; HSDB, 2000a; IPCS, 1989b). This reaction has also been observed in plants, but does not occur under anaerobic conditions ( IPCS, 1989b). Soil transformation to aldrin dicarboxylic acid has also been well established ( ATSDR, 2000; IPCS, 1989b). Fungi and other soil microbes have been demonstrated to degrade aldrin in culture ( ATSDR, 2000; HSDB, 2000a; IPCS, 1989b). Dieldrin is much more resistant to biodegradation than aldrin, and thus microbial degradation is likely only a minor pathway for the loss of dieldrin from soils ( ATSDR, 2000; HSDB, 2000b; IPCS, 1989b). This is reflected in the long times ( years) that have been reported for dieldrin half lives or times required for 50 to 100% loss ( see previous discussion). There is some evidence that certain microbes can metabolize dieldrin to photodieldrin and that this is more likely to occur under anaerobic conditions. A number of studies have detected low to very low soil concentrations of photodieldrin ( ATSDR, 2000; HSDB, 2000b; IPCS, 1989b). Although not biodegraded in standard screening tests, a number of soil microorganisms have been isolated that are capable of degrading dieldrin to limited degrees ( ATSDR, 2000; HSDB, 2000b; IPCS, 1989b).

Under aqueous conditions, biodegradation of aldrin is expected to be slow; none was observed through the third subculture with one mixed culture inoculum from sewage, while an activated sludge biodegraded 1.5% of an initial amount of aldrin over an unspecified amount of time ( HSDB, 2000a). A water surface film collected off the coast of Hawaii degraded 8.1% of added aldrin to its diol after 30 days; a pure culture of a marine alga degraded 23.3% of the initial aldrin to dieldrin and 5.2% to the diol; and a pure culture of Aerobacter aerogenes was reported to degrade 36 to 46% of an initial amount of aldrin within 24 hours ( HSDB, 2000a). Under anaerobic aqueous conditions, aldrin is not epoxidized to dieldrin, but has been reported to be completely degraded to other compounds within 60 days by an anaerobic sewage sludge ( ATSDR, 2000; IPCS, 1989b). Although no biodegradation of dieldrin was reported in some studies of river waters, microorganisms isolated from certain lake water and lake bottom sediments may be able to transform some dieldrin to photodieldrin under anaerobic conditions ( ATSDR, 2000).

However, dieldrin was not significantly degraded under anaerobic conditions by an active waste water sludge or by sewage sludge microorganisms in 2 studies and was only degraded by 11% after 48 hours or by 24% after 32 days in 2 other studies ( ATSDR, 2000). By comparison, an aerobic activated sludge was able to degrade 55% of the initial level of dieldrin in 9 days, another activated sludge achieved dieldrin degradation of 30 to 60% ( time frame not specified in review), and a mixed anaerobic microbial culture degraded 10 : g dieldrin/ ml by 50% in 30 days ( ATSDR, 2000). Some biodegradation pathways of aldrin and dieldrin are illustrated below in Figure 3 1, taken from Verschueren ( 1983). Although intended to describe metabolism under oceanic conditions, they are relevant to other soil and fresh water environments as previously discussed.

Various abiotic processes may also contribute to the environmental degradation of aldrin and dieldrin, although their role seems generally to be considered relatively limited ( ATSDR, 3 8 Aldrin/ Dieldrin   February 2003 2000; HSDB, 2000a, b; IPCS, 1989b). The high reactivity of hydroxyl and other atmospheric free radicals could possibly play a role in the degradation of aldrin and dieldrin occurring as vapors ( IPCS, 1989b) and the half life for vapor phase aldrin reacting with photochemically generated hydroxyl radicals has been estimated at 35 minutes ( HSDB, 2000a). As might be expected from its weak absorption to wavelengths above 290 nm, sunlamp photolysis of aldrin vapor has been observed to be rather slow   60% in 1 week, vs. 16% in a dark control ( HSDB, 2000a). Both aldrin and dieldrin are susceptible to photochemical reactions following irradiation by sunlight or Figure 3 1. Biodegradation Pathways for Aldrin and Dieldrin, With Particular Reference to Oceanic Conditions ( Verschueren, 1983)

UV under abiotic laboratory conditions, with epoxidation and isomerization transformations resulting in the formation of photoaldrin and photodieldrin ( ATSDR, 2000; HSDB, 2000b; IPCS, 1989b). These reactions are illustrated below in Figure 3 2, taken from Verschueren ( 1983). Photodieldrin is believed to be a stable photoproduct of aldrin as it no longer contains a chromophore. It has, in fact, proven resistant to further photolysis ( ATSDR, 2000).

Other experimental work found that while photoaldrin was produced upon sunlight or ultraviolet light ( UV) irradiation of aldrin, the major photoproduct was an unbridged compound that had lost a chlorine atom from the 3 position; the yield of photoaldrin ( and photodieldrin from dieldrin) was also found to be substantially enhanced in the presence of benzophenone or other ketones ( IPCS, 1989b). Photoproducts arising from the loss of chlorine atoms have also been observed upon the irradiation of photoaldrin and photodieldrin in the presence of triethylamine ( ATSDR, 2000). Based on reactions with hydroxyl radicals, the atmospheric half life of dieldrin has been estimated at approximately 1 day, but could be longer if it is associated with particulate matter ( ATSDR, 2000). Again, it should be noted that while small amounts of dieldrin have 3 9 Aldrin/ Dieldrin   February 2003 been found in some atmospheric samples, neither aldrin, photoaldrin, nor photodieldrin has been detected ( ATSDR, 2000; IPCS, 1989b). Therefore, if the latter two photoproducts occur to any significant extent in the atmosphere, they do not appear stable enough to accumulate.

When irradiated with UV or natural sunlight in an oxygenated aqueous solution, aldrin underwent little degradation unless amino and humic acids commonly found in natural waters were also present ( ATSDR, 2000; IPCS, 1989b). Photolysis half lives of 4.7 to 11 days for thin Figure 3 2. Photochemical Transformations ( Principally Atmospheric) Reported for Aldrin and Dieldrin ( Verschueren, 1983)

films of aldrin irradiated at > 300 nm have been reported and exposure of an aldrin film to sunlight for 1 month resulted in a solution containing 2.6% aldrin, 9.6% photoaldrin, 4.1% dieldrin, 24.1% photodieldrin, and 59.7% of an unidentified photoproduct ( HSDB, 2000a). The persistence of aldrin in river water was studied in sealed glass jars that were maintained under sunlight and artificial fluorescent light conditions; amounts remaining after 1 hour, 1 week, 2 weeks, 4 weeks, and 8 weeks were 100, 100, 80, 40, and 20%, respectively ( Verschueren, 1983; HSDB, 2000a). The conversion was principally to dieldrin ( Verschueren, 1983). Irradiation at 238 nm for 48 hours converted 75% of the aldrin in filtered natural field water to dieldrin ( ATSDR, 2000).

Hydrolysis is not a significant abiotic degradation mechanism for aqueous dieldrin, as it occurs with a half life of > 4 years; however, aqueous dieldrin will reportedly degrade to photodieldrin in the presence of sunlight with an approximate half life of 2 to 4 months with the process being accelerated in waters containing photosensitizers ( HSDB, 2000b). In somewhat contrary findings, when the persistence of dieldrin was studied in sealed glass jars of river water that were maintained under sunlight and artificial fluorescent light conditions, 100% of the initial dieldrin was reported to be still present after 8 weeks ( Verschueren, 1983). 3 10 Aldrin/ Dieldrin   February 2003 While it is possible that some aldrin and dieldrin may undergo photochemical degradation ( as a result of UV irradiation in surface layers), only small amounts of photodieldrin have been observed in soil samples, and the extent to which these may have resulted from microbial action is not certain ( ATSDR, 2000; IPCS, 1989b). It appears that photochemical reactions may be responsible for the epoxidation of some aldrin to dieldrin, and some dieldrin to photodieldrin, that has been observed on the leaf surfaces of various plants ( IPCS, 1989b).

With respect to other abiotic mechanisms, dieldrin has been reported to be susceptible to ozone mediated degradation, and the clay diluents used in dust formulations of aldrin and dieldrin ( especially acidic kaolinite and attapulgite) have been reported to contribute to their decomposition ( IPCS, 1989b).

Bioaccumulation As suggested by their relatively high K ow s, both aldrin and dieldrin have moderate to high potentials for bioaccumulation ( ATSDR, 2000; HSDB, 2000a, b; IPCS, 1989b). Aldrin and dieldrin uptake by plants has been reported to be substantially higher in root crops than in grain crops; root crops ( e. g., carrots, radishes, and turnips) are much more likely to take up residues from treated soils, whereas it is rare in grain crops for residues to reach detectable levels in the grain ( IPCS, 1989b). In one model ecosystem study, corn was planted in vermiculite soil to which 2.09 ppm radiolabeled aldrin had been applied; after 14 days, the corn contained 2.83 ppm radiolabeled residue, of which 0.762 ppm was aldrin and 1.538 ppm dieldrin ( ATSDR, 2000). About 78% of the residues were found in the roots, with the remainder in the shoots. The mechanism of uptake into plants for these compounds is not clear. It may vary considerably with species and the nature of the soils in which they are grown, and apparently involves both absorption through roots and absorption of vapors through leaves ( ATSDR, 2000; IPCS, 1989b). A vole was introduced into this same model ecosystem on day 15, and after 5 days was found to have aldrin and dieldrin concentrations of 0.08 and 3.56 ppm, respectively ( ATSDR, 2000).

The bioaccumulation and biomagnification of aldrin occur mostly through its conversion products ( IPCS, 1989b). Biotransfer factors ( BTFs) for beef and milk, defined as the ratio of a compound in beef or milk ( mg/ kg) to its daily intake by the animal ( mg/ day), have been estimated for aldrin to be 0.085 and 0.023, respectively ( ATSDR, 2000). In vegetables, a bioconcentration factor ( BCF, the ratio of a compound's concentration in above ground plant parts to that in soil) of 0.021 has been calculated for aldrin ( ATSDR, 2000). Similarly, BTFs for beef and milk and a vegetable BCF have been estimated for dieldrin, these being 0.008, 0.011, and 0.098, respectively ( ATSDR, 2000). BCFs for these compounds in various aquatic organisms ( fish, molluscs, algae, waterflea, etc.) have been reported to be in the range of 100 to 15,000, while in various amphibian, avian, earthworm, and mammalian species values have been of the order of 2 to 400 BCFs ( HSDB, 2000a, b; IPCS, 1989b; Verschueren, 1983).

Environmental Fate Summary In summary, aldrin that is applied to soil can be expected to largely be converted to dieldrin through both biological and abiotic mechanisms. Dieldrin is much more persistent and 3 11 Aldrin/ Dieldrin   February 2003 both compounds will strongly adsorb to sediment or dust particles. Potential for leaching into ground water is low, but soil run off of rain water may carry particle adsorbed residues into surface waters. Substantial volatilization of both compounds to the atmosphere is thought to occur, where significant levels of photochemical epoxidation, isomerization, and reaction with free radicals ( hydroxyl radical) may take place. Washout of atomospheric aldrin and dieldrin may also be significant. Monitoring data suggest that dieldrin is widely dispersed in the atmosphere. However, while the ultimate fate of it and its related photoproducts remains unclear, it appears they do not accumulate in the atmosphere. Biodegradation of aldrin is generally slow and along with hydrolysis, is thought to be an unimportant fate process for dieldrin. Bioconcentration and bioaccumulation of these compounds and their residues are significant and, in addition to their being continuing contaminants of soil, water, and air, they are often found in aquatic organisms, wildlife, foods, and humans ( HSDB, 2000a, b; IPCS, 1989b; USEPA, 1980). 3 12 Aldrin/ Dieldrin   February 2003 References ATSDR. 2000. Agency for Toxic Substances and Disease Registry. Toxicological profile for aldrin/ dieldrin ( Update). Draft for public comment. Atlanta, GA: U. S. Dept. of Health and Human Services, Public Health Service, ATSDR.

ATSDR. 1993. Agency for Toxic Substances and Disease Registry. Toxicological profile for aldrin/ dieldrin: Update. Atlanta, GA: U. S. Dept. of Health and Human Services, Public Health Service, ATSDR.

HSDB. 2000a. Hazardous Substances Data Bank. Aldrin. Retrieved Sep. 20, 2000. Bethesda, MD: National Library of Medicine, Specialized Information Services Division, Toxicology and Environmental Health Information Program, TOXNET.

HSDB. 2000b. Hazardous Substances Data Bank. Dieldrin. Retrieved Sep. 20, 2000. Bethesda, MD: National Library of Medicine, Specialized Information Services Division, Toxicology and Environmental Health Information Program, TOXNET.

IPCS. 1989a. International Programme on Chemical Safety. Aldrin and dieldrin health and safety guide. Health and safety guide no. 21. Geneva, Switzerland: World Health Organization, IPCS.

IPCS. 1989b. International Programme on Chemical Safety. Aldrin and dieldrin. Environmental health criteria 91. Geneva, Switzerland: World Health Organization, IPCS.

Sittig, M. 1991. Handbook of toxic and hazardous chemicals and carcinogens, 3rd ed., vol. 1. Park Ridge, NJ: Noyes Publications, pp. 6 64, 598 601.

USEPA. 2000a. What is the Toxic Release Inventory? Available on the Internet at: http:// www. epa. gov/ tri/ general. htm Last modified February 28, 2000.

USEPA. 2000b. TRI Explorer: Geographic Report. Available on the Internet at: http:// www. epa. gov/ triexplorer/ geography. htm. Last modified May 5, 2000.

USEPA. 2000c. The Toxic Release Inventory ( TRI) and Factors to Consider when Using TRI Data. Available on the Internet at: http:// www. epa. gov/ tri/ tri98/ 98over. pdf. Last modified August 11, 2000. Link to site at: http:// www. epa. gov/ tri/ tri98.

USEPA. 1999. Superfund Hazardous Waste Site Basic Query Form. Available on the Internet at: http:// www. epa. gov/ superfund/ sites/ query/ basic. htm. Last modified December 1,1999.

USEPA. 1996/ 1999. U. S. Environmental Protection Agency. Proposed Cancer Guidelines. Available on the Internet at http:// www. epa. gov/ ORD/ WebPubs/ carcinogen / carcin. pdf. USEPA. 1992. U. S. Environmental Protection Agency. Aldrin drinking water health advisory. Washington, DC: USEPA Office of Water. 3 13 Aldrin/ Dieldrin   February 2003 USEPA. 1988. U. S. Environmental Protection Agency. Dieldrin health advisory. Washington, DC: USEPA Office of Water.

USEPA. 1980. U. S. Environmental Protection Agency. Ambient water quality criteria for aldrin/ dieldrin. Document no. EPA 440/ 5 80 019. Washington, DC: USEPA Office of Water, Office of Water Regulations and Standards, Criteria and Standards Division.

Verschueren, K. 1983. Handbook of environmental data on organic chemicals, 2nd ed. New York, NY: Van Nostrand Reinhold, pp. 168 173, 513 518.

Weisgerber, I., J. Kohli, R. Kaul, W. Klein, and F. Korte. 1974. Fate of aldrin 14C in maize, wheat and soils under outdoor conditions. J. Agric. Food Chem. 22( 4): 609 612 ( as cited in HSDB, 2000a; IPCS, 1989b). 4 1 Aldrin/ Dieldrin   February 2003 4.0 EXPOSURE FROM DRINKING WATER 4.1 Aldrin 4.1.1 Ambient Occurrence To understand the presence of a chemical in the environment, an examination of ambient occurrence is useful. In a drinking water context, ambient water is source water existing in surface waters and aquifers before treatment. The most comprehensive and nationally representative data describing ambient water quality in the United States are being produced through the United States Geological Survey's ( USGS) National Water Quality Assessment ( NAWQA) program. ( NAWQA, however, is a relatively young program and complete national data are not yet available from their entire array of sites across the nation.)

Data Sources and Methods The USGS instituted the NAWQA program in 1991 to examine water quality status and trends in the United States. NAWQA is designed and implemented in such a manner as to allow consistency and comparison between representative study basins located around the country, facilitating interpretation of natural and anthropogenic factors affecting water quality ( Leahy and Thompson, 1994).

The NAWQA program consists of 59 significant watersheds and aquifers referred to as " study units." The study units represent approximately two thirds of the overall water usage in the United States and a similar proportion of the population served by public water systems. Approximately one half of the nation's land area is represented ( Leahy and Thompson, 1994).

To facilitate management and make the program cost effective, approximately one third of the study units at a time engage in intensive assessment for a period of 3 to 5 years. This is followed by a period of less intensive research and monitoring that lasts between 5 and 7 years. This way all 59 study units rotate through intensive assessment over a 10 year period ( Leahy and Thompson, 1994). The first round of intensive monitoring ( 1991 to 1996) targeted 20 watersheds. This first group was more heavily slanted toward agricultural basins. A national synthesis of results from these study units focusing on pesticides and nutrients has been compiled and analyzed ( Kolpin et al., 1998; Larson et al., 1999; USGS, 1999a).

Aldrin was not an analyte for either the ground water or the surface water NAWQA studies included in the pesticide and nutrient national synthesis ( Kolpin et al., 1998; Larson et al., 1999; USGS, 1999b). Because of analytical and budget constraints the NAWQA program targets certain pesticides, many of which have high use and/ or have potential environmental significance ( Larson et al., 1999; USGS, 1999a). Aldrin may have been excluded because it has not been used in agriculture since the early 1970s and all of its uses were discontinued in the mid 1980s ( USGS, 1999a). Also, aldrin breaks down in the environment to dieldrin ( among other degradates), a compound that was analyzed in the NAWQA studies ( USGS, 1999b). Finally, aldrin persisting in the environment is more likely to be found in sediments or biotic tissues 4 2 Aldrin/ Dieldrin   February 2003 because of its strong hydrophobicity and sorption potential ( ATSDR, 1993; Nowell, 1999; USGS, 2000). Consequently, NAWQA investigators focused their aldrin occurrence studies on bed sediments and aquatic biota tissue ( Nowell, 1999).

Aldrin is an organochlorine insecticide. As a group, organochlorines are hydrophobic and resist degradation. Hydrophobic (" water hating") compounds have low water solubilities and strong tendencies to sorb to organic material in sediments and accumulate in the tissue of aquatic biota, where they can persist for long periods of time ( ATSDR, 1993; USGS, 2000). Organochlorines may be present in bed sediments and tissues of aquatic systems even when they are undetectable in the water column using conventional methods ( Nowell, 1999).

To determine their presence in hydrologic systems of the United States, the NAWQA program has investigated organochlorine pesticide detections in bed sediments and biotic tissue, focusing on the organochlorine insecticides that were used heavily in the past ( Nowell, 1999). The occurrence of aldrin, one of the top three insecticides used for agriculture in the 1960s and widely used to kill termites in structures until the mid 1980s, was investigated in this study ( Nowell, 1999; USGS, 1999a). Sampling was conducted at 591 sites from 1992 to 1995 in the 20 NAWQA study units where the first round of intensive assessment took place. Two of these basins, the Central Nebraska Basins and the White River Basin in Indiana, are located in the corn belt where aldrin use was heavy during the 1960s. Details regarding sampling techniques and analytical methods are described by Nowell ( 1999).

Results Aldrin was not detected in aquatic biota tissue samples. However, it was detected in stream bed sediment samples. The occurrence frequencies above the Method Detection Limit ( MDL) of 1 µ g/ kg and basic summary statistics indicate that occurrence in sediments is very low ( Table 4 1). Both the median and 95th percentile concentrations were reported as non detections (< MDL) across all land use categories.

Aldrin was detected in stream bed sediments only at agricultural or mixed land use sites, perhaps reflecting the heavy agricultural use in the late 1960s and early 1970s. Interesting, in light of the more recent termiticide use, no urban detections were reported. This may be partly a function of the NAWQA sampling design that targeted basins more representative of agricultural and mixed land use conditions for the first round of intensive monitoring from which these sediment data were produced ( see Section <IP_ADDRESS>). Data from later rounds are not yet available. The occurrence of a toxic compound in stream sediments is pertinent to drinking water concerns because some desorption of the compound from sediments into water will occur through equilibrium reactions, although in very low concentrations. The occurrence of aldrin in sediments is also quite low ( see Table 4 1). 4 3 Aldrin/ Dieldrin   February 2003 Table 4 1. Aldrin Detections in Stream Bed Sediments1 Detection Frequency (% Samples > MDL of 1 µ g/ kg) Concentration Percentiles ( All Samples; µ g/ kg Dry Weight)

Median 95th Maximum urban 0.0% nd2 nd nd mixed 0.5% nd nd 3 agricultural 0.6% nd nd 2.2 forest rangeland 0.0% nd nd nd all sites 0.4% nd nd 3 1 Nowell, 1999.

2 Not detected in concentration greater than MDL.

4.1.2 Drinking Water Occurrence The Safe Drinking Water Act ( SDWA), as amended in 1986, required Public Water Systems ( PWSs) to monitor for specified " unregulated" contaminants, on a 5 year cycle, and to report the monitoring results to the states. Unregulated contaminants do not have an established or proposed National Primary Drinking Water Regulation ( NPDWR); however, they are contaminants that were formally listed and required for monitoring under federal regulations. The intent was to gather scientific information on the occurrence of these contaminants to enable a decision as to whether or not regulations were needed. All non purchased community water systems ( CWSs) and non purchased non transient non community water systems ( NTNCWSs), with greater than 150 service connections, were required to conduct this unregulated contaminant monitoring. Smaller systems were not required to conduct this monitoring under federal regulations, but were required to be available to monitor if the state decided such monitoring was necessary. Many states collected data from smaller systems. Additional contaminants were added to the Unregulated Contaminant Monitoring ( UCM) program in 1991 ( USEPA, 1991) for required monitoring that began in 1993 ( USEPA, 1992).

Aldrin has been monitored under the SDWA Unregulated Contaminant Monitoring ( UCM) program since 1993 ( USEPA, 1992). Monitoring ceased for small public water systems ( PWSs) under a direct final rule published January 8, 1999 ( USEPA, 1999a), and ended for large PWSs with promulgation of the new Unregulated Contaminant Monitoring Regulation ( UCMR) issued September 17, 1999 ( USEPA, 1999b) and effective January 1, 2001. At the time the UCMR lists were developed, the Agency concluded there were adequate monitoring data for a preliminary regulatory determination. This obviated the need for continued monitoring under the new UCMR list. 4 4 Aldrin/ Dieldrin   February 2003 Data Sources, Data Quality, and Analytical Methods Currently, there is no complete national record of unregulated or regulated contaminants in drinking water from PWSs collected under SDWA. Many states have submitted unregulated contaminant PWS monitoring data to EPA databases, but there are issues of data quality, completeness, and representativeness. Nonetheless, a significant amount of state data are available for UCM contaminants that can provide estimates of national occurrence.

The National Contaminant Occurrence Database ( NCOD) is an interface to the actual occurrence data stored in the Safe Drinking Water Information System ( Federal version; SDWIS/ FED) and can be queried to provide a summary of the data in SDWIS/ FED for a particular contaminant. The drinking water occurrence data for aldrin presented here were derived from monitoring data available in the SDWIS/ FED database.

The data in this report have been reviewed, edited, and filtered to meet various data quality objectives for the purposes of this analysis. Hence, not all data from a particular source were used, only data meeting the quality objectives described below were included. The sources of these data, their quality and national aggregation, and the analytical methods used to estimate a given contaminant's national occurrence ( from these data) are discussed in this section ( for further details see USEPA, 2001a, b).

UCM Rounds 1 and 2 The 1987 UCM contaminants include 34 volatile organic compounds ( VOCs) ( USEPA, 1987). Aldrin, a synthetic organic compound ( SOC), was not among these contaminants. The UCM ( 1987) contaminants were first monitored coincident with the Phase I regulated contaminants, during the 1988 to 1992 period. This period is often referred to as " Round 1" monitoring. The monitoring data collected by the PWSs were reported to the states ( as primacy agents), but there was no protocol in place to report these data to EPA. These data from Round 1 were collected by EPA from many states over time and put into a database called the Unregulated Contaminant Information System, or URCIS.

The 1993 UCM contaminants include 13 SOCs and 1 inorganic contaminant ( IOC) ( USEPA, 1991). Monitoring for the UCM ( 1993) contaminants began coincident with the Phase II/ V regulated contaminants in 1993 through 1998. This is often referred to as " Round 2" monitoring. The UCM ( 1987) contaminants were also included in the Round 2 monitoring. As with other monitoring data, PWSs reported these results to the states. EPA, during the past several years, has requested that all states submit these historic data to EPA and they are now stored in the SDWIS/ FED database.

Monitoring and data collection for aldrin, a UCM ( 1993) contaminant, began in Round 2. Therefore, the following discussion regarding data quality screening, data management, and analytical methods focuses on SDWIS/ FED. Discussion of the URCIS database is included where relevant, but it is worth noting that the various quality screening, data management, and 4 5 Aldrin/ Dieldrin   February 2003 analytical processes were nearly identical for the two databases. For further details on the two monitoring periods as well as the databases see USEPA ( 2001a, b).

Developing a Nationally Representative Perspective The Round 2 data contain contaminant occurrence data from a total of 35 primacy entities ( including 34 states and data for some tribal systems). However, data from some states are incomplete and biased. Furthermore, the national representativeness of the data is problematic because the data were not collected in a systematic or random statistical framework. These state data could be heavily skewed to low occurrence or high occurrence settings. Hence, the state data were evaluated based on pollution potential indicators and the spatial/ hydrologic diversity of the nation. This evaluation enabled the construction of a cross section from the available state data sets that provides a reasonable representation of national occurrence.

A national cross section from these state Round 2 contaminant databases was established using the approach developed for the EPA report A Review of Contaminant Occurrence in Public Water Systems ( USEPA, 1999c). This approach was developed to support occurrence analyses for EPA's Chemical Monitoring Reform ( CMR) evaluation. It was supported by peer reviewers and stakeholders. The approach cannot provide a " statistically representative" sample because the original monitoring data were not collected or reported in an appropriate fashion. However, the resultant " national cross section" of states should provide a clear indication of the central tendency of the national data. The remainder of this section provides a summary description of how the national cross section for the SDWIS/ FED ( Round 2) database was developed. The details of the approach are presented in other documents ( USEPA, 2001a; USEPA, 2001b); readers are referred to these for more specific information.

Cross Section Development As a first step in developing the cross section, the state data contained in the SDWIS/ FED database ( that contains the Round 2 monitoring results) were evaluated for completeness and quality. Some state data in SDWIS/ FED were unusable for a variety of reasons. Some states reported only detections, or their data had incorrect units. Datasets only including detections are obviously biased. Other problems included substantially incomplete data sets without all PWSs reporting ( USEPA, 2001a Sections II and III).

The balance of the states remaining after the data quality screening were then examined to establish a national cross section. This step was based on evaluating the states' pollution potential and geographic coverage in relation to all states. Pollution potential is considered to ensure a selection of states that represent the range of likely contaminant occurrence and a balance with regard to likely high and low occurrence. Geographic consideration is included so that the wide range of climatic and hydrogeologic conditions across the United States are represented, again balancing the varied conditions that affect transport and fate of contaminants, as well as conditions that affect naturally occurring contaminants ( USEPA, 2001b Sections III. A. and III. B.). 4 6 Aldrin/ Dieldrin   February 2003 The cross section states were selected to represent a variety of pollution potential conditions. Two primary pollution potential indicators were used. The first factor selected indicates pollution potential from manufacturing/ population density and serves as an indicator of the potential for VOC contamination within a state. Agriculture was selected as the second pollution potential indicator because the majority of SOCs of concern are pesticides ( USEPA, 2001b Section III. A.). The 50 individual states were ranked from highest to lowest based on the pollution potential indicator data. For example, the state with the highest ranking for pollution potential from manufacturing received a ranking of 1 for this factor and the state with the lowest value was ranked as number 50. States were ranked for their agricultural chemical use status in a similar fashion.

The states' pollution potential rankings for each factor were subdivided into four quartiles ( from highest to lowest pollution potential). The cross section states were chosen from all quartiles for both pollution potential factors to ensure representation, for example, from the following: states with high agrichemical pollution potential rankings and high manufacturing pollution potential rankings; states with high agrichemical pollution potential rankings and low manufacturing pollution potential rankings; states with low agrichemical pollution potential rankings and high manufacturing pollution potential rankings; and states with low agrichemical pollution potential rankings and low manufacturing pollution potential rankings ( USEPA, 2001b Section III. B.). In addition, some secondary pollution potential indicators were considered to further ensure that the cross section states included the spectrum of pollution potential conditions ( high to low). The cross section was then reviewed for geographic coverage throughout all sectors of the United States.

The data quality screening, pollution potential rankings, and geographic coverage analysis established a national cross section of 20 Round 2 ( SDWIS/ FED) states. The cross section states provide a good representation of the nation's varied climatic and hydrogeologic regimes and the breadth of pollution potential for the contaminant groups ( Figure 4 1).

Cross Section Evaluation To evaluate and validate the method for creating the national cross sections, the method was used to create smaller state subsets from the 24 state, Round 1 ( URCIS) cross section and aggregations. Again, states were chosen to achieve a balance from the quartiles describing pollution potential, and a balanced geographic distribution, to incrementally build subset crosssections of various sizes. For example, the Round 1 cross section was tested with subsets of 4, 8 ( the first 4 state subset plus 4 more states), and 13 ( 8 state subset plus 5) states. Two additional cross sections were included in the analysis for comparison: a cross section composed of 16 biased states eliminated from the 24 state cross section for data quality reasons and a crosssection composed of all 40 Round 1 states ( USEPA, 2001b Section III. B. 1). 4 7 Aldrin/ Dieldrin   February 2003 Figure 4 1. Geographic Distribution of Cross Section States for Round 2 ( SDWIS/ FED)

Round 2 ( SDWIS/ FED)

Alaska Arkansas Colorado Kentucky Maine Maryland Massachusetts Michigan Minnesota Missouri New Hampshire New Mexico North Carolina North Dakota Ohio Oklahoma Oregon Rhode Island Texas Washington These Round 1 incremental cross sections were then used to evaluate occurrence for an array of both high and low occurrence contaminants. The comparative results illustrate several points. The results are quite stable and consistent for the 8, 13, and 24 state cross sections. They are much less for the 4 state, 16 state ( biased), and 40 state ( all Round 1 states) cross sections. The 4 state cross section is apparently too small to provide balance both geographically and with pollution potential, a finding that concurs with past work ( USEPA, 1999c). The CMR analysis suggested that a minimum of six to seven states was needed to provide balance both geographically and with pollution potential. The CMR report used eight states out of the available data for its nationally representative cross section ( USEPA, 1999c). The 16 state and 40 state cross sections, both including biased states, provided occurrence results that were unstable and inconsistent for a variety of reasons associated with their data quality problems ( USEPA, 2001b Section III. B. 1).

The 8, 13, and 24 state cross sections provide very comparable results, are consistent, and are usable as national cross sections to provide estimates of contaminant occurrence. Including greater data from more states improves the national representation and the confidence in the results, as long as the states are balanced related to pollution potential and spatial coverage. The 20 state cross section provides the best, nationally representative cross section for the Round 2 data.