The LED 10 for HCBD was calculated by fitting the quantal polynomial model7 to the tumor dose response data reported by Kociba et al. ( 1977). Since the mortality rate was significantly increased in the male rats exposed at the high dose ( which is the only dose with an increased tumor incidence in animals), the tumor data from the female rats were used. In accordance with current guidance ( U. S. EPA, 1992d, 1999), the human equivalent dose was calculated by assuming dose equivalency based on body weight raised to the 3/ 4 power. The best fit to the data is shown in Figure 8 2. The ED 10 was found to be 4.9 mg/ kg day, and the LED 10 was 2.5 mg/ kg day. Linear extrapolation from the LED 10 to the origin yields a slope of 4 × 10 2 ( mg/ kg day) 1. HCBD   February 2003 8 9 0.00 0.05 0.10 0.15 0.20 0.25 0.30 0 1 2 3 4 5 6 7 Human Equivalent Dose ( mg/ kg day) Extra Risk ED10 Best Fit Line Data Points Lower confidence limit on ED10 ( LED10) Figure 8 2. Renal Tumor Dose Response Curves.

Non linear Approach The non linear approach is used when available data indicate that the dose response curve for tumor induction is not linear, and that cancer may not be the result of a direct DNA damage mechanism. As discussed previously, data from the study by Kociba et al. ( 1977) indicate that the dose response curve is strongly non linear, and that renal tumors only occur at HCBD doses that cause frank renal toxicity and increased mortality. Therefore, tumor data from this study are not considered suitable for dose response extrapolation, and the non linear approach should be evaluated.

For HCBD, mode of action considerations suggest carcinogenicity may be secondary to renal toxicity, which has a threshold ( see Section 7.4.3, Mode of Action), and the RfD approach was used for non linear analysis in accordance with the proposed cancer guidelines ( U. S. EPA, 1999). The point of departure ( Pdp) selected for use was the BMDL for renal tubular histological lesions in female mice. This is because a Pdp based on a sensitive key precursor of the neoplastic response is more protective and more reliable than a Pdp based on the neoplastic response itself ( U. S. EPA, HCBD   February 2003 8 10 1999). The BMDL for renal toxicity calculated from the NTP ( 1991) study was 0.1 mg/ kg day in female mice. Application of a composite uncertainty factor of 300 ( 10 for extrapolation from animals to humans; 10 for human variability; and 3 for database deficiencies) yields a dose of 3 × 10 4 mg/ kg day, which is the RfD for HCBD. This RfD is also protective of potential carcinogenic effects under the non linear approach.

By the non linear approach, a health reference level ( HRL) of 2 : g/ L can also be derived using the Reference Dose ( RfD) for HCBD of 3 × 10 4 mg/ kg day. The RfD is an estimate of the daily oral dose to the human population that is likely to be without appreciable risk of adverse effects over a lifetime exposure. This dose was converted to a drinking water equivalent concentration of 10 : g/ L by multiplying the RfD by the default body weight for an adult ( 70 kg) and dividing the result by the default daily intake of drinking water for an adult ( 2 L/ day). For derivation of the HRL, it was assumed that about 20% of an individual's total exposure to HCBD was attributable to drinking water. Multiplication of the drinking water equivalent concentration by 0.2 yields the HRL of 2 : g/ L ( rounded to 1 significant number). The HRL was derived as follows:

HRL = RfD × BW × RSC DI Where:

RfD = Reference dose for HCBD in drinking water, 3 × 10 4 mg/ kgday BW = Body weight of an adult, 70 kg DI = Daily intake of water for an adult, 2 L/ day RSC = Relative Source Contribution, default value of 20%

Therefore:

HRL = ( 3 × 10 4 mg/ kg day) × ( 70 kg) × 0.20 2 L/ day = 2 : g/ L ( rounded to 1 significant number).

However, the HRL of 0.9 : g/ L derived from linear approach is used as the preliminary health effect level in this document. ( See Section 8.2.5). The linear approach is used as the default because of potential genotoxicity of HCBD metabolites.

8.2.3 Extrapolation Model and Rationale In Section 8.2.2., the carcinogenicity of HCBD was evaluated using both linear and nonlinear approaches. Because of the lack of data, it is not certain which method of cancer risk evaluation is most appropriate for HCBD. On the one hand, some tests indicate that one or more of the metabolites of HCBD are mutagenic, suggesting direct damage to renal mitochondrial DNA by its reactive metabolites. On the other hand, direct observations on cancer dose response clearly HCBD   February 2003 8 11 support a nonlinear curve, with no observable increase in tumors at doses that do not induce significant renal necrosis and regeneration. This is supported by the observation that tumors occur only in the kidney and not in other tissues that are not significantly injured by HCBD. Therefore, the tumor data from the Kociba et al. ( 1977) study are not considered suitable for linear dose response extrapolation.

Although HCBD metabolites have some indication of mutagenic activity, they are not likely to play a significant role in tumor causation due to their weak activity. Moreover, mutations of mitochondrial DNA may result in mitochondrial dysfunction ( See Section 7.4.3), which would support cytotoxicity and nonlinear approach. There should also be decreased concern over genotoxicity for humans because the activity of HCBD metabolizing enzymes, particularly renal $ lyase, may be many fold lower in humans than the corresponding enzymes in rats ( see section 6.3). In addition, human exposure levels ( see Section 9.3) are about 4 orders of magnitude lower than the human equivalent dose corresponding to the dose at which tumor incidence was reported in Kociba et al. ( 1977) study. In consideration of the overall evidence, the non linear approach may be appropriate for HCBD. The draft Ambient Water Quality Criteria Document for Hexachlorobutadiene ( U. S. EPA, 1998a) has recommended using the nonlinear approach for carcinogenicity assessment of HCBD.

According to the 1999 U. S. EPA Draft Guidelines for Carcinogen Risk Assessment, " When the mode of action information indicates that the dose response may be adequately described by both a linear and a nonlinear approach, then the default is to present both the linear and margin of exposure analyses." As this can be done without contradicting previous guidelines, both linear and nonlinear analyses are presented.

8.2.4 Cancer Potency and Unit Risk Table 8 5 summarizes the cancer values derived for HCBD. Analysis of tumor dose response information from the Kociba et al. ( 1977) study using the linear extrapolation approach from the proposed carcinogen risk assessment guidelines ( U. S. EPA, 1999) resulted in a slope factor of 4 × 10 2 ( mg/ kg day) 1. This value is about half of the slope factor of 7.8 × 10 2 ( mg/ kg day) 1 derived previously using the linearized multistage ( LMS) model ( U. S. EPA, 1997a), but most of the apparent difference may be attributable to the different methods used to calculate human equivalent doses from the animal doses ( the scaling factor used in the LMS approach assumed body weight to the 2/ 3 power, while a factor of body weight raised to the 3/ 4 was used for the Pdp method). Based on the slope factor of 4 × 10 2 ( mg/ kg day) 1 derived using the LED 10 approach with linear extrapolation, the unit risk is 1.1 × 10 6 per (: g/ L) and the drinking water concentration that corresponds to a lifetime excess risk of 1 × 10 6 is 0.9 : g/ L. HCBD   February 2003 8 12 Table 8 5. Summary of Cancer Risk Values for HCBD.

Approach Parameter Value LMSa ( U. S. EPA, 1991) Slope 7.8 × 10 2 ( mg/ kg day) 1 Unit Risk 2.2 × 10 6 per (: g/ L)

Water Concentration at risk of 1 × 10 6 0.5 : g/ L LED 10, linear extrapolation LED 10 ( tumors) b 2.5 mg/ kg day Slope 4 × 10 2 ( mg/ kg day) 1 Unit Risk 1.1 × 10 6 per (: g/ L)

Water Concentration at risk of 1 × 10 6 ( HRL) 0.9 : g/ L Nonlinear Pdp ( BMDL) 0.1 mg/ kg day Uncertainty factor 300 HRL 2 : g/ L a Animal to human dose extrapolation based on body weight2/ 3 b Animal to human dose extrapolation based on body weight3/ 4 8.2.5 Discussion of Confidence The available database associating HCBD and carcinogenicity is limited. There are no human data. The evidence is obtained only in one chronic dietary study in a single species ( Sprague Dawley rats) ( Kociba et al., 1977), where rats developed severe renal toxicity preceding tumor formation. The tumors were seen only at a high dose which exceeded the maximum tolerated dose ( MTD, i. e., greater than 10% body weight depression) in both sexes of rats and produced high mortality in the males. Similar renal toxicity observed in a 30 day study of HCBD in rats by the same laboratory and in another 90 day subchronic study in mice ( NTP, 1991) strengthens the idea that the tumor formation is induced by cytotoxicity. Both the NTP ( 1991) and Kociba et al. ( 1977) studies tested a sufficient number of animals.

A limitation of the Kociba et al. ( 1977) study is the selection and spacing of doses. Although the study employed an adequate number of animals, the doses selected for testing were separated by a factor of 10 ( 0, 0.2, 2, and 20 mg/ kg day). Thus, there are no observations between the dose of 2 mg/ kg day ( causing no tumors), and the dose of 20 mg/ kg day ( causing a 15% tumor response in females and a 23% tumor response in males). More doses between 2 and 20 mg/ kg day would better delineate the shape of the dose response curve. HCBD   February 2003 8 13 A weight of evidence analysis of the available data as a whole indicates that the confidence in using either the linear or nonlinear approach is not high; this is particularly true for the linear method which is based on only one data point at a high dose exceeding the MTD. However, the possible genotoxicity of HCBD metabolites forces the use of the linear approach as default. Thus, the HRL of 0.9 µ g/ L derived from the linear approach is used as the preliminary health effect level in this document. HCBD   February 2003 9 1 9.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK FROM DRINKING WATER 9.1 Regulatory Determination for Chemicals on the CCL The Safe Drinking Water Act ( SDWA), as amended in 1996, required the Environmental Protection Agency ( EPA) to establish a list of contaminants to aid the Agency in regulatory priority setting for the drinking water program. EPA published a draft of the first Contaminant Candidate List ( CCL) on October 6, 1997 ( 62 FR 52193, U. S. EPA, 1997b). After review of and response to comments, the final CCL was published on March 2, 1998 ( 63FR 10273, U. S. EPA 1998d). The CCL grouped contaminants into three major categories as follows:

Regulatory Determination Priorities  Chemicals or microbes with adequate data to support a regulatory determination,

Research Priorities  Chemicals or microbes requiring research for health effects, analytical methods, and/ or treatment technologies,

Occurrence Priorities  Chemicals or microbes requiring additional data on occurrence in drinking water.

The March 2, 1998 CCL included one microbe and 19 chemicals in the regulatory determination priority category. More detailed assessments of the completeness of the health, treatment, occurrence and analytical method data led to a subsequent reduction of the regulatory determination priority chemicals to a list of 12 ( one microbe and 11 chemicals) which was distributed to stakeholders in November 1999.

SDWA requires EPA to make regulatory determinations for no fewer than five contaminants in the regulatory determination priority category by August 2001. In cases where the Agency determines that a regulation is necessary, the regulation should be proposed by August 2003 and promulgated by February 2005. The Agency is given the freedom to also determine that there is no need for a regulation if a chemical on the CCL fails to meet one of three statutory criteria established by SDWA and described in Section 9.1.1.

9.1.1 Criteria for Regulatory Determination These are the three criteria used to determine whether or not to regulate a chemical on the CCL:

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, HCBD   February 2003 9 2 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 findings for all criteria are used in making a determination to regulate a contaminant. As required by SDWA, a decision to regulate commits the EPA to publication of a Maximum Contaminant Level Goal ( MCLG) and promulgation of a National Primary Drinking Water Regulation ( NPDWR) for that contaminant. The agency may determine that there is no need for a regulation when a contaminant fails to meet one of the criteria. A decision not to regulate a contaminant is considered a final Agency action and is subject to judicial review. The Agency can choose to publish a Health Advisory ( a nonregulatory action) or other guidance for any contaminant on the CCL independent of the regulatory determination.

9.1.2 National Drinking Water Advisory Council Recommendations In March 2000, the EPA convened a Working Group under the National Drinking Water Advisory Council ( NDWAC) to help develop an approach for making regulatory determinations. The Working Group developed a protocol for analyzing and presenting the available scientific data, and recommended methods to identify and document the rationale supporting a regulatory determination decision. The NDWAC Working Group report was presented to and accepted by the entire NDWAC in July 2000.

Because of the intrinsic difference between microbial and chemical contaminants, the Working Group developed separate but similar protocols for microorganisms and chemicals. The approach for chemicals was based on an assessment of the impact of acute, chronic, and lifetime exposures, as well as a risk assessment that includes evaluation of occurrence, fate, and doseresponse The NDWAC protocol for chemicals is a semi quantitative tool for addressing each of the three CCL criteria. The NDWAC requested that the Agency use good judgement in balancing the many factors that need to be considered in making a regulatory determination.

The EPA modified the semi quantitative NDWAC suggestions for evaluating chemicals against the regulatory determination criteria and applied them in decision making. The quantitative and qualitative factors for hexachlorobutadiene ( HCBD) that were considered for each of the three criteria are presented in the sections that follow.

9.2 Health Effects The first criterion asks if the contaminant may have an adverse effect on the health of persons. Because all chemicals have adverse effects at some level of exposure, the challenge is to define the dose at which adverse health effects are likely to occur, and estimate a dose at which adverse health effects are either not likely to occur ( threshold toxicant), or have a low probability for occurrence ( non threshold toxicant). The key elements that must be considered in evaluating the first criterion are the mode of action, the critical effect( s), the dose response for critical effect( s), the RfD for threshold effects, and the slope factor for non threshold effects. HCBD   February 2003 9 3 A description of the health effects associated with exposure to HCBD is presented in Chapter 7 of this document and summarized below in Section 9.2.2. Chapter 8 and Section 9.2.3 present dose response information, where applicable, for threshold and non threshold health effects.

9.2.1 Health Criterion Conclusion The available toxicological data indicate that HCBD has the potential to cause adverse health effects in animals, and probably in humans. The available human data involve inhalation exposure and are confounded by simultaneous exposures to other chemicals in an occupational setting; thus, attributing observed effects to specific levels of HCBD exposure is not possible. In rodents, there is clear evidence of renal damage resulting from acute, subchronic, and chronic HCBD oral exposures. A few animal studies have also reported liver effects and neurotoxicity. Review of animal dose response data endpoints indicates that subchronic and chronic LOAEL values for HCBD toxicity are generally at 2 mg/ kg day and above. The RfD for HCBD is 3 × 10 4 mg/ kg day ( Chapter 8). Limited evidence of carcinogenic potential in rodents suggests that HCBD may be carcinogenic secondary to renal tubular epithelial cell cytotoxicity. However, data in humans are lacking. Both linear and non linear approaches were evaluated for cancer dose response assessment. Using the non linear approach, the RfD protects both non cancer and cancer effects. However, in the presence of data supporting the potential genotoxicity of HCBD metabolites, the linear approach is used as default, with a 10 6 risk at a drinking water concentration of 0.9 µ g/ L.

9.2.2 Hazard Characterization and Mode of Action Implications Data for the human health effects of HCBD are limited to a few studies of occupational exposure to HCBD. A relationship could not be established from these studies between HCBD exposure and toxic effects either because of concurrent exposure to other chemicals or because of equivocal results.

Studies in animals show the selective effect of HCBD on the kidney, specifically the proximal tubule. Renal toxicity in rodents has been shown with single acute exposures to 100   200 mg HCBD/ kg, and with short term exposures to 3 mg/ kg day and above. Subchronic and chronic studies in rodents show clear dose related renal damage at 2 mg/ kg day and above. Progressive events over time include changes in kidney weight, increased urinary excretion of coproporphyrin, and increased renal tubular epithelial hyperplasia.

Other noncancer effects associated with HCBD exposure in animals include developmental effects and neurotoxicity ( Harleman and Seinen, 1979; Badaeva, 1983; Badaeva et al., 1985). However, these effects were observed at higher doses than for renal toxicity. Pups with lower birth weights and reduced growth were reported at maternal dose of 8.1 15 mg/ kg day in rats ( Badaeva, 1983; Harleman and Seinen, 1979).

Results from mutagenicity studies with HCBD are ambiguous. In the presence of appropriate metabolic activation conditions, HCBD and its metabolites are mutagenic in some ( Vamvakas et al., 1988; Reichert et al., 1984), but not all studies. HCBD metabolites have been shown to bind to mitochondrial DNA in vivo in mice ( Schrenk and Dekant, 1989), and induce DNA repair in cultured HCBD   February 2003 9 4 porcine kidney cells ( Vamvakas et al., 1989), suggesting its genotoxic potential. No human studies of HCBD carcinogenicity have been reported and only one lifetime animal study has been performed ( Kociba et al., 1977). In this study, neoplastic changes occurred only at the highest dose which exceeded the maximum tolerated dose ( MTD), i. e. there was increased mortality, greater than 10% decrease in body weight and severe renal toxicity. Because these significant adverse effects were observed at the high dose, tumor formation may be secondary to cytotoxicity.

The nephrotoxicity of HCBD is dependent on a multistep bioactivation mechanism involving both kidney and liver enzymes. The ultimate step in this pathway is a $ lyase mediated degradation of a HCBD metabolite that generates a highly reactive thioketene in proximal tubule cells.. In vitro studies suggest that cortical mitochondria are the critical subcellular target for toxicity of the bioactivated sulfur conjugates of HCBD. Covalent binding of this reactive HCBD metabolite to cellular macromolecules ( e. g. proteins, mitochondrial DNA), and the resultant mitochondrial dysfunction is believed to contribute to the renal cytotoxicity and tumors observed in animals. Recent evidence suggests that HCBD induced " 2: globulin accumulation contributes to renal injury in male rats. However, renal tubular necrosis and renal tubular tumors were observed in both male and female rats following HCBD exposure ( Kociba et al., 1977), and renal necrosis and regeneration were also observed in male and female mice ( NTP, 1991). Therefore, " 2: globulin accumulation cannot be the sole mechanism for HCBD induced carcinogenesis.

One important issue in the evaluation of the hazard posed by HCBD is the applicability of rodent mechanistic data to humans. In vitro studies with human renal cytosol and cultured human proximal tubule cells suggest that humans have the potential to form the HCBD glutathione conjugates and to metabolize HCBD cysteine conjugates to toxic metabolites. However, the rate of metabolism, particularly for the reaction catalyzed by $ lyase, appears to be much lower for humans than rodents ( Lock, 1994; Lash et al., 1990).

It has been generally observed that existing nephropathy or age related kidney degeneration can increase the risk of renal injury or exacerbate nephrotoxicity in humans. Therefore, sensitive populations for HCBD exposure may include people with pre existing kidney or liver damage or the elderly. Although it is unlikely that human newborns would be acutely exposed to significant doses of HCBD, acute exposures for young rats and mice cause toxicity at lower doses than for adults ( Hook et al., 1983; Lock et al., 1984).

9.2.3 Dose Response Characterization and Implications in Risk Assessment Dose response information from several key studies of HCBD toxicity in animals is summarized in Table 9 1. These studies currently provide the most reliable information on threshold levels for HCBD toxicity in animals exposed via the oral route.

Noncancer effects In short term studies, a LOAEL of 10 mg/ kg day and a NOAEL of 3 mg/ kg day were identified for reduced body weight gain and food consumption in female Sprague Dawley rats administered HCBD in their diets for 30 day. Renal tubular degeneration, necrosis and regeneration HCBD   February 2003 9 5 Table 9 1. Dose Response Information from Several Key Studies of HCBD Toxicity ( Oral Exposure).

Study Species No./ Sex Doses mg/ kg day Duration NOAEL mg/ kgday LOAEL mg/ kgday Effects Short term Studies Kociba et al. ( 1977) Rat Sprague Dawley 4 F 1.310e+ 10 30 days 3 10 Reduced body weight gain, food consumption; increased hemoglobin concentration, relative kidney weight; renal tubular degeneration, necrosis, regeneration.

Jonker et al. ( 1993b) Rat Wistar 5 M 5 F 2.25828 4 weeks 2.25 8 Decreased liver weight, plasma creatinine, body weight, adrenal weight; renal tubular cytomegaly.

Harleman and Seinen ( 1979) Rat Wistar 6 M 6 F 0 4.6 14.0 35.3 14 days  4.6 Decreased body weight gain and food conversion efficiency; renal tubular epithelial cell degeneration.

Stott et al. ( 1981) Rat Sprague Dawley 5 M 0.22 3 weeks 0.2 20 Decreased body weight gain; increased relative kidney weight; kidney damage.

NTP ( 1991) Mouse B6C3F 1 5 M 5 F 0 M 0 F 3 M 5 F 12 M 16 F 40 M 49 F 2 weeks  3 M 5 F Renal tubular necrosis. Table 9 1 ( continued)

Study Species No./ Sex Doses mg/ kg day Duration NOAEL mg/ kgday LOAEL mg/ kgday Effects HCBD   February 2003 9 6 Subchronic Studies NTP ( 1991) Mouse B6C3F 1 10 M 10 F 0 M 0 F 0.1 M 0.2 F 0.4 M 0.5 F 1.5 M 1.8 F 4.9 M 4.5 F 16.8 M 19.2 F 13 weeks 1.5 M 0.2 F 4.9 M 0.5 F Renal tubular cell regeneration ( increased epithelial nuclei and basophilic staining)

Chronic Studies Kociba et al. ( 1977) Rat Sprague Dawley 39   40 M, F 0.222 22   24 months 0.2 2 Increased kidney weight; renal tubular epithelial hyperplasia and neoplasia.

M = male; F = female were observed at 30 mg/ kg day ( Kociba et al., 1971; Schwetz et al., 1977). A LOAEL of 8 mg/ kgday and a NOAEL of 2.25 mg/ kg day were identified for decreased body weight gain and renal tubular effects in Wistar rats given HCBD in their diets for 4 weeks ( Jonker et al., 1993b). A 3 week oral exposure with male Sprague Dawley rats identified a LOAEL of 20 mg/ kg day and a NOAEL of 0.2 mg/ kg day for kidney damage and increased relative kidney weight ( Stott et al., 1981), and a 2 week feeding study in Wistar rats identified a LOAEL of 4.6 mg/ kg day ( the lowest dose tested) for renal tubular epithelial cell degeneration ( Harleman and Seinen, 1979). A 2 week oral exposure study in B6C3F 1 mice reported a LOAEL of 3   5 mg/ kg day ( the lowest dose tested) for renal tubular necrosis ( NTP, 1991). Thus, renal effects in rodents resulting from short term exposure to HCBD appear to have LOAELs of around 5   20 mg/ kg day, depending on the species and strain used, the length of exposure, and the method of administration.

In a subchronic oral exposure study of HCBD in B6C3F 1 mice, a NOAEL of 1.5 mg/ kg day was identified for male mice based on renal tubular cell regeneration ( NTP, 1991). Tubular regeneration occurred in 1 of 10 females in the lowest dose group ( 0.2 mg/ kg day). The study authors concluded that a NOAEL for female mice could not be identified from these data ( NTP, 1991). However, EPA ( U. S. EPA, 1998a) and others ( WHO, 1994) have concluded that the effect observed at 0.2 mg/ kg day is not statistically significant, and therefore consider this dose to be the NOAEL for female mice. Because tubular regeneration occurred in 1 of 10 females at 0.2 mg/ kg day, this NOAEL may be close to a minimal LOAEL for renal injury.

Only one study of lifetime oral exposure to HCBD was located ( Kociba et al., 1977). This study identified a NOAEL of 0.2 mg/ kg day and a LOAEL of 2 mg/ kg day in rats, based on an HCBD   February 2003 9 7 increase in renal tubular epithelial cell hyperplasia/ regeneration. The value of this NOAEL from a chronic study is the same as the equivocal NOAEL of 0.2 mg/ kg day identified in the 13 week NTP study in female mice ( NTP, 1991), indicating the female mice may be more sensitive than rats to HCBD.

The Reference Dose ( RfD) for HCBD is 3 × 10 4 mg/ kg day ( Chapter 8). The RfD is " an estimate ( with uncertainty spanning approximately an order of magnitude) of a daily exposure to the human population ( including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects over a lifetime" ( U. S. EPA, 1993). The RfD is derived from a BMDL of 0.1 mg/ kg day for renal tubular epithelial cell hyperplasia/ regeneration from the NTP ( 1991) studies. A composite uncertainty factor of 300 was used in the derivation of the RfD to account for: extrapolation from animals to humans ( factor of 10); protection of sensitive subpopulations ( factor of 10); and database deficiency ( factor of 3) because of lack of a 2 generation reproductive study.

Cancer effects The single lifetime exposure study in rats is also a source of data on tumor formation ( Kociba et al., 1977). Only at the highest dose, 20 mg/ kg day, were tumors seen in both sexes. This dose exceeded the level at which significant noncancer effects were seen, such as mortality, renal toxicity, and body weight depression. In this study, the second highest dose was 2 mg/ kg day and there were no tumors in this exposed group. While slope of the dose response curve cannot be determined from the data set, it must be kept in mind that the purpose of the Kociba et al.( 1977) bioassay was for hazard identification, not quantitative risk analysis.

Under EPA's 1986 Guidelines for Carcinogen Risk Assessment ( U. S. EPA, 1986), HCBD is classified as Group C, possible human carcinogen. Using the linearized multistage model, a slope factor of 7.8 × 10 2 per mg/ kg day was calculated at the 95th upper confidence level ( U. S. EPA, 1991c). Under EPA's 1999 draft Guidelines for Carcinogen Risk Assessment ( USEPA, 1999), HCBD is classified as 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 are inadequate data to perform an assessment. Both the linear and nonlinear doseresponse extrapolation approaches were used to quantify cancer risk ( U. S. EPA, 1998a) because both cytotoxicity and mutagenic mode of action may be involved. The linear approach yields a slope of 4 × 10 2 per mg/ kg day. Using the non linear approach, the RfD was used, yielding the resulting dose of 3 × 10 4 mg/ kg day. EPA's draft Ambient Water Quality Criteria for hexachlorobutadiene ( U. S. EPA, 1998a) recommended using the non linear approach for dose response extrapolation. As discussed previously, data from Kociba et al. ( 1977) indicated that the tumor dose response curve is strongly non linear, and that renal tumors only occur at HCBD doses that cause frank toxicity. However, the presence of data supporting the genotoxicity of HCBD metabolites forces the conservative choice of a linear approach to be more appropriate for HCBD.

The conclusion from the dose response analysis is that HCBD is a weak carcinogen because it is carcinogenic only at cytotoxic dose. HCBD   February 2003 9 8 9.3 Occurrence in Public Water Systems The second criterion asks if the contaminant is known to occur or if 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 order to address this question, the following information was considered:

° Monitoring data from public water systems ° Ambient water concentrations and releases to the environment ° Environmental fate Data on the occurrence of HCBD in public drinking water systems were the most important determinants in evaluating the second criterion. EPA looked at the total number of systems that reported detections of HCBD, as well as those that reported concentrations of HCBD above an estimated drinking water health reference level ( HRL) ( U. S. EPA, 2001c). For noncarcinogens, the estimated HRL level was calculated from the RfD assuming that 20% of the total exposure would come from drinking water. For carcinogens, the HRL was the 10 6 risk level. The HRLs are benchmark values that were used in evaluating the occurrence data while the risk assessments for the contaminants were being developed.

The available monitoring data, including indications of whether or not the contamination is a national or a regional problem, are included in Chapter 4 of this document and summarized below. Additional information on production, use, and fate are found in Chapters 2 and 3.

9.3.1 Occurrence Criterion Conclusion HCBD has never been specifically manufactured as a commercial product in the United States, but is generated as waste by product from the chlorination of hydrocarbons. The available data for HCBD use indicate an overall downward trend. The ten year pattern of TRI releases to surface water is variable but generally decreasing within the range from 5 to 1,911 pounds. The physicochemical properties of HCBD and the available data for environmental fate indicate that HCBD in surface water is likely to be rapidly degraded by biotic and abiotic processes although it has the potential for bioaccumulation. Monitoring data indicate that HCBD is infrequently detected in public water supplies. When HCBD is detected, it very rarely exceeds the HRL or a value of onehalf of the HRL. Chemical treatment of drinking water and leaching from drinking water surfaces are not expected to contribute to significantly elevated levels of HCBD in drinking water.

9.3.2 Monitoring Data Drinking Water HCBD has been detected in a small percentage of public water supply ( PWS) samples collected under the authority of the Safe Drinking Water Act. Occurrence data for HCBD in drinking water are presented and analyzed in Chapter 4 of this document. Data from two monitoring periods HCBD   February 2003 9 9 were available for analysis. Data from Round 1 were collected during the period 1987 to 1992. Data from Round 2 were collected during the period 1993 to 1997. Round 1 and 2 monitoring detected HCBD in only 0.13% and 0.05% of all samples analyzed, respectively. When data are expressed on a PWS basis, Round 1 and Round 2 monitoring detected HCBD at least once in 0.35% ( 228 systems) and 0.18% ( 117 systems) of the tested water supplies, respectively.

The median and 99th percentile concentrations for all samples ( i. e., samples with and without detectable levels of HCBD) were below the minimum reporting level ( MRL). When subsets of the data containing only samples with detectable levels of HCBD were analyzed, the median and 99th percentile concentrations for Round 1 were 0.25 : g/ L and 10 : g/ L, respectively. The median and 99th percentile for Round 2 detections were 0.30 : g/ L and 1.5 : g/ L, respectively.

When monitoring results were compared to a value of one half of the HRL, 0.163% of Round 1 ( 106 systems) and 0.079% of Round 2 ( 51 systems) water supplies exceeded this benchmark at least once during the reporting period. The percentages of water supplies that exceeded the HRL at least once in Round 1 and Round 2 monitoring were 0.114% ( 74 systems) and 0.018% ( 11 systems), respectively.

PWSs with detected levels of HCBD were widely distributed throughout the United States ( see Figures 4 2 and 4 3 in this document), and no clear patterns of regional geographic occurrence were evident.

Ambient Water HCBD has not been detected in the ground water samples reviewed and/ or analyzed under the U. S. Geological Survey National Ambient Water Quality Assessment ( NAWQA) program. The first round of intensive monitoring in the ongoing NAWQA was conducted from 1991 to 1996 and targeted 20 watersheds. Data from each NAWQA study unit were augmented by additional data from local, state, and federal agencies that met specified criteria.( See Section 4.1.1). HCBD was not detected in rural and urban wells of the local, State, and federal data set compiled by NAWQA. These data represent untreated ground water of the conterminous United States for the years 1985 1995.

A review of highway and urban runoff studies also found no detections of HCBD.

9.3.3 Use and Fate Data Significant quantities of HCBD are generated in the United States as waste by product from the chlorination of hydrocarbons, although HCBD has never been specifically manufactured as a commercial product domestically. No recent estimate could be found on the by product amounts, but in 1982, it was estimated that about 28 million pounds were generated ( ATSDR, 1994). HCBD imports dropped during the late 1970s, the period for which data are reported ( Howard, 1989). HCBD   February 2003 9 10 In all environmental media, HCBD binds strongly to particles ( ATSDR, 1994). It is readily adsorbed to airborne particulate matter, to sediments in water, and to soil organic particles. Volatilization from soil or water to air appears to occur relatively slowly ( U. S. EPA, 1991a).

Very little information is available on degradation or transformation of HCBD. Under aerobic conditions, HCBD in sewage contaminated waters showed complete biodegradation ( Tabak et al., 1981). Under anaerobic soil conditions, biodegradation will not occur based on results obtained in sludge incubated under anaerobic conditions ( Johnson and Young, 1983). Estimates of the half life of HCBD in water range from 3 to 30 days in rivers and from 30 to 300 days in lakes and ground water ( Zoeteman et al., 1980).

HCBD may readily partition from the water into biological tissues, as suggested by its high log octanol: water partition coefficient ( K OW of 4.78). Laboratory and field studies have confirmed its bioaccumulation potential ( WHO, 1994; U. S. EPA, 1998a). There is no evidence that HCBD has biomagnification potential ( WHO, 1994).

HCBD is not used as a drinking water treatment chemical, and leaching from drinking water contact surfaces is not likely. Therefore, these factors are not expected to contribute to elevated levels of HCBD in drinking water.

9.4 Risk Reduction The third criterion asks if, in the sole judgment of the Administrator, regulation presents a meaningful opportunity for health risk reduction for persons served by public water systems. In evaluating this criterion, EPA looked at the total exposed population, as well as the population exposed above the estimated HRL. Estimates of the populations exposed and the levels to which they are exposed were derived from the monitoring results. These estimates are included in Chapter 4 of this document and summarized in Section 9.4.2 below.

In order to evaluate risk from exposure through drinking water, EPA considered the net environmental exposure in comparison to the exposure through drinking water. For example, if exposure to a contaminant occurs primarily through ambient air, regulation of emissions to air provides a more meaningful opportunity for EPA to reduce risk than does regulation of the contaminant in drinking water. In making a preliminary regulatory determination, the available information on exposure through drinking water ( Chapter 4) and information on exposure through other media ( Chapter 5) were used to estimate the fraction that drinking water contributes to the total exposure. The EPA findings are discussed in Section 9.4.3 below.

In making its preliminary regulatory determination, EPA also evaluated effects on potential sensitive populations, including the fetus, infants and children. Sensitive population considerations are included in section 9.4.4. HCBD   February 2003 9 11 9.4.1 Risk Reduction Criterion Conclusion Approximately 2 to 5 million people are served by systems with detections of HCBD. An estimated 10,000 of these individuals may be served by systems with detections greater than the HRL, based on Round 2 monitoring data. Sensitive populations to HCBD may include people with preexisting kidney damage and infants, though it is unlikely for human newborns to be acutely exposed to significant doses of HCBD. When average daily intakes from drinking water are compared with intakes from air, drinking water accounts for a relatively small proportion of total HCBD intake. Relative intake rates from food may be higher, however, and intakes from soil are not known. On the basis of these observations, the impact of regulating HCBD concentrations in drinking water on health risk reduction is likely to be small.

9.4.2 Exposed Population Estimates National population estimates for HCBD exposure were derived using summary statistics for Round 1 and Round 2 PWS cross sectional data ( see Table 4 2 of this document) and population data from the Water Industry Baseline Handbook ( U. S. EPA, 2000e). Summary data for exposed population estimates are provided in Table 9 2 below. An estimated 1.9 to 5 million people are served by PWSs that have detected HCBD. Of this population, approximately 1.2 million people could be exposed at one half of the HRL, based on data from Round 1 sampling; and about 5 million people could be exposed to over one half the HRL, based on Round 2 sampling. Based on the data from Round 1 sampling, about 781,000 individuals were exposed to concentrations at or above the HRL. Based on Round 2 sampling results, an estimated 10,000 persons could be exposed at or above the HRL. The Round 2 based estimate is probably a better estimate of possible exposure since the database is more recent, and more representative of the cross section population served by groundwater.

Table 9 2. National Population Estimates for HCBD Exposure via Drinking Water.

Population of Concern Round 1 Round 2 Served by PWS with detections 1,909,000 5,027,000 Served by PWSs with detections > ( 1/ 2 HRL) 1,213,000 4,965,000 Served by PWSs with detections > HRL 781,000 10,000 Source: Data taken from Table 4 2 of this document. HRL = Health Reference Level 9.4.3 Relative Source Contribution Relative source contribution analysis compares the magnitude of exposure expected via drinking water to the magnitude of exposure from intake of HCBD in other media, such as food, air, and soil. To perform this analysis, intake of HCBD from drinking water must be estimated. HCBD   February 2003 9 12 Occurrence data for HCBD in water and other media are presented in Chapter 4 and 5 of this document.

As shown in Table 4 2, the 99th percentile concentration for all samples ( i. e., those with detectable and nondetectable levels of HCBD) from Round 1 and Round 2 PWS sampling is below the MRL. As a convention, a value of half the MRL is often used as an estimate of the concentration of a contaminant in samples/ systems whose results are less than the MRL. However, for Round 1 and Round 2, States have reported a wide range of values for the MRLs ( See Section 4.2.1), and a single estimate of the MRL for HCBD is unavailable.

As an alternative, the median concentration ( 0.3 µ g/ L) for HCBD in samples with detectable levels from both rounds was used to estimate intake from drinking water. The exposure estimate for an average individual is determined by multiplying the drinking water concentration by daily water intake ( 2 liters/ day) and dividing by average adult body weight ( 70 kg), and is estimated to be 8.6 × 10 6 mg/ kg day. For children, assuming a daily water intake of 1 liter/ day and body weight of 10 kg, the exposure estimate is 3.0 × 10 5 mg/ kg day.

The estimated average daily intakes of HCBD from drinking water ( based on median concentration of detected samples) and other sources are shown in Table 9 3. The estimated food: drinking water exposure ratio is 0.03 for an adult and 0.02 for a child ( Table 9 4). The estimated air: drinking water exposure is 14 for an adult and 21 for a child. Collectively, these data indicate that intake from drinking water is low when compared to intake from air, though not necessarily when compared to possible intake from food.

Table 9 3. Comparison of Average Daily Intakes from Drinking Water and Other Media a.

Medium Adult ( ng/ kg day) Child ( ng/ kg day)

Drinking Water b 8.6 30 Food 0.15 0.24 Air 120 630 a See Chapter 5 for derivation of intakes from media other than water b Based on half the median values for detected hexachlorobutadiene concentrations in Round 1 and Round 2 Table 9 4. Ratios a of Exposures from Various Media to Exposures from Drinking Water.

Exposure Ratio Adult Child Food: Drinking Water 0.02 0.008 Air: Drinking Water 14 21 a Calculated from estimated daily intakes in Table 9 3 HCBD   February 2003 9 13 9.4.4 Sensitive Populations The target organ for HCBD is primarily the kidney. Sensitive populations to HCBD exposure may include people with preexisting kidney damage. Though it is unlikely that human newborns would be acutely exposed to significant doses of HCBD, acute exposure for young rats causes toxicity at lower levels than for adults ( Hook et al., 1983; Lock et al., 1984).

Calculation of medium specific exposure ratios ( Table 9 4) indicates that HCBD intake from air is about 14 20 fold greater than intake from water. Therefore, regulation of HCBD in drinking water would be unlikely to significantly reduce the risk to sensitive populations.

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Zoeteman, B. C. J., K. Harmsen, J. B. H. J. Linders, et al. 1980. Persistent organic pollutants in river water and groundwater of the Netherlands. Chemosphere 9: 231 249. HCBD   February 2003 A 1 APPENDIX A: Abbreviations and Acronyms ATSDR  Agency for Toxic Substances and Disease Registry CAS  Chemical Abstract Service CCL  Contaminant Candidate List CERCLA  Comprehensive Environmental Response, Compensation & Liability Act CMR  Chemical Monitoring Reform CWS  Community Water System DWEL  Drinking Water Equivalent Level EPA  Environmental Protection Agency EPCRA  Emergency Planning and Community Right to Know Act FDA  Food and Drug Administration GW  ground water HRL  Health Reference Level IRIS  Integrated Risk Information System MCL  Maximum Contaminant Level MRL  Minimum Reporting Level NAWQA  National Water Quality Assessment Program NCOD  National Drinking Water Contaminant Occurrence Database NIOSH  National Institute for Occupational Safety and Health NPDWR  National Primary Drinking Water Regulation NPL  National Priorities List NTIS  National Technical Information Service NTNCWS  Non Transient Non Community Water System ppm  part per million PWS  Public Water System SARA Title III  Superfund Amendments and Reauthorization Act SDWA  Safe Drinking Water Act SDWIS  Safe Drinking Water Information System SDWIS FED  the Federal Safe Drinking Water Information System SOC  synthetic organic compound STORET  Storage and Retrieval System SW  surface water TRI  Toxic Release Inventory UCM  Unregulated Contaminant Monitoring UCMR  Unregulated Contaminant Monitoring Regulation/ Rule URCIS  Unregulated Contaminant Monitoring Information System U. S. EPA  United States Environmental Protection Agency USGS  United States Geological Survey VOC  volatile organic compound : g/ L  micrograms per liter mg/ L  milligrams per liter > MCL  percentage of systems with exceedances > MRL  percentage of systems with detections HCBD   February 2003 B 1 APPENDIX B: Round 1 and Round 2 Occurrence Data Tables for Hexachlorobutadiene Hexachlorobutadiene Occurrence in Public Water Systems in Round 1, UCM ( 1987) results STATE TOTAL UNIQUE PWS # GW PWS # SW PWS % PWS with detections % GW PWS with detections % SW PWS with detections % PWS > HRL % GW PWS > HRL % SW PWS > HRL 99% VALUE ( µ : g/ L)

AK 665 540 130 1.50% 1.48% 1.54% 0.00% 0.00% 0.00% < 0.00 AL 131 93 42 3.05% 4.30% 0.00% 1.53% 2.15% 0.00% 0.50 AR AZ 448 407 47 0.89% 0.74% 2.13% 0.22% 0.00% 2.13% < 2.00 CA 585 571 21 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 6.00 CO 6 3 4 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.64 DC 1 0 1 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 DE 10 8 2 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 FL 112 7 105 5.36% 0.00% 5.71% 5.36% 0.00% 5.71% 5.00 GA HI 127 112 16 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.30 IA IL 213 149 64 0.47% 0.67% 0.00% 0.00% 0.00% 0.00% < 2.00 IN 357 321 37 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 2.00 KY 524 291 233 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 1.00 LA 13 9 4 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 MA MD 983 936 50 0.10% 0.11% 0.00% 0.00% 0.00% 0.00% < 0.50 MI MN 1,553 1,529 28 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 MO 85 71 14 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 20.00 MS MT NC 297 254 44 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 NE NH NJ 801 790 11 0.75% 0.76% 0.00% 0.25% 0.25% 0.00% < 1.20 NM 590 555 35 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 1.00 NV 8 7 2 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.20 NY 356 252 123 0.28% 0.40% 0.00% 0.28% 0.40% 0.00% < 5.00 OH 2,655 2,493 166 0.11% 0.12% 0.00% 0.08% 0.08% 0.00% < 2.00 SD 335 306 29 0.30% 0.33% 0.00% 0.00% 0.00% 0.00% < 0.50 TN 303 156 147 0.33% 0.64% 0.00% 0.33% 0.64% 0.00% < 0.50 TX 2 2 0 100.00% 100.00% 0.00% 100.00% 100.00% 0.00% 8.00 UT 411 391 34 1.22% 1.02% 2.94% 0.00% 0.00% 0.00% < 5.00 VI 3 0 3 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 1.00 VT WA 992 937 77 0.10% 0.11% 0.00% 0.00% 0.00% 0.00% < 0.50 WV 57 26 31 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 4.00 WY 145 116 38 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 2.00 TOTAL 12,768 11,332 1,538 0.36% 0.32% 0.65% 0.12% 0.07% 0.46% < 5.00 24 STATE S 12,284 10,980 1,385 0.35% 0.30% 0.72% 0.11% 0.06% 0.51% < 5.00 PWS = Public Water Systems; GW = Ground Water; SW = Surface Water; MRL = Minimum Reporting Limit ( for laboratory analyses); Health Reference Level = Health Reference Level, an estimated health effect level used for preliminary assessment for this review The Health Reference Level used for hexachlorobutadiene is 0.9 µ : g/ L. This is a draft value for working review only. Total Number of PWSs = the total number of public water systems with records for hexachlorobutadiene % PWS with detections, > ½ Health Reference Level, > Health Reference Level = percent of the total number of public water systems with at least one analytical result that exceeded the MRL, ½ Health Reference Level, Health Reference Level, respectively 99th Percentile Concentration = the concentration value of the 99th percentile of all analytical results ( in µ : g/ L) Median Concentration of Detections = the median analytical value of all the detections ( analytical results greater than the MRL) ( in µ : g/ L) The highlighted states are part of the URCIS ( Round 1) 24 State Cross Section. HCBD   February 2003 B 2 Hexachlorobutadiene Occurrence in Public Water Systems in Round 2, UCM ( 1993) results STATE TOTAL UNIQUE PWS # GW PWS # SW PWS % PWS with detections % GW PWS with detections % SW PWS with detections % PWS > HRL % GW PWS > HRL % SW PWS > HRL 99% VALUE ( µ : g/ L)

Tribes ( 06) 22 21 1 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 50.00 AK 625 481 144 3.36% 2.70% 5.56% 0.00% 0.00% 0.00% < 0.00 AL AR 407 319 88 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.10 AZ 68 60 8 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 1.00 CA 14 11 3 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 CO 831 619 212 0.24% 0.00% 0.94% 0.00% 0.00% 0.00% < 0.00 CT 84 43 41 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 IN 117 107 10 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 2.00 KY 121 50 71 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 2.50 LA 1,310 1,241 69 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 MA 418 344 74 0.24% 0.00% 1.35% 0.24% 0.29% 0.00% < 0.50 MD 976 920 56 0.20% 0.11% 1.79% 0.00% 0.00% 0.00% < 0.50 ME 744 676 68 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 MI 2,739 2,647 92 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 MN 1,558 1,528 30 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 MO 1,412 1,297 115 0.07% 0.08% 0.00% 0.00% 0.00% 0.00% < 1.00 MS 1 1 100.00% 100.00% 0.00% 0.00% 0.60 NC 1,775 1,585 190 0.51% 0.44% 1.05% 0.00% 0.00% 0.00% < 0.00 ND 296 258 38 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 NH NJ 7 7 0.00% 0.00% 0.00% 0.00% < 1.00 NM 720 693 27 0.14% 0.14% 0.00% 0.00% 0.00% 0.00% < 1.00 OH 2,232 2,050 182 0.04% 0.05% 0.00% 0.04% 0.00% 0.55% < 0.50 OK 790 541 249 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 OR 17 15 2 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 PA RI 115 103 12 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 1.00 SC 237 216 21 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 SD 27 19 8 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.50 TN TX 4,412 3,825 587 0.07% 0.08% 0.00% 0.05% 0.00% 0.34% 1.00 VT 1 1 0.00% 0.00% 0.00% 0.00% < 0.50 WA 2,548 2,429 119 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.00 WI 191 188 3 0.00% 0.00% 0.00% 0.00% 0.00% 0.00% < 0.30 TOTAL 24,815 22,294 2,521 0.17% 0.13% 0.56% 0.02% 0.00% 0.12% < 1.00 20 STATES 22,736 20,380 2,356 0.18% 0.13% 0.59% 0.02% 0.00% 0.13% < 1.00 PWS = Public Water Systems; GW = Ground Water; SW = Surface Water; MRL = Minimum Reporting Limit ( for laboratory analyses); Health Reference Level = Health Reference Level, an estimated health effect level used for preliminary assessment for this review The Health Reference Level used for hexachlorobutadiene is 0.9 : g/ L. This is a draft value for working review only. Total Number of PWSs = the total number of public water systems with records for hexachlorobutadiene % PWS with detections, > ½ Health Reference Level, > Health Reference Level = percent of the total number of public water systems with at least one analytical result that exceeded the MRL, ½ Health Reference Level, Health Reference Level, respectively 99th Percentile Concentration = the concentration value of the 99th percentile of all analytical results ( in : g/ L) Median Concentration of Detections = the median analytical value of all the detections ( analytical results greater than the MRL) ( in µ g/ L) The highlighted States are part of the SDWIS/ FED ( Round 2) 20 State Cross Section.