PAGE INTENTIONALLY LEFT BLANK William C. Herz Director of Scientific Programs M E M O R A N D U M TO: Product Testing Recipient FROM: William C. Herz, Director, Scientific Programs SUBJECT: Diammonium Phosphate Product Testing Dossier DATE: March 15, 2003 It is with great pleasure that The Fertilizer Institute ( TFI) announces the completion and distribution of the final product testing dossier for Diammonium Phosphate ( CAS # 7783 28 0).

As you are aware, TFI sponsored this four   year program to develop and summarize screeninglevel hazard information for high production volume ( HPV) chemicals. The data elements generated represent a broad overview of human health and ecological parameters. These include a physical  chemical characterization, environmental fate, mammalian toxicity and ecotoxicity. A health and environmental safety data summary dossier was prepared for each of the 23 materials. It summarizes the available literature data, new testing data, category description and read across data as well as provides a conclusion regarding the inherent hazards of the material.

Upon receipt of this data a 90 calendar day regulatory trigger starts within which you must update your material safety data sheets ( MS DS). Upon first product shipment you must also notify your distributors and employers once the MS DS has been updated. These regulatory requirements are detailed in 29 CFR 1910.1200( g)( 5) and 29 CFR 1910.1200( g)( 6)( i). The requirements are found in the Occupational Safety and Health Administration " Hazard Communication Standard" ( 29 CFR 1910.1200).

Please note that by receipt of this data; you agree not to distribute or sell this data beyond your own company. PAGE INTENTIONALLY LEFT BLANK HEALTH & ENVIRONMENTAL SAFETY DATA SUMMARY DOCUMENT DIAMMONIUM PHOSPHATE ( DAP) CAS NO. 7783 28 0 Prepared for:

THE FERTILIZER INSTITUTE January 27, 2003 DRAFT THE WEINBERG GROUP INC. 1220 Nineteenth St, NW, Suite 300 Washington, DC 20036 2400 e mail science@ weinberggroup. com WASHINGTON NEW YORK SAN FRANCISCO BRUSSELS PARIS PAGE INTENTIONALLY LEFT BLANK Diammonium Phosphate ( DAP) CAS # 7783 28 0 ii TABLE OF CONTENTS Page EXECUTIVE OVERVIEW.......................................................................................................................... 1 SIDS DATA PROFILE.................................................................................................................... 8 SIDS DATA SUMMARY............................................................................................................... 9 1. GENERAL INFORMATION............................................................................................... 11 2. PHYSICAL CHEMICAL DATA......................................................................................... 15 3. ENVIRONMENTAL FATE AND PATHWAYS................................................................ 18 4. ECOTOXICITY.................................................................................................................... 19 5. TOXICITY............................................................................................................................ 27 6. REFERENCES ..................................................................................................................... 34 APPENDICES Appendix A SIDS Data Availability Summary Appendix B SIDS Data Summaries for the Phosphate Compounds Category: Diammonium Phosphate, Liquid Polyphosphate, Monoammonium Phosphate, and Super Phosphates ACRONYMS AND ABBREVIATIONS BCF Bioconcentration Factor bw Body Weight DAP Diammonium Phosphate DOT Department of Transportation FDA U. S. Food and Drug Administration g/ L Grams per Liter GLP Good Laboratory Practices GTSP Granular Triple Super Phosphate g/ mL Grams per Milliliter HSDB Hazardous Substance Data Bank IPCS International Programme for Chemical Safety KNO3 Potassium Nitrate Koc Organic Carbon Partition Coefficient Kow Octanol/ Water Partition Coefficient LC50 Median Lethal Concentration LD50 Median Lethal Dose LOAEL Lowest Observable Adverse Effect Level LOEC Lowest Observable Effect Concentration LOEL Lowest Observable Effect Level M Molar Diammonium Phosphate ( DAP) CAS # 7783 28 0 iii MAP Monoammonium Phosphate mg/ kg Milligrams per Kilogram mg/ kg/ day Milligrams per Kilogram per Day mg/ L Milligrams per Liter MHb Methyl Hemoglobin mm Hg Millimeters of Mercury mmol/ L Millimoles per Liter NaNo3 Sodium Nitrate NFPA National Fire Prevention Association ( NH4) 2NO3 Ammonium Nitrate NIOSH National Institute for Occupational Safety and Health NO3 Nitrate NOAEL No Observable Adverse Effect Level NOEC No Observable Effect Concentration NOEL No Observable Effect Level OECD Organisation for Economic Co operation and Development Pa Pascal ppm Parts per Million SCAS Semi Continuous Activated Sludge SIDS Screening Information Data Set SSP Single Super Phosphate TLm Median Toxicity Level TLV Threshold Limit Value TFI The Fertilizer Institute UAN Urea Ammonia Nitrogen Diammonium Phosphate ( DAP) CAS # 7783 28 0 1 EXECUTIVE OVERVIEW I. Introduction The Fertilizer Institute, on behalf of its member companies, initiated a Product Testing Project to collect, review, summarize, and where necessary develop additional health and environmental safety data for 23 of its high production volume inorganic fertilizer materials. These data and summaries provide valuable information that can be used to update Material Safety Data Sheets, answer customers' questions, and support product stewardship efforts. The chemical industry is also participating in a voluntary program of comparable scope for high production volume organic chemicals. 1 The 23 fertilizer materials were divided into five categories ( i. e., ammonia compounds, nitrate compounds, phosphate compounds, salts and acids) based on their primary constituents as shown in Table 1. The use of categories is a recognized and accepted method that allows health and environmental safety data from one chemical in the category to be used to represent one or more other related chemicals in the category ( USEPA 1999). The key is to find similar, or at least predictable, patterns and trends among the chemicals in a category. In this way, data can be pooled, resources are optimized, and fewer animals are used in testing, all without losing the ability to evaluate the hazards and safety of the individual chemicals. Note that some of the materials fall into more than one category ( e. g., diammonium phosphate [ DAP] is in both the phosphate and ammonia categories).

Searches were conducted using on line databases, standard scientific data compendia, and other published sources for toxicity, ecotoxicity, environmental fate, and physical chemical properties. The collected data were reviewed for quality and acceptability and then summarized according to the Organization for Economic Cooperation and Development ( OECD) Screening Information Data Set ( SIDS) dossier format ( OECD 1997). The OECD countries ( including the United States) have agreed on a set of tests and on types of data that are generally necessary to characterize the chemical behavior and potential hazards of chemicals released into the environment. The OECD SIDS dossier was chosen as a standard format for the TFI Product Testing Project in order that it would be scientifically defensible, broadly applicable and easily understandable to a wide range of stakeholders.

The following sections of this Executive Overview provide the rationale for development of the Phosphate Compounds category ( Section II); a synopsis of the available data related to the physical chemical properties, environmental fate, ecotoxicity and toxicity of the phosphate compounds in this category ( Section III); and a conclusion regarding the adequacy of the data to sufficiently characterize the category and the need for additional testing ( Section IV).

The data for diammonium phosphate ( DAP) are summarized in the Chemical Profile and Data Summary tables. Because the evaluation of data adequacy relies on a category approach, the Data Summary table references Appendix B when data are available for one or more of the other materials in the category for those data elements where no DAP data are available. Appendix B provides a summary of the data for all of the phosphate compounds in the category. The 1 HPV Chemical Challenge Program; USEPA 1999 ( http:// www. epa. gov/ opptintr/ chemrtk/ volchall. htm) Diammonium Phosphate ( DAP) CAS # 7783 28 0 2 individual studies for DAP itself are presented in subsequent pages of this document. Separate data summary documents are available for each of the phosphate compounds in the category.

II. Rationale for the Phosphate Compounds Category The phosphate compounds category for fertilizer materials includes diammonium phosphate ( DAP), monoammonium phosphate ( MAP), liquid polyphosphate, single superphosphate ( SSP), and granular triple superphosphate ( GTSP) 2. These compounds are grouped because of chemical composition similarities; phosphate being a primary component. All four compounds in the category contain phosphorus, hydrogen and oxygen. Three of the compounds also contain nitrogen. In additional, the four compounds have similar and generally predictable patterns of behavior in the environment as well as toxicological properties.

Phosphate compounds disassociate in water, and therefore may be regarded as degradable ( European Commission 2000a). They are used by all living organisms and both the anion and cation are nutrients for algae ( European Commission 2000b). The primary contributor to aquatic toxicity appears to be the un ionized ammonia component of DAP and MAP, although excess phosphate may also have an effect ( Johnson and Sanders 1977). As a nutrient, phosphate may also stimulate growth in algae ( Aufderheide and Bussard 2000). When GTSP is applied to soil, the water soluble monocalcium phosphate rapidly dissolves into the soil solution and is quickly precipitated as available dicalcium phosphate. Inorganic phosphates are generally retained by most soils in fixed forms and therefore little is lost by leaching ( European Commission 2000a). Liquid polyphosphate fertilizers behave essentially as salts in soil ( Lohry 2001).

Phosphate compounds are Generally Recognized As Safe ( GRAS) by the U. S. Food and Drug Administration ( 21 CFR 582.1141; Bhat and Ramaswamy 1993) which allows them to be used as food and color additives. Phosphate is an essential nutrient required by all organisms for proper metabolism. Orthophosphates in general are absorbed from, and to a limited extent secreted into, the gastrointestinal tract. The transport of phosphate from the lumen of the gut is an active, energy dependent process, and there are factors that appear to modify the degree of its intestinal absorption. Vitamin D stimulates phosphate absorption, and this effect has been reported to precede the action of the vitamin on transport of calcium ion. In general, in adults, about two thirds of the ingested phosphate is absorbed from the bowel, and that which is absorbed from the gut is almost entirely excreted into the urine.

2 SSP and GTSP are combined into a single Health and Environmental Safety Data Summary Document. Diammonium Phosphate ( DAP) CAS # 7783 28 0 3 III. Summary of Data Available for the Phosphate Compounds Category Detailed data summaries for phosphate compounds are included in subsequent sections of this Health and Environmental Safety Data Summary Document for DAP. These data are briefly summarized here.

Physical Chemical Data The density of phosphate compounds varies from 0.93 1.83 g/ L. All phosphate compounds are highly soluble in water with solubility ranging from 18 588 g/ L at temperatures from 0 to 30 ° C. The one vapor pressure value reported for DAP indicates low volatility (< 100 Pa at 20 ° C). No specific data on the octanol water partition coefficient ( Kow) are available, but based on the high water solubility it is expected that Kow and bioaccumulation potential would be low, although the body does absorb phosphates as necessary to carry out vital functions. These compounds dissociate and do not undergo oxidation reduction reactions so redox potentials are not applicable.

Environmental Fate and Pathway Little direct environmental fate testing has been conducted with the phosphate compounds, largely because such compounds generally dissociate in solution and therefore photodegradation and biodegradation mechanisms are less important. However, phosphates may be regarded as biodegradable, as they are utilized by all living organisms. The phosphorus cycle is well understood ( e. g. see www. ppi far. org/ ppiweb/ ppibase. nsf/$ webindex/ article= 678CA758852569B5005C148685E4A99F).

Ecotoxicity Acute 96 hour studies have been reported in the literature on various fish species. These reported LC50 values range from 90 5,900 mg/ L for DAP and other compounds in the phosphate category. Additional, acute fish toxicity studies have been conducted for MAP and liquid polyphosphate according to OECD protocols and under Good Laboratory Practice ( GLP) conditions. Results indicate no toxicity at the highest nominal concentration ( 100 mg/ L) tested in both tests. MAP and liquid polyphosphate concentrations were calculated based on measurements of total phosphate. For the high concentration in each test, the measured concentrations were 85.9 and 101 mg/ L of MAP and liquid polyphosphate, respectively. Acute studies with Daphnia magna were not available for members of the phosphate category, but studies have been conducted with commercial grade superphosphate on a similar daphnid species, Daphnia carinata. These 72 hour studies resulted in LC50 values of approximately 1,800 mg/ L at both 22 and 30 º C. Results from acute toxicity testing of other aquatic invertebrates have also been reported, with LC50 values ranging from about 1000 to over 5,000 mg/ L for DAP and superphosphates. Based on the standard Federal Insecticide Fungicide and Rodenticide Act ( FIFRA) acute toxicity ratings for fish and Daphnia ( below), the compounds in this category are considered slightly toxic to practically non toxic. Diammonium Phosphate ( DAP) CAS # 7783 28 0 4 EC/ LC50 ( mg/ L) Toxicity Description < 0.1 Very Highly Toxic 0.1 1 Highly Toxic 1 10 Moderately Toxic 10 100 Slightly Toxic > 100 Practically Non Toxic Additional studies have been conducted to evaluate the toxicity of DAP and GTSP to an alga species, Selenastrum capricornutum. Both materials were tested according to OECD protocols under GLP conditions. The resultant 72 hr NOECs were 97.1 and 87.6 mg/ L, for DAP and GTSP, respectively. No adverse inhibitory effects were observed in either test. Some stimulation of growth was noted in both tests, with resultant NOEC values of 3.57 and 21.6 mg/ L for DAP and GTSP respectively. This effect is consistent with the known stimulatory ( nutrient) effect of phosphate compounds and reflects the phenomenon that some level of phosphate is essential ( e. g., fisheries productivity is dependent on sufficient nutrient availability) but excess nutrient levels can lead to overproduction.

Mammalian Toxicity Acute toxicity The only toxicity study available from the literature was one in which ewes were dosed with a granular preparation of superphosphate. The reported LD50 for this study was 5,000 6,000 mg/ kg bw. To provide additional data for the category, additional studies were initiated for DAP, MAP, and liquid polyphosphate using the OECD " up and down" protocol under GLP conditions. For all three compounds, rats received an initial dose of 2000 mg/ kg bw by oral gavage. All animals survived, gained weight, and appeared active and healthy throughout the study period, with no signs of toxicity observed for any of the test materials. Similarly, additional acute toxicity studies for exposure via the dermal route were conducted on DAP, MAP, and liquid polyphosphate using the OECD limit test protocol under GLP conditions. In dermal exposures of 5,000 mg/ kg bw, no signs of toxicity were observed and all animals survived, gained weight, and appeared active and healthy throughout the tests. Based on the standard FIFRA acute toxicity ratings for mammals ( below), the compounds in this category are considered to be of low to very low toxicity ( 40 CFR 156.62).

Toxicity Category I II III IV Toxicity Rating High Moderate Low Very Low Oral LD50   50 mg/ kg > 50 500 mg/ kg > 500 5000 mg/ kg > 5000 mg/ kg Dermal LC50   200 mg/ kg > 200 2000 mg/ kg > 2000 20,000 mg/ kg > 20,000 mg/ kg Inhalation LC50   0.2 mg/ L > 0.2 2 mg/ L > 2 20 mg/ L > 20 mg/ L Diammonium Phosphate ( DAP) CAS # 7783 28 0 5 Skin and eye irritation No specific animal studies are available for skin and eye irritation. Data for the dermal studies described above indicate that skin exposures are not a significant concern. However, dust from the solid materials and concentrated solutions of the liquid materials can be mild irritants.

Genotoxicity In vitro bacterial and non bacterial genotoxicity studies have been conducted on DAP and GTSP as representatives of the category. Using the OECD bacterial reverse mutation assay ( Ames) protocol under GLP conditions, S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 were tested at concentrations of 50, 150, 500, 1,500, and 5,000 µ g/ plate. Using the OECD mammalian chromosome aberration test under GLP conditions, Chinese hamster ovaries were tested at concentrations from 185 to 1,480 µ g/ mL. In all of the in vitro genotoxicity studies, results were negative in all cases both with and without metabolic activation. One in vivo study is reported in the literature from 1988 in which single superphosphate was incorporated into the food of mice at 500 mg/ day for 7 days. Chromosomal aberrations were observed in the bone marrow and the authors concluded that single superphosphate was clastogenic and possibly mutagenic. Given the high doses of this study and the lack of effect noted in the in vitro studies conducted under GLP conditions, the genotoxicity potential appears to be low.

Repeated dose, reproductive and developmental toxicity Studies have been conducted on DAP and GTSP using the OECD Guideline 422 combined protocol that provides data on repeated dose exposures as well as reproductive and developmental endpoints. Doses of 250, 750, and 1500 mg/ kg/ day were given by gavage to male and female rats daily ( 7 days/ week). Animals were divided between separate toxicity and reproductive subgroups. The exposure period for the toxicity subgroup was 35 days, while the exposure period for the reproductive subgroup was at most 28 days among males and 53 days among females. No treatment related mortality or signs of overt clinical toxicity were observed in either subgroup. In the toxicity subgroup, several hematological, clinical chemistry, and histopathological parameters among the low, mid, and high dose animals showed effects. In the reproductive subgroup, effects on body weight and food consumption were observed in a non dose related manner. No effects on offspring were observed in either study. For GTSP, the resulting NOAEL for reproductive/ developmental toxicity was 750 mg/ kg/ day. The resultant LOAELs were 250 and 1,500 mg/ kg/ day for the general toxicity and reproductive/ developmental toxicity, respectively. For DAP, the NOAEL for general toxicity was 250 mg/ kg/ day and for reproductive/ developmental toxicity was 1,500 mg/ kg/ day. The LOAELs were 500 and > 1,500 mg/ kg/ day for the general toxicity and reproductive/ developmental toxicity, respectively.

IV. Conclusion for the Phosphate Compounds Category A substantial amount of data has been produced for the compounds in the phosphate compounds category. These data include GLP studies on the acute oral and dermal toxicity of DAP, MAP, and liquid phosphate and bacterial and non bacterial genotoxicity studies on DAP and GTSP. Diammonium Phosphate ( DAP) CAS # 7783 28 0 6 Additionally, GLP acute fish studies were conducted on liquid polyphosphate and MAP, and GLP algae studies were conducted on DAP and GTSP. Combined repeat dose/ reproductive/ developmental studies were also conducted on DAP and GTSP. The results indicate that these compounds are slightly toxic to practically non toxic to aquatic organisms and of low to very low toxicity to mammals. The compounds in the phosphate category are adequately characterized. Diammonium Phosphate ( DAP) CAS # 7783 28 0 7 TABLE 1: CATEGORIES FOR PRODUCT TESTING PROJECT CATEGORY COMPOUND CAS NUMBER Ammonia Compounds Anhydrous ammonia Aqua ammonia Ammonium nitrate Ammonium sulfate Ammonium thiosulfate Nitrogen solutions ( UAN)* Ammonium phosphate sulfate Diammonium phosphate ( DAP) Monoammonium phosphate ( MAP) Urea 7664 41 7 1336 21 6 6484 52 2 7783 20 2 7783 18 8 15978 77 5 12593 60 1 7783 28 0 7722 76 1 57 13 6 Nitrate Compounds Sodium nitrate Ammonium nitrate Potassium nitrate Potassium sodium nitrate Nitrogen solutions ( UAN)* 7631 99 4 6484 52 2 7757 79 1 7757 79 1/ 7631 99 4 15978 77 5 Phosphate Compounds Diammonium phosphate ( DAP) Monoammonium phosphate ( MAP) Liquid polyphosphate Single superphosphate** Granular triple superphosphate** 7783 28 0 7722 76 1  8011 76 5 65996 95 4 Salts Potassium chloride Potassium magnesium sulfate Potassium nitrate Potassium sodium nitrate Potassium sulfate Calcium sulfate 7447 40 7 14168 73 1 7757 79 1 7757 79 1/ 7631 99 4 7778 80 5 7778 18 9 Acids Phosphoric acid Nitric acid Sulfuric acid 7664 38 2 7697 37 2 7664 93 9 * = Nitrogen solutions are represented largely by Urea Ammonia Nitrogen ( UAN; 15978 77 5) ** = Single superphosphate and granular triple superphosphate are combined into a single dossier.  = No CAS number readily available Diammonium Phosphate ( DAP) CAS # 7783 28 0 8 V. REFERENCES CITED 21 CFR 582.1141 as cited in Hazardous Substances Data Bank ( HSDB). 1999. Calcium Superphosphate. National Library of Medicine, Bethesda, MD.

40 CFR 156.62. Toxicity Category.

Aufderheide, J. A. and Bussard, J. B. 2000. Toxicity of Diammonium Phosphate ( DAP) to the Unicellular Green Alga, Selenastrum Capricornutum. ABC Study No. 46207.

Bhat, M. R. and Ramaswamy, C. 1993. Effect of ammonia, urea and diammonium phosphate ( DAP) on lung functions in fertilizer plant workers. Indian J. Physiol. Pharmacol. 37: 222 224.

Gilman. 1990. Pharm Basis Therap 8th Ed. p. 1501 as cited in HSDB. 1999. Calcium Superphosphate. National Library of Medicine, Bethesda, MD.

European Commission. 2000a. Superphosphate, Concd. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

European Commission. 2000b. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

Johnson, W. W. and Sanders, H. O. 1977. Chemical forest fire retardants: Acute toxicity to five freshwater fishes and a scud. Technical Papers of the U. S. Fish and Wildlife Service.

Lohry, R. 2001. Ortho vs. poly. The Fluid Journal. Issue # 35, 9( 4): 1 3.

OECD. 1997. SIDS Manual. OECD Secretariat, 3rd Revision, July 1997.

USEPA. 1999. Development of Chemical Categories in the HPV Challenge Program. www. epa. gove/ chemrtk/ catdoc29. pdf. Diammonium Phosphate ( DAP) CAS # 7783 28 0 9 SIDS DATA PROFILE Date: January 27, 2003 1.01 A. CAS No. 7783 28 0 1.01 C. CHEMICAL NAME ( OECD NAME) Diammonium phosphate 1.01 D CAS DESCRIPTOR Diammonium phosphate 1.01 G STRUCTURAL FORMULA ( NH4) 2HPO4 OTHER CHEMICAL IDENTITY INFORMATION N/ A 1.5 QUANTITY > 1,000,000 tonnes 1.7 USE PATTERN Ammonium phosphates, particularly DAP, are the most popular fertilizers used worldwide. Other, more limited, uses of DAP include textile processing, flame retardants, laboratory chemicals, intermediates, food additives, and corrosion inhibitors. 1.9 SOURCES AND LEVELS OF EXPOSURE Low human exposure is expected because DAP is manufactured in closed systems. Exposure to dusts and direct contact with the material is possible during fertilizer application. ISSUES FOR DISCUSSION The data for diammonium phosphate ( DAP) should be evaluated in combination with the other materials in the phosphate category, especially monoammonium phosphate ( MAP). Diammonium Phosphate ( DAP) CAS # 7783 28 0 10 SIDS DATA SUMMARY Date: January 27, 2003 DIAMMONIUM PHOSPHATE ( CAS NO. 7783 28 0) SPECIES PROTOCOL RESULTS PHYSICAL CHEMICAL DATA 2.1 Melting Point 155 ° C 2.2 Boiling Point Decomposes 2.3 Density 0.93 1.619 g/ mL at 20oC 2.4 Vapor Pressure < 100 Pa at 20 ° C 2.5 Octanol/ Water Partition Coefficient See Appendix B* 2.6A Water Solubility 588 g/ L at 20 ° C 2.6B pH Value ~ 8 2.7 Flash Point Not applicable 2.8 Auto Flammability Not flammable 2.9 Flammability Not flammable 2.10 Explosive Properties Not explosive 2.11 Oxidizing Properties Not an oxidizer 2.12 Oxidation: Reduction Potential See Appendix B* 2.13A Additional data See text ENVIRONMENTAL FATE and PATHWAY 3.1.1 Photodegradation No data available 3.1.2 Stability in Water Stable 3.1.3 Stability in Soil Stable 3.3.2 Distribution Calculated, Fugacity Level III 6.5 x 10 15% to air 45.3% to water 54.6% to soil 0.0755% to sediment 3.5 Biodegradation Phosphorus cycle is well understood 3.7 Bioaccumulation Does not bioaccumulate ECOTOXICITY 4.1 Acute Toxicity to Fish Coho salmon, Chinook salmon, Rainbow trout, Bluegill, Largemouth bass, Tilapia, Fathead minnow 96 hrs LC50 = 90 1,875 mg/ L 4.2 Acute Toxicity to Aquatic Invertebrates Daphnia magna Amphipod Snail, Worm 96 hrs 96 hrs See Appendix B* LC50 = 40 52 mg/ L LC50 = 1,005 2,472 mg/ L 4.3 Toxicity to Aquatic Plants ( Algae) Selenastrum capricornutum 72 hrs NOEC ( toxicity) = 97.1 mg DAP/ L NOEC ( stimulation) = 3.57 mg DAP/ L 4.4 Toxicity to Bacteria No data available 4.5.1 Chronic Toxicity to Fish No data available 4.5.2 Chronic Toxicity to Aquatic Invertebrates No data available 4.6.1 Toxicity to Soil Dwelling Organisms No data available 4.6.2 Toxicity to Terrestrial Plants See Appendix B* 4.6.3 Toxicity to Other Non Mammalian Terrestrial Species No data available * See Appendix B results for data on other chemicals in the phosphate category. Diammonium Phosphate ( DAP) CAS # 7783 28 0 11 DIAMMONIUM PHOSPHATE ( CAS NO. 7783 28 0) SPECIES PROTOCOL RESULTS TOXICITY 5.1.1 Acute Oral Toxicity Rat OECD 425 LD50 > 2,000 mg/ kg bw 5.1.2 Acute Inhalation Toxicity No data available 5.1.3 Acute Dermal Toxicity Rat OECD 402 LD50 > 5000 mg/ kg bw 5.1.4 Acute Toxicity, Other Routes No data available 5.2.1 Skin Irritation/ Corrosion Irritant 5.2.2 Eye Irritation/ Corrosion Irritant 5.3 Skin Sensitization No data available 5.4 Repeated Dose Toxicity Rat OECD 422 NOAEL = 250 mg/ kg/ day 5.5 Genetic Toxicity in vitro . Gene mutation Salmonella typhimurium Bacterial reverse mutation assay ( OECD 471) Negative . Chromosomal aberration Chinese Hamster Ovaries Chromosome aberration test ( OECD 473) Negative 5.6 Genetic Toxicity in vivo See Appendix B* 5.7 Carcinogenicity No data available 5.8 Toxicity to Reproduction Rat OECD 422 NOAEL = 1500 mg/ kg/ day 5.9 Developmental Toxicity/ Teratogenicity Rat OECD 422 NOAEL = 1500 mg/ kg/ day 5.10 Additional Information See text 5.11 Human Experience See text 1.8 Occupational Exposure Limits TLV as inert dust 15 mg/ m3 * See Appendix B results for data on other chemicals in the phosphate category. Diammonium Phosphate ( DAP) CAS # 7783 28 0 12 1. GENERAL INFORMATION 1.01 SUBSTANCE INFORMATION A. CAS number 7783 28 0 B. Name ( IUPAC name) Diammonium hydrogenorthophosphate C. Name ( OECD name) Diammonium phosphate ( DAP)

D. CAS Descriptor Diammonium phosphate ( DAP)

E. EINECS Number 231 987 8 F. Molecular Formula H9N2O4P G. Structural Formula ( NH4) 2HPO4 SMILES: N( H)( H)( H)( H) OP(= O)( O) ON( H)( H)( H)( H)

H. Substance Group Not applicable I. Substance Remark Not applicable J. Molecular Weight 132.06 1.02 OECD INFORMATION A. Sponsor Country Not applicable B. Lead Organization Not applicable C. Name of Responder Name: Mr. William C. Herz, Director of Scientific Programs Address/ Phones: The Fertilizer Institute Union Center Plaza 820 First Street, NE, Suite 430 Washington, DC 20002 USA Tel: ( 202) 962 0490 Fax: ( 202) 962 0577 Diammonium Phosphate ( DAP) CAS # 7783 28 0 13 1.1 GENERAL SUBSTANCE INFORMATION A. Type of Substance element [ ]; inorganic [ X]; natural substance [ ]; organic [ ]; organometallic [ ]; petroleum product [ ]

B. Physical State ( at 20 ° C and 1.013 hPa)

gaseous [ ]; liquid [ ]; solid [ X]

C. Purity > 98%; pure DAP is 21.19% N, 53.76% P2O5 1.2 SYNONYMS Ammonium phosphate, dibasic Diammonium hydrogenorthophosphate Diammonium hydrogenphosphate Diammonium phosphate DAP Phosphoric acid, diammonium salt Ammonium hydrogen phosphate 1.3 IMPURITIES Remarks: None identified 1.4 ADDITIVES Remarks: None identified 1.5 QUANTITY ( a) Remarks: > 1,000,000 tonnes References: European Commission 2000. Ammonium sulfate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

( b) Remarks: 18,700,000 tonnes ( 1992) Reference: United Nations Industrial Development Organization ( UNIDO) and International Fertilizer Development Center ( IFDC). 1998. Fertilizer Manual. Kluwer Academic Publishers, The Netherlands. Diammonium Phosphate ( DAP) CAS # 7783 28 0 14 1.6 LABELING AND CLASSIFICATION Remarks: No specific labeling required.

1.7 USE PATTERN A. General Type of Use: Category:

( a) main Wide dispersive use industrial Agricultural use Fertilizers ( b) main Wide and nondispersive uses industrial Chemical use Textile processing, flame retardants, laboratory chemicals, intermediates, food additives, and corrosive inhibitors Remarks: Ammonium phosphates, particularly DAP, are the most popular fertilizers worldwide because of their high analysis and good physical properties. Reference: 1) European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition. 2) United Nations Industrial Development Organization ( UNIDO) and International Fertilizer Development Center ( IFDC). 1998. Fertilizer Manual. Kluwer Academic Publishers, The Netherlands.

B. Uses in Consumer Products Remarks: DAP may be a component of lawn and garden fertilizers.

1.8 OCCUPATIONAL EXPOSURE LIMIT VALUE Exposure limit value Type: OSHA PEL Value: 15 mg/ m3 total dust; 5 mg/ m3 respirable fraction. Remark: No specific limit has been set, however, the federal OSHA PEL for particulates not otherwise regulated applies to all fertilizer dusts. Regulated limits may vary in local jurisdictions. Diammonium Phosphate ( DAP) CAS # 7783 28 0 15 1.9 SOURCES OF EXPOSURE Remarks: Exposures are expected to be limited because DAP is manufactured in closed systems. DAP can be absorbed into the body by inhalation of its aerosol or dust, or after direct exposure to skin or eyes. Engineering controls such as mechanical ventilation, process or personnel enclosure, control of process conditions, and process modifications significantly reduce exposure. Local exhaust ( ventilation) control as close to the point of generation is both the most economical and safest method to minimize personnel exposure to airborne concentrations. Personal protective equipment includes neoprene or nitrile gloves, dust masks or fume hoods as appropriate, chemical safety goggles, and impervious apron, sleeves and boots. Field exposure to workers is possible when handling and using on farms as a fertilizer. However, fertilizers are applied by mechanical spreaders, which reduces contact exposure. Environmental releases are controlled at the manufacturing plant. Gaseous emissions are low due to use of scrubbers and liquid effluent is recovered as much as possible. Exposure to environmental receptors is dependent on the amount used as fertilizer on fields, the climatic conditions, and the hydrological conditions of the area of application. Phosphate materials are common in the environment and are essential nutrients for both plants and animals. References: 1) HSDB. 1999. Diammonium phosphate. National Library of Medicine, Bethesda, MD. 2) IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic.

1.10 ADDITIONAL REMARKS A. Options for disposal Remarks: DAP should be disposed of in accordance with federal, state and local environmental control regulations. Generally a sufficient method is to sweep spilled substance into covered containers, and wash away the remainder with plenty of water. References: IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic. Diammonium Phosphate ( DAP) CAS # 7783 28 0 16 2. PHYSICAL CHEMICAL DATA 2.1 MELTING POINT Value: 155 ° C Decomposition: Yes [ X] No [ ] Ambiguous [ ] Sublimation: Yes [ ] No [ X] Ambiguous [ ] Method: Not specified GLP: Yes [ ] No [ ] ? [ X] References: Lide, D. R. 1992. CRC Handbook of Chemistry and Physics. Boston: CRC Press.

2.2 BOILING POINT Remarks: Not applicable. Decomposes References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition. IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic.

2.3 DENSITY ( Relative Density)

( a) Type: Bulk density [ ]; Density [ X]; Relative Density [ ] Value: 1.619 g/ mL Temperature: 20 ° C Method: Not specified GLP: Yes [ ] No [ ] ? [ X] References: Lide, D. R. 1992. CRC Handbook of Chemistry and Physics. Boston: CRC Press.

( b) Type: Bulk density [ X]; Density [ ]; Relative Density [ ] Value: 0.93 g/ mL Temperature: 20 ° C Method: Not specified GLP: Yes [ ] No [ ] ? [ ] Remarks: Granular product for fertilizers References: Lewis, Jr., R. J. 1992. Sax's Dangerous Properties of Industrial Materials. 8th ed. Vol. II. New York: Van Nostrand Reinhold. Diammonium Phosphate ( DAP) CAS # 7783 28 0 17 2.4 VAPOR PRESSURE ( a) Value: < 100 Pa Temperature: 20 ° C Method: Not specified GLP: Yes [ ] No [ ] ? [ X] Remarks: Ammonia gas over granular fertilizer product. References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

( b) Remarks: Evaporation at 20oC is negligible. References: IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic.

2.5 PARTITION COEFFICIENT logPow Remarks: No specific data available. Based on water solubility it is expected that the log Pow would be very low.

2.6 WATER SOLUBILITY A. Solubility ( a) Value: 5.88 x 105 mg/ L Temperature: 20 ° C Description: Miscible [ ]; Of very high solubility [ X]; Of high solubility [ ]; Soluble [ ]; Slightly soluble [ ] Of low solubility [ ]; Of very low solubility [ ]; Not soluble [ ] Method: Not specified GLP: Yes [ ] No [ ] ? [ X] Remarks: Practically insoluble in ethanol, acetone, and ammonia References: Budavari, S. 1996. The Merck Index. Whitehouse Station: Merck Research Laboratories.

B. pH Value, pKa Value pH Value: ~ 8 Concentration: 1% Temperature: 20 ° C Method: Not specified GLP: Yes [ ] No [ ] ? [ X] Diammonium Phosphate ( DAP) CAS # 7783 28 0 18 References: Budavari, S. 1996. The Merck Index. Whitehouse Station: Merck Research Laboratories.

2.7 FLASH POINT ( liquids)

Remarks: Not applicable 2.8 AUTO FLAMMABILITY ( solid/ gases)

Remarks: Not flammable References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

2.9 FLAMMABILITY Remarks: Not flammable References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

2.10 EXPLOSIVE PROPERTIES Remarks: Not explosive References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

2.11 OXIDIZING PROPERTIES Remarks: No known oxidizing properties References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

2.12 OXIDATION: REDUCTION POTENTIAL Remarks: No data available Diammonium Phosphate ( DAP) CAS # 7783 28 0 19 2.13 ADDITIONAL DATA Remarks: The substance decomposes on heating above 100oC, on contact with strong bases, producing toxic and corrosive fumes including ammonia, nitrogen oxides and phosphorous oxides. The solution in water is a weak base. Reacts vigorously with strong acids and strong oxidants. Gradually gives off ammonia on exposure to air. References: IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic.

3. ENVIRONMENTAL FATE AND PATHWAYS 3.1 STABILITY 3.1.1 PHOTODEGRADATION Remarks: No data available 3.1.2 STABILITY IN WATER Remarks: Can persist in natural water. Both the anion and cation are nutrients for algae. References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

3.1.3 STABILITY IN SOIL Remarks: Both the anion and cation are nutrients for plants. References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

3.2 MONITORING DATA ( ENVIRONMENTAL)

Remarks: No data available. Diammonium Phosphate ( DAP) CAS # 7783 28 0 20 3.3 TRANSPORT AND DISTRIBUTION BETWEEN ENVIRONMENTAL COMPARTMENTS INCLUDING ESTIMATED ENVIRONMENTAL CONCENTRATIONS AND DISTRIBUTION PATHWAYS 3.3.1 TRANSPORT Remarks: No data available.

3.3.2 THEORETICAL DISTRIBUTION ( FUGACITY CALCULATION)

Method: Fugacity Level III ( Mackay type) Mass Distribution by Environmental Compartment: Air 6.5 x 10 15% Water 45.3% Soil 54.6% Sediment 0.0755% References: USEPA. 2000. EPISUITE Estimation Program V. 3.10. US Environmental Protection Agency.

3.4 IDENTIFICATION OF MAIN MODE OF DEGRADABILITY IN ACTUAL USE Remarks: No data available.

3.5 BIODEGRADATION Remarks: The phosphorus cycle is well understood.

3.6 BOD5, COD OR RATIO BOD5/ COD Remarks: No data available.

3.7 BIOACCUMULATION Remarks: Will not bioaccumulate.

4. ECOTOXICITY 4.1 ACUTE/ PROLONGED TOXICITY TO FISH ( a) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Opensystem [ X]; Closed system [ ] Diammonium Phosphate ( DAP) CAS # 7783 28 0 21 Species: Oncorhynchus kisutch ( Coho salmon), Salmo gairdneri ( Rainbow trout), Pimephales promelas ( Fathead minnows), Lepomis macrochirus ( Bluegills), Micropterus salmoides ( Largemouth bass) Exposure period: 96 hour Results: LC50 ( Coho salmon fry; 11oC) = 90 580 mg/ L LC50 ( Coho salmon fingerling; 11oC) = 1,000> 1,500 mg/ L LC50 ( Rainbow trout fry; 11oC) = 150 700 mg/ L LC50 ( Rainbow trout fingerling; 11oC) = 1,000 mg/ L LC50 ( Fathead minnow; 21oC) = 940> 1,000 mg/ L LC50 ( Bluegills; 21oC) = > 1,500 mg/ L LC50 ( Largemouth bass; 21oC) = 1,160> 1,500 mg/ L Analytical monitoring: Yes [ ]; No [ X]; ? [ ] Method: Static tests were performed in reconstituted water with a pH of 7.4. Fish were acclimated for at least 14 days before testing. GLP: Yes [ ] No [ ] ? [ X] Test substance: Chemical forest fire retardant formulations: Fire Trol 100 and Fire Trol 931 ( ammonium sulfate or polyphosphate with an attapulgite thickener), and Phos Chek 202 and Phos Chek 259 ( diammonium phosphate with a guargum derivative thickener) were mixed with water. Remarks: In all formulations, the toxic effects generally manifested within 24 h of exposure and LC50 values at 24 and 96 h were not substantially different. The primary contributor to the acute toxicity of the compounds is believed to be un ionized ammonia. References: Johnson, W. W. and Sanders, H. O. 1977. Chemical forest fire retardants: Acute toxicity to five freshwater fishes and a scud. Technical Papers of the U. S. Fish and Wildlife Service.

( b) Type of test: Static [ X]; Semi static [ X]; Flow through [ ]; Opensystem [ X]; Closed system [ ] Species: Sarotherodon mossambicus ( Tilapia) Exposure period: 96 hour Results: LC50 ( pH 7.4; 28oC) = 550 mg/ L Analytical monitoring: Yes [ X]; No [ ]; ? [ ] Method: For the mortality study, ten individuals were exposed in static systems to concentrations of DAP ( 100 to 1000 mg/ L). For the food utilization and growth study, five fish were exposed to DAP concentrations ranging from 200 to 500 mg/ L These fish were fed twice a day, and the culture medium was changed every two days. GLP: Yes [ ] No [ ] ? [ X] Test substance: ( NH4) 2HPO4 ( fertilizer grade DAP; NPK ratio 18: 46: 0) Remarks: The LC50 was obtained by graphical interpolation of mortality at different concentrations. Feeding rates Diammonium Phosphate ( DAP) CAS # 7783 28 0 22 decreased with increasing concentration ( LOEC = 300 mg/ L). Growth also decreased with increasing concentration. Metabolites of DAP contain ionized ammonium and phosphate, and these could disturb physiological activities of fish at high concentrations. This sublethal concentration is 40 times lower than that of urea. References: Palanichamy, S., Arunachalam, S., and Balasubramanian, M. P. 1985. Food consumption of Sarotherodon mossambicus ( Trewaves) exposed to sublethal concentration of diammonium phosphate. Hydrobiologia 128: 233 237.

( c) Type of test: Static [ X]; Semi static [ ]; Flow through [ X]; Opensystem [ X]; Closed system [ ] Species: Pimephales promelas ( Fathead minnows) Exposure period: 96 hour Results: LC50 ( DAP; pH 7.8) = 155 mg/ L LC50 ( Phos Check ® 202, 7 8 static) = 1320 µ l PC202/ L ( equivalent to 150 mg DAP/ L) Analytical monitoring: Yes [ X]; No [ ]; ? [ ] Method: Concentrations of PC202 used in both the flow through and static bioassays were 2500, 1877, 1400, 1050, and 800 µ l PC202/ L slurry. Each 20 L glass jar contained 15 L of solution and 10 fish. DAP toxicity was also measured directly in static experiments. GLP: Yes [ ] No [ ] ? [ X] Test substance: DAP and Phos Check ® 202 ( PC202) Remarks: The Phos Check ® 202 slurry contained 10.6% DAP diluted with water, plus thickeners. The flowthrough LC50 for PC202 was 1,022 µ l PC202/ L. The acute toxicity of PC202 is mainly due to the toxicity of the DAP content. References: Inman, R. C. 1974. Acute toxicity of Phos Check ® 202 and Diammonium Phosphate to Fathead Minnows. U. S. Air Force Environmental Health Laboratory, Kelly Air Force Base, TX. Report EHL( K) 74 31.

( d) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Opensystem [ X]; Closed system [ ] Species: Cirrhinus mrigala Exposure period: 96 hours Results: LC50 ( fry; 21 ° C) = 1,700 mg/ L LC50 ( fry; 26 ° C) = 1,610 mg/ L LC50 ( fry; 31 ° C) = 298 mg/ L LC50 ( fry; 36 ° C) = 115 mg/ L Diammonium Phosphate ( DAP) CAS # 7783 28 0 23 LC50 ( fingerlings; 21 ° C) = 1,875 mg/ L LC50 ( fingerlings; 26 ° C) = 1,665 mg/ L LC50 ( fingerlings; 31 ° C) = 970 mg/ L LC50 ( fingerlings; 36 ° C) = 655 mg/ L Analytical monitoring: Yes [ ]; No [ ]; ? [ X] Method: Bioassay tests were conducted on fry and fingerlings after methods described in APHA ( 1985). Tests were made in 10 L aquaria at pH 7.5. Each concentration was tested in four replicates accompanied by controls, with ten fry and four fingerlings per aquarium ( i. e., forty fry and sixteen fingerlings per concentration). GLP: Yes [ ] No [ ] ? [ X] Test substance: Diammonium phosphate (( NH4) 2HPO4), commercial grade Remarks: The toxicity of DAP to fish increased with increasing water temperature. In addition, in tests in which fish were exposed to both DAP and the pesticide simazine, the presence of DAP fertilizer reduced the toxicity of simazine. References: 1) Sarkar, S. K. 1997. Toxicity of simazine, diammonium phosphate and rock phosphate to fish, snail and worm at various water temperatures. Geobios 24: 142 145. 2) American Public Health Association ( APHA). 1985. Standard Methods for the Examination of Water and Wastewater. Washington, D. C.

4.2 ACUTE TOXICITY TO AQUATIC INVERTEBRATES A. Daphnia Remarks: No data available.

B. Other aquatic organisms ( a) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Opensystem [ X]; Closed system [ ] Species: Gammarus pseudolimnaeus ( amphipod) Exposure period: 96 hours Results: LC50 ( Phos Chek 202) = 52 mg/ L LC50 ( Phos Chek 259) = 40 mg/ L Analytical monitoring: Yes [ ]; No [ ]; ? [ X] Method: At least 10 amphipods per concentration were exposed for 96 hours to six concentrations of a commercial formulation containing 89% DAP plus thickening, coloring, and anti corrosion additives. Tests were conducted n reconstituted deionized water at a pH of Diammonium Phosphate ( DAP) CAS # 7783 28 0 24 7.2 7.5 and hardness of 40 50 mg/ L as CaCO3. Temperature was maintained at 18 ± 1oC. GLP: Yes [ ] No [ ] ? [ X] Test substance: Phos Chek 202 and Phos Chek 259 References: Johnson, W. W. and Finley, M. T. 1980. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. USDOI, Fish & Wildlife Service Resource Publication 137.

( b) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Opensystem [ X]; Closed system [ ] Species: Viviparus bengalensis ( snail) and Branchiura sowerbyi ( worm) Exposure period: 96 hours Results: LC50 ( V. bengalensis; 21 ° C) = 2,472 mg/ L LC50 ( V. bengalensis; 26 ° C) = 2,450 mg/ L LC50 ( V. bengalensis; 31 ° C) = 1,850 mg/ L LC50 ( V. bengalensis; 36 ° C) = 1,005 mg/ L LC50 ( B. sowerbyi; 21 ° C) = 2,455 mg/ L LC50 ( B. sowerbyi; 26 ° C) = 2,005 mg/ L LC50 ( B. sowerbyi; 31 ° C) = 1,740 mg/ L LC50 ( B. sowerbyi; 36 ° C) = 1,200 mg/ L Analytical monitoring: Yes [ ]; No [ ]; ? [ X] Method: Bioassay tests were conducted on snails and worms after methods described in APHA ( 1985). Tests were made in 500 mL glass beakers at pH 7.5. Each concentration was tested in four replicates accompanied by controls, with either six snails or ten worms per beaker ( i. e., 24 snails and 40 worms per concentration). GLP: Yes [ ] No [ ] ? [ X] Test substance: Diammonium phosphate (( NH4) 2HPO4), commercial grade Remarks: The toxicity of DAP to both species increased with increasing water temperature. In addition, in tests in which snails and worms were exposed to both DAP and the pesticide simazine, the presence of DAP fertilizer reduced the toxicity of simazine. References: 1) Sarkar, S. K. 1997. Toxicity of simazine, diammonium phosphate and rock phosphate to fish, snail and worm at various water temperatures. Geobios 24: 142 145. 2) American Public Health Association ( APHA). 1985. Standard Methods for the Examination of Water and Wastewater. Washington, D. C. Diammonium Phosphate ( DAP) CAS # 7783 28 0 25 4.3 TOXICITY TO AQUATIC PLANTS, e. g. algae Species: Selenastrum capricornutum Endpoint: Biomass [ X ]; Growth rate [ X ]; Other [ ] Exposure period: 72 hours Results: NOEC ( toxicity) = 97.1 mg DAP/ L NOEC ( stimulation) = 3.57 mg DAP/ L Analytical monitoring: Yes [ X ]; No [ ]; ? [ ] Method: OECD 201, 1984. Open system [ X ]; Closed system [ ] GLP: Yes [ X ] No [ ] ? [ ] Test substance: Diammonium phosphate ( 7783 28 0) Remarks: No adverse inhibitory effects were observed. There was some stimulation at 6.25 mg/ L and above. This was consistent with the known stimulatory effect of phosphate compounds. The reported NOEC reflects this stimulatory response and is not considered to be an adverse effect. All reported concentrations were calculated from the total phosphate measurements. References: Aufderheide, J. A. and Bussard, J. B. 2000. Toxicity of Diammonium Phosphate ( DAP) to the Unicellular Green Alga, Selenastrum capricornutum. ABC Study No. 46207.

4.4 TOXICITY TO BACTERIA Remarks: No data available.

4.5 CHRONIC TOXICITY TO AQUATIC ORGANISMS 4.5.1 CHRONIC TOXICITY TO FISH Remarks: No data available.

4.5.2 CHRONIC TOXICITY TO AQUATIC INVERTEBRATES Remarks: No data available.

4.6 TOXICITY TO TERRESTRIAL ORGANISMS 4.6.1 TOXICITY TO SOIL DWELLING ORGANISMS Remarks: No data available. Diammonium Phosphate ( DAP) CAS # 7783 28 0 26 4.6.2 TOXICITY TO TERRESTRIAL PLANTS Remarks: No data available.

4.6.3 TOXICITY TO OTHER NON MAMMALIAN TERRESTRIAL SPECIES ( INCLUDING AVIAN)

Remarks: No data available.

4.7 BIOLOGICAL EFFECTS MONITORING ( INCLUDING BIOMAGNIFICATION)

Remarks: No data available.

4.8 BIOTRANSFORMATION AND KINETICS Remarks: No data available.

4.9 ADDITIONAL REMARKS ( a) Type of test: Static [ ]; Semi static [ ]; Flow through [ X]; Other ( e. g. field test) [ ] Open system [ ]; Closed system [ ] Species: Clarias batrachus Exposure period: 144 h Results: See remarks. Analytical monitoring: Yes [ X]; No [ ]; ? [ ] Method: Healthy fish collected from the river Gomti of Lucknow ( India) were exposed to 0, 810, 860, 920, 970, 1010, or 1100 mg DAP/ L. The pH varied between 7.05 and 7.57 and the temperature varied between 23.1 and 25.1oC. Blood was collected and analyzed for hemoglobin, RBC count, Hct, and TLC. GLP: Yes [ ] No [ ] ? [ X] Test substance: Diammonium phosphate (( NH4) 2HPO4) Remarks: Hemoglobin content decreased at all concentrations. Hemoglobin was minimum at highest exposures, which proved lethal to fish. At all concentrations, the RBC count was lowest at the 144 h exposure. At higher concentrations the cell count decreased suddenly. The hematocrit content decreased over long durations, but seemed unaffected at lower concentrations and during shorter intervals. Similar results were seen with another fish species, Heteropneutes fossilis. Effects of DAP were more pronounced than urea. Diammonium Phosphate ( DAP) CAS # 7783 28 0 27 References: 1) Trivedi, S. P., Singh, P., Sethi, N. and Singh, R. K. 1990. Evaluations of hematotoxic effects of two commonly used fertilizers, diammonium phosphate and urea, on fish Clarias batrachus. Ecotoxicology and Environmental Safety. 19: 135 142. 2) Trivedi, S. P., Sethi, N., Singh, S. K. and Singh, P. 1989. Impact of fertilizer, diammonium phosphate, on haematological profile of teleost fish, Heteropneutes fossilis. Bio. Mem. 15: 166 174.

( b) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Other ( e. g. field test) [ ] Open system [ X]; Closed system [ ] Species: Clarias batrachus ( teleost) Exposure period: 144 hours Results: See remarks. Analytical monitoring: Yes [ ]; No [ ]; ? [ X] Method: Fish were collected from river Gomti of District Lucknow ( India) and were exposed to six concentrations of diammonium phosphate ranging from 810 to 1100 mg/ L. After 144 hours, fish were sacrificed and their liver, kidney, and muscle tissues examined. GLP: Yes [ ] No [ ] ? [ X] Test substance: Diammonium phosphate (( NH4) 2HPO4) Remarks: Peak elevations in 5' Nucleotidase levels were seen after 120 hours exposure at 860 mg/ L in liver and kidney and after 144 hours at 810 mg/ L in muscles. Peak inhibition was observed after 24 hours at 1010 mg/ L in liver and at 1100 mg/ L in kidney and muscle tissue. The authors suggest that diammonium phosphate may result in disturbances in the general metabolism of fish by altering the activity of 5' Nucleotidase. The significance of this biomarker of high dose exposure to actual toxicity at environmentally relevant doses is uncertain. References: Naqvi, T. S., Naqvi. M. S., and Singh, R. K. 1993. Effect of fertilizer diammonium phosphate on liver, kidney and muscle 5' nucleotidase activity of fresh water teleost fish Clarias batrachus. Biomedical and Environmental Sciences 6: 385 388.

( c) Type of test: Static [ X]; Semi static [ ]; Flow through [ ]; Other ( e. g. field test) [ ] Open system [ X]; Closed system [ ] Species: Clarias batrachus ( teleost) Endpoint: Length of fish [ ]; Weight of fish [ ]; Reproduction rate [ ]; Other [ X] Exposure period: 24 to 144 hours Results: See remarks. Analytical monitoring: Yes [ ]; No [ ]; ? [ X] Diammonium Phosphate ( DAP) CAS # 7783 28 0 28 Method: Healthy fish collected from the river Gomti at Lucknow ( India) were acclimatized for 96 hours. Aquaria were maintained at 28 ° C and pH 7.22. Fish were exposed for 24, 48, 72, 96, 120 or 144 hours to 810, 860, 920, 970, 1010, and 1100 mg/ L diammonium phosphate. Each treatment group consisted of ten fish. Blood was collected from the tail to determine levels of serum glutamate pyruvate transaminase. GLP: Yes [ ] No [ ] ? [ X] Test substance: Diammonium phosphate (( NH4) 2HPO4). Remarks: The enzymatic activity increased above control in the initial periods of exposures at all concentrations, except at the highest concentration, which proved lethal and reduced activity. While the authors conclude that DAP causes toxicity in the liver of C. batrachus, this endpoint really is a biomarker for exposure. The true toxicological significance of this high dose response relative to environmentally significant doses and endpoints is uncertain. References: Singh, R., Singh, R. K., and Pande, P. N. 1995. Biochemical toxicity of fertilizer di ammonium phosphate to fish Clarias batrachus. Uttar Pradesh J. Zool. 15( 2): 144 148.

5. TOXICITY 5.1 ACUTE TOXICITY 5.1.1 ACUTE ORAL TOXICITY Type: LD0 [ ]; LD100 [ ]; LD50 [ X ]; LDL0 [ ]; Other [ ] Species/ strain: Sprague Dawley rat, albino Value: > 2,000 mg/ kg bw Method: OECD 425, " Up and Down Protocol" An initial dose of two thousand milligrams of the test substance per kilogram of bodyweight was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal a second female received the same dose level. Following the completion of dosing and 100% survival in a total of three females, a group of three males was tested ( simultaneously) at the above dose level. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Bodyweights were recorded prior to administration and again on Days 7 and 14 ( termination) after dosing. Necropsies were performed on all animals at terminal sacrifice. Diammonium Phosphate ( DAP) CAS # 7783 28 0 29 GLP: Yes [ X ] No [ ] ? [ ] Test substance: Diammonium phosphate ( dark brown granules) Remarks: Prior to use, the test substance was ground in a coffee mill and administered by gavage as a 70% w/ w suspension in distilled water ( preliminary solubility testing indicated that suspension in excess of 70% were too viscous to be administered properly). All animals survived, gained weight and appeared active and healthy throughout the study period. No signs of toxicity were observed. References: Merkel, D. J. 2000. Acute oral toxicity: Up and down procedure in rats limit test. Product Safety Labs study number 9733.

5.1.2 ACUTE INHALATION TOXICITY Remarks: No data available.

5.1.3 ACUTE DERMAL TOXICITY Type: LD0 [ ]; LD100 [ ]; LD50 [ X ]; LDL0 [ ]; Other [ ] Species/ strain: Sprague Dawley rat, albino Value: > 5,000 mg/ kg bw Method: OECD 402, 1987. Limit test ( 5 males/ 5 females). DAP was applied to the shaved intact skin on the back of each rat and covered with gauze pads. After 24 hours the pads were removed and the test areas gently wiped with water. GLP: Yes [ X ] No [ ] ? [ ] Test substance: Diammonium phosphate ( dark brown granules) Remarks: Prior to application, the test substance was ground in a coffee mill and moistened to achieve a dry paste by preparing a 85% w/ w mixture. All animals survived, gained weight and appeared active and healthy throughout the test. No signs of toxicity were observed. References: Merkel, D. J. 2000. Acute dermal toxicity study in ratslimit test. Product Safety Labs study number 9736.

5.1.4 ACUTE TOXICITY BY OTHER ROUTES OF ADMINISTRATION Remarks: No data available. Diammonium Phosphate ( DAP) CAS # 7783 28 0 30 5.2 CORROSIVENESS/ IRRITATION 5.2.1 SKIN IRRITATION/ CORROSION Remarks: Irritant References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

5.2.2 EYE IRRITATION/ CORROSION Remarks: Irritant References: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

5.3 SKIN SENSITIZATION Remarks: No data available.

5.4 REPEATED DOSE TOXICITY Species: Rat Sex/ strain: Male/ Female Crl: CD( SD) IGS BR Route of administration: Gavage Exposure period: Animals were divided between two subgroups ( toxicity and reproductive subgroups). The exposure period for the toxicity subgroup was 35 days, while the exposure period for the reproductive subgroup was at most 28 days among male and 53 days among females. Frequency of treatment: Daily Doses: 0, 250, 750, and 1,500 mg/ kg/ day ( doses were selected based on parameters assessed in a range finding study at concentrations up to 1,000 mg/ kg/ day) NOAEL: 250 mg/ kg/ day ( general toxicity) 1,500 mg/ kg/ day ( reproduction/ developmental toxicity) LOAEL: 500 mg/ kg/ day ( general toxicity) > 1,500 mg/ kg/ day ( reproduction/ developmental toxicity) GLP: Yes Method: Toxicity subgroup: Animals comprising the toxicity subgroup ( 5 males and 5 females per dose group) were administered Diammonium Phosphate ( DAP) for 5 weeks ( 7 days/ week) via gavage administration. Among Diammonium Phosphate ( DAP) CAS # 7783 28 0 31 toxicity subgroup animals, functional observations ( sensory reactivity, grip strength, motor activity) and bleeds for hematology and blood chemistry were conducted during week 5 of treatment. Organ weights were recorded at termination during Week 6 and major organs and tissues ( and any other abnormalities observed at necropsy) were processed for microscopic examination. Reproductive subgroup: Animals comprising the reproductive subgroup ( 5 males and 10 females) were administered DAP for a period encompassing approximately 53 continuous days via oral gavage: 14 days of initial treatment, plus a maximum of 14 days of cohabitation to ensure mating, and among females, at least 25 days to litter and rear their young until day 4 of age. Histology for reproductive subgroup animals was restricted to retained reproductive organs ( and any other abnormalities observed at necropsy). Result: Toxicity subgroup: There were no treatment related deaths and no signs of overt clinical toxicity. Bodyweight gain and food consumption appeared to be suppressed among males at 1,500 mg/ kg/ day. Bodyweight gain for reproductive subgroup females receiving 1,500 mg/ kg/ day was reduced during the first week of gestation, after which they returned to levels comparable to the controls for the remainder of the study. The only treatment related change evident in haematology was a reduction in activated partial thromboplastin time for males at 750 or 1,500 mg/ kg/ day. There was a slightly greater variability in blood chemistry parameters, and the following were blood chemistry changes for males that may represent an effect of treatment: a non dosage dependant elevation of alkaline phosphatase levels at 750 and 1,500 mg/ kg/ day; reduced glucose and phosphorous levels at 1,500 mg/ kg/ day; a dosage dependant reduction in total protein at 750 and 1,500 mg/ kg/ day with a slightly elevated albumin/ globulin ratio at the high dose. Changes in females were limited to a decrease in phosphorous levels and a non significant increase in alkaline phosphatase levels at 1,500 mg/ kg/ day. Reddening of the extremities during the first week of dosing was observed in all doses, including 250 mg/ kg/ day but reduced as the treatment period progressed. Histological examination of the stomachs revealed some submucosal inflammation at all doses, but this change was not dose dependent and was not statistically significant at the low dose. Reproductive subgroup: There were no treatment related deaths and no signs of overt clinical toxicity. Mating performance and fertility were unaffected by treatment, Diammonium Phosphate ( DAP) CAS # 7783 28 0 32 and parental treatment had no apparent effect on the offspring to day 4 of age. Test substance: Diammonium Phosphate ( DAP) Reference: Huntingdon Life Sciences Ltd. 2002. DAP: 4 Week General Toxicity and Reproductive/ Developmental Toxicity Screening Test. Study Number WBG 001/ 022948.

5.5 GENETIC TOXICITY IN VITRO A. Bacterial Test Type: Bacterial reverse mutation assay System of testing: Species/ strain: Salmonella typhimurium TA 98, TA100, TA1535, TA1537 and E. coli WP2 uvrA Concentration: 50, 150, 500, 1,500, and 5,000 µ g/ plate Metabolic activation: With [ ]; Without [ ]; With and Without [ X]; Results: Cytotoxicity conc: With metabolic activation: None observed Without metabolic activation: None observed Precipitation conc: 5,000 µ g/ plate Genotoxic effects: + ?  With metabolic activation: [ ] [ ] [ X] Without metabolic activation: [ ] [ ] [ X] Method: OECD Guideline 471 ( Ninth Addendum; February 1998) GLP: Yes [ X] No [ ] ? [ ] Test substance: Diammonium phosphate ( DAP), purity: 100% Remarks: Concentrations from 10 to 50 mg/ mL of the test article in water were workable suspensions. References: Wagner, V. O. and Klug, M. L. 2001. Bacterial Reverse Mutation Assay: Diammonium Phosphate ( DAP). BioReliance. Sponsor Project Number TFI002 AMES.

B. Non bacterial in vitro test Type: Mammalian chromosome aberration test System of testing: Species/ strain: Chinese hamster ovaries Concentration: 185 to 1,480 µ g/ mL Metabolic activation: With [ ]; Without [ ]; With and Without [ X]; Results: Cytotoxicity conc: With metabolic activation: None Without metabolic activation: None Precipitation conc: None Genotoxic effects: + ?  With metabolic activation: [ ] [ ] [ X] Without metabolic activation: [ ] [ ] [ X] Method: OECD Guideline 473 ( Ninth Addendum; February 1998) Diammonium Phosphate ( DAP) CAS # 7783 28 0 33 GLP: Yes [ X] No [ ] ? [ ] Test substance: Diammonium phosphate ( DAP), purity: 100% References: Gudi, R. and Brown, C. 2001. In Vitro Mammalian Chromosome Aberration Test: Diammonium Phosphate ( DAP). BioReliance. Sponsor Project Number TFI002 CHO.

5.6 GENETIC TOXICITY IN VIVO Remarks: No data available.

5.7 CARCINOGENICITY Remarks: No data available.

5.8 TOXICITY TO REPRODUCTION Remarks: See summary in Section 5.4 5.9 DEVELOPMENTAL TOXICITY/ TERATOGENICITY Remarks: See summary in Section 5.4 5.10 OTHER RELEVANT INFORMATION Remarks: Toxicity of diammonium phosphate is considered to be " low to moderate". It is an eye, respiratory and skin irritant, and appears to be stronger in these respects than monoammonium phosphate. No evidence was found for chronic effects distinct from acute toxicity. A number of instances of livestock poisoning have been reported due to accidents in the handling of feeds and fertilizer fortified with ammonium salts, including DAP. Reference: European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition . Diammonium Phosphate ( DAP) CAS # 7783 28 0 34 5.11 EXPERIENCE WITH HUMAN EXPOSURE ( a) Remarks: DAP is affirmed as " generally recognized as safe" ( GRAS) for use as a food additive for both human food and ruminant feed according to prescribed conditions. Reference: 21 CFR 582.1141 as cited in Hazardous Substances Data Bank ( HSDB).

( b) Results: Urea plant workers showed significant reduction in Peak Expiratory Flow Rate per minute ( PEFR/ min), but not Forced Vital Capacity ( FVC) and Forced Expiratory Volume ( FEV), when compared to the controls. Ammonia plant workers showed a decrease in FEV, and FEFR/ min, but not FVC. DAP plant workers showed a significant reduction in all three parameters. All three fertilizer chemicals appear to affect larger airways immediately. According to the authors, the volatility of ammonia and DAP enable them to enter the smaller bronchioles and cause hypersensitive reaction leading to bronchospasm. These changes apparently occur slowly and continuously. These fertilizers also affect the pulmonary alveoli only after longer exposure and cause restrictive types of lung disorders. Of the three materials, DAP has the greatest affect, followed by ammonia, and urea has the least affect. Remarks: Lung function tests were performed on 30 diammonium phosphate, 31 ammonia, and 30 urea plant workers at the Mangalore Fertilizer Chemical Plant. A group of 68 people served as controls. All tests were performed in the standing position, exhaling into a spirometer. Each test was repeated three times and the highest reading was taken for calculation. Subjects were split into two groups of up to 10 years of exposure and more than 10 years of exposure. Reference: Bhat, M. R. and Ramaswamy, C. 1993. Effect of ammonia, urea and diammonium phosphate ( DAP) on lung functions in fertilizer plant workers. Indian J. Physiol. Pharmacol. 37: 222 224. Diammonium Phosphate ( DAP) CAS # 7783 28 0 35 6. REFERENCES 21 CFR 582.1141 as cited in Hazardous Substances Data Bank ( HSDB).

American Public Health Association ( APHA). 1985. Standard Methods for the Examination of Water and Wastewater. Washington, D. C.

Aufderheide, J. A. and Bussard, J. B. 2000. Toxicity of Diammonium Phosphate ( DAP) to the Unicellular Green Alga, Selenastrum Capricornutum. ABC Study No. 46207.

Bhat, M. R. and Ramaswamy, C. 1993. Effect of ammonia, urea and diammonium phosphate ( DAP) on lung functions in fertilizer plant workers. Indian J. Physiol. Pharmacol. 37: 222 224.

Budavari, S. 1996. The Merck Index. Whitehouse Station: Merck Research Laboratories.

European Commission 2000. Diammonium Hydrogenorthophosphate. International Uniform Chemical Information Database. Year 2000 CD   ROM edition.

Gudi, R. and Brown, C. 2001. In Vitro Mammalian Chromosome Aberration Test: Diammonium Phosphate ( DAP). BioReliance. Sponsor Project Number TFI002 CHO.

Hazardous Substances Data Bank ( HSDB). 1999. Diammonium phosphate. National Library of Medicine, Bethesda, MD.

Huntingdon Life Sciences Ltd. 2002. DAP: 4 Week General Toxicity and Reproductive/ Developmental Toxicity Screening Test. Study Number WBG 001/ 022948.

Inman, R. C. 1974. Acute toxicity of Phos Check ® 202 and Diammonium Phosphate to Fathead Minnows. U. S. Air Force Environmental Health Laboratory, Kelly Air Force Base, TX. Report EHL( K) 74 31.

IPCS. 1993. International Chemical Safety Cards No. 0217. Ammonium Phosphate Dibasic.

Johnson, W. W. and Finley, M. T. 1980. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. USDOI, Fish & Wildlife Service Resource Publication 137.

Johnson, W. W. and Sanders, H. O. 1977. Chemical forest fire retardants: Acute toxicity to five freshwater fishes and a scud. Technical Papers of the U. S. Fish and Wildlife Service.

Lewis, Jr., R. J. 1992. Sax's Dangerous Properties of Industrial Materials. 8th ed. Vol. II. New York: Van Nostrand Reinhold. Diammonium Phosphate ( DAP) CAS # 7783 28 0 36 Lide, D. R. 1992. CRC Handbook of Chemistry and Physics. Boston: CRC Press.

Merkel, D. J. 2000. Acute dermal toxicity study in rats limit test. Product Safety Labs study number 9736.

Merkel, D. J. 2000. Acute oral toxicity: Up and down procedure in rats limit test. Product Safety Labs study number 9733.

Naqvi, T. S., Naqvi. M. S., and Singh, R. K. 1993. Effect of fertilizer diammonium phosphate on liver, kidney and muscle 5' nucleotidase activity of fresh water teleost fish Clarias batrachus. Biomedical and Environmental Sciences 6: 385 388.

Palanichamy, S., Arunachalam, S., and Balasubramanian, M. P. 1985. Food consumption of Sarotherodon mossambicus ( Trewaves) exposed to sublethal concentration of diammonium phosphate. Hydrobiologia 128: 233 237.

Sarkar, S. K. 1997. Toxicity of simazine, diammonium phosphate and rock phosphate to fish, snail and worm at various water temperatures. Geobios 24: 142 145.

Singh, R., Singh, R. K., and Pande, P. N. 1995. Biochemical toxicity of fertilizer diammonium phosphate to fish Clarias batrachus. Uttar Pradesh J. Zool. 15( 2): 144 148.

Trivedi, S. P., Sethi, N., Singh, S. K. and Singh, P. 1989. Impact of fertilizer, diammonium phosphate, on haematological profile of teleost fish, Heteropneutes fossilis. Bio. Mem. 15: 166 174.

Trivedi, S. P., Singh, P., Sethi, N. and Singh, R. K. 1990. Evaluations of hematotoxic effects of two commonly used fertilizers, diammonium phosphate and urea, on fish Clarias batrachus. Ecotoxicology and Environmental Safety. 19: 135 142.

United Nations Industrial Development Organization ( UNIDO) and International Fertilizer Development Center ( IFDC). 1998. Fertilizer Manual. Kluwer Academic Publishers, The Netherlands.

USEPA. 2000. EPISUITE Estimation Program V. 3.10. US Environmental Protection Agency.

Wagner, V. O. and Klug, M. L. 2001. Bacterial Reverse Mutation Assay: Diammonium Phosphate ( DAP). BioReliance. Sponsor Project Number TFI002 AMES. Diammonium Phosphate ( DAP) CAS # 7783 28 0 APPENDIX A   SIDS Data Availability Summary Diammonium Phosphate ( DAP) CAS # 7783 28 0 Explanation of Appendix A Appendix A is a SIDS Data Summary table that provides an overview of availability and quality of the data used in this Health and Environmental Safety Data Summary for Diammonium Phosphate ( DAP). Y ( Yes) and N ( No) designations indicate whether data are available that meet the criteria for each column. The columns are described as:

Information: Data exist that were useful for describing the data element. These data may be from standard laboratory tests or from generally recognized published sources or professional experience.

OECD Study: The data were developed using standard OECD or essentially similar ( e. g., EPA harmonized protocols) guidelines.

GLP: The data were developed under standard Good Laboratory Practice provisions. These generally represent the highest quality data.

Other Study: Studies were conducted that could not be definitively identified as following OECD or GLP protocols. These studies were included when they were determined to be of adequate quality and provided relevant information to the characterization of the compound.

Estimation Method: In some cases, data may be estimated using established structure activity relationships. These methods are common for physical chemical parameters such as octanolwater partition coefficients and water solubility.

Acceptable: This column indicates whether the data are deemed acceptable by standard acceptability criteria and professional judgment. Only the data meeting adequacy standards are included in this summary document.

SIDS Testing Recommended: This column indicates whether additional testing is recommended based on an evaluation of the available data summarized in this document. It is generally not necessary to fill all of the apparent data gaps in order to adequately characterize the inherent hazard of chemicals. Information from other data elements and from other chemicals in the category, along with professional judgment, are useful in the final determination of the need for further testing. Diammonium Phosphate ( DAP) CAS # 7783 28 0 SIDS DATA AVAILABILITY SUMMARY DATE: January 27, 2003 Diammonium Phosphate ( DAP) CAS No: 1336 21 6 Information OECD Study GLP Other Study Estimated Method Acceptable SIDS Testing Recommended STUDY Y/ N Y/ N Y/ N Y/ N Y/ N Y/ N Y/ N PHYSICAL CHEMICAL DATA 2.1 2.2 2.3 2.4 2.5 2.6 2.8 2.9 2.10 2.11 2.12 Melting Point Boiling Point Density Vapor Pressure Partition Coefficient Water Solubility pH and pKa Values Autoflammability Flammability Explosive Properties Oxidizing Properties Oxidation: Reduction Potential Y Y Y Y N Y Y Y Y Y Y N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N Y Y Y Y  Y Y Y Y Y Y  N N N N N N N N N N N N OTHER P/ C STUDIES RECEIVED Y N N N N Y N ENVIRONMENTAL FATE and PATHWAY 3.1.1 3.1.2 3.1.3 3.2 3.3 3.5 3.7 Photodegradation Stability in Water Stability in Soil Monitoring Data Transport and Distribution Biodegradation Bioaccumulation N Y Y N Y Y Y N N N N N N N N N N N N N N N N N N N N N N N N N N Y N  Y Y  Y Y Y N N N N N N N OTHER ENV FATE STUDIES RECEIVED N N N N N  N ECOTOXICITY 4.1 4.2A 4.2B 4.3 4.5.1 4.5.2 4.6.1 4.6.2 4.6.3 Acute Toxicity to Fish Acute Toxicity to Daphnia Acute Toxicity to Other Aquatic Organisms Toxicity to Algae Chronic Toxicity to Fish Chronic Toxicity to Daphnia Toxicity to Soil Dwelling Organisms Toxicity to Terrestrial Plants Toxicity to Birds Y N Y Y N N N N N N N N Y N N N N N N N N Y N N N N N Y N Y N N N N N N N N N N N N N N N Y  Y Y      N N N N N N N N N OTHER ECOTOXICITY STUDIES RECEIVED Y N N Y N Y N TOXICITY 5.1.1 5.1.2 5.1.3 5.2 5.4 5.5 5.6 5.8 5.9 5.11 Acute Oral Acute Inhalation Acute Dermal Skin/ Eye Irritation Repeated Dose Genetic Toxicity in vitro . Gene mutation . Chromosomal aberration Genetic Toxicity in vivo Reproduction Toxicity Development/ Teratogenicity Human Experience Y N Y N Y Y Y N Y Y Y Y N Y N Y Y Y N Y Y N Y N Y N Y Y Y N Y Y N N N N N N N N N N N Y N N N N N N N N N N N Y  Y

Y Y  Y Y Y N N N N N N N N N N N OTHER TOXICITY STUDIES RECEIVED Y N N Y N Y N Diammonium Phosphate ( DAP) CAS # 7783 28 0 Appendix B   SIDS Data Summaries for the Phosphate Compounds Category: Diammonium Phosphate, Liquid Polyphosphate, Monoammonium Phosphate, and Super Phosphates SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS PHYSICAL CHEMICAL DATA 2.1 Melting Point 155 ° C 190 ° C 2.2 Boiling Point Decomposes Decomposes 2.3 Density 0.93 1.619 g/ mL at 20oC 1.43 g/ mL at 60oC 1.83 g/ mL at 25oC 2.4 Vapor Pressure < 100 Pa at 20 ° C < 100 Pa at 20 ° C 2.5 Octanol/ Water Partition Coefficient 2.6A Water Solubility 588 g/ L at 20 ° C Miscible 328 g/ L at 20 ° C 2.6B pH and pKa values ~ 8 6.5 7 4.2 in 0.2M aqueous solution 2.7 Flash Point Not applicable Not flammable Not applicable 2.8 Auto Flammability Not flammable Not applicable Not flammable 2.9 Flammability Not flammable Not flammable Not flammable 2.10 Explosive Properties Not explosive Not explosive Not explosive 2.11 Oxidizing Properties Not an oxidizer Not an oxidizer 2.12 Oxidation:

Reduction Potential 2.13A Additional Data See text SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS ENVIRONMENTAL FATE and PATHWAY 3.1.1 Photodegradation 3.1.2 Stability in Water Stable Stable Stable 3.1.3 Stability in Soil Stable Behave as salts Stable 3.3.2 Distribution Calculated,

Fugacity Level III 6.5 x 10 15% to air 45.3% to water 54.6% to soil 0.0755% to sediment Calculated,

Fugacity Level III 3.98 x 10 12% to air 45.3% to water 54.6% to soil 0.0755% to sediment 3.5 Biodegradation Phosphorus cycles is well understood Phosphorus cycles is well understood Phosphorus cycles is well understood 3.7 Bioaccumulation Does not bioaccumulate Does not bioaccumulate Does not bioaccumulate SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS ECOTOXICITY 4.1 Acute toxicity to Fish Coho salmon, Chinook salmon, Rainbow trout, Bluegill, Largemout h bass, Tilapia, Fathead minnow 96 hrs LC50 = 90 1,875 mg/ L Oncorhync hus mykiss 96 hrs LC50 = > 101 mg/ L Oncorhync hus mykiss 96 hrs LC50 = > 85.9 mg/ L 4.2 Acute Toxicity to Aquatic Invertebrates Daphnia magna Amphipod Snail, Worm 96 hrs 96 hrs LC50 = 40 52 mg/ L LC50 = 1,005

2,472 mg/ L 4.3 Toxicity to Aquatic Plants ( Algae) Selenastrum capricornutum 72 hrs NOEC ( stimulation) =

3.57 mg DAP/ L NOEC ( toxicity)

= 97.1 mg DAP/ L 4.4 Toxicity to Bacteria 4.5.1 Chronic Toxicity to Fish 4.5.2 Chronic Toxicity to Aquatic Invertebrates 4.6.1 Toxicity to Soil Dwelling Organisms SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS 4.6.2 Toxicity to Terrestrial Plants 4.6.3 Toxicity to Other Non Mammalian Terrestrial Species SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS TOXICITY 5.1.1 Acute Oral Toxicity Rat OECD 425 LD50 > 2,000 mg/ kg bw Rat OECD 425 LD50 > 2,000 mg/ kg bw Rat OECD 425 LD50 > 2000 mg/ kg bw 5.1.2 Acute Inhalation 5.1.3 Acute Dermal Toxicity Rat OECD 402 LD50 > 5000 mg/ kg bw Rat OECD 402 LD50 > 5,000 mg/ kg bw Rat OECD 402 LD50 > 5000 mg/ kg bw 5.1.4 Acute Toxicity,

Other Routes 5.2.1 Skin Irritation/

Corrosion Irritant Mild irritant 5.2.2 Eye Irritation/

Corrosion Irritant Mild irritant 5.3 Skin Sensitization 5.4 Repeated Dose Rat OECD 422 NOAEL = 250 mg/ kg/ day 5.5 Genetic Toxicity in vitro . Gene mutation Salmonella typhimurium Bacterial reverse mutation assay ( OECD 471) Negative . Chromosomal aberration Chinese hamster ovaries Chromosome aberration test ( OECD 473) Negative 5.6 Genetic Toxicity in vivo 5.7 Carcinogenicity 5.8 Toxicity to Reproduction Rat OECD 422 NOAEL = 1500 mg/ kg/ day 5.9 Development Toxicity/ Teratogenicity Rat OECD 422 NOAEL = 1500 mg/ kg/ day 5.10 Metabolism and Toxicokinetics See text See text 5.11 Human Experience See text See text See text SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Diammonium Phosphate Liquid Polyphosphate Monoammonium Phosphate DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS 1.8 Occupational Exposure Limits TLV as inert dust 15 mg/ m3 No TLV established TLV as inert dust 15 mg/ m3 SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS PHYSICAL CHEMICAL DATA 2.1 Melting Point 110 ° C 2.2 Boiling Point 2.3 Density 1,035 kg/ m3 2.4 Vapor Pressure 2.5 Octanol/ Water Partition Coefficient 2.6A Water Solubility 18 g/ L at 20 ° C 2.6B pH and pKa values 2.8 2.9 in 10%

water suspension 2.7 Flash Point Not applicable 2.8 Auto Flammability 2.9 Flammability 2.10 Explosive Properties 2.11 Oxidizing Properties 2.12 Oxidation:

Reduction Potential 2.13A Additional Data SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS ENVIRONMENTAL FATE and PATHWAY 3.1.1 Photodegradation 3.1.2 Stability in Water 3.1.3 Stability in Soil Stable 3.3.2 Distribution Calculated,

Fugacity Level III 1x10 6% to air 49.8% to water 50.1% to soil 0.092% to sediment 3.5 Biodegradation Biodegradable 3.7 Bioaccumulation SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS ECOTOXICITY 4.1 Acute toxicity to Fish Labeo rohita, Catla catla, Cirrhinus mrigala, Cyprinus carpio, Tilapia mossambica 96 hrs LC50 = 1,560

5,900 ppm 4.2A Acute Toxicity to Aquatic Invertebrates Daphnia carinata LC50 = 1,790

1,825 mg/ L 4.2B Acute Toxicity to Other Aquatic Organisms Moina micrura,

Cyclops viridis 72 hrs LC50 = 1,625

2,305 ppm Branchiura sowerbyi, Planorbis exustus, Lymnaea leuteola, Viviparus bengalensis,

Chironomus sp 96 hrs LC50 = 1,133

5,005 ppm 4.3 Toxicity to Aquatic Plants ( Algae) Selenastrum capricornutum OECD 201 NOEC ( toxicity) =

87.6 mg/ L NOEC ( stimulation) =

21.6 mg/ L 4.4 Toxicity to Bacteria SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS 4.5.1 Chronic Toxicity to Fish 4.5.2 Chronic Toxicity to Aquatic Invertebrates 4.6.1 Toxicity to Soil Dwelling Aquatic Invertebrates 4.6.2 Toxicity to Terrestrial Plants See text 4.6.3 Toxicity to Other Non Mammalian Terrestrial Species SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS TOXICITY 5.1.1 Acute Oral Toxicity Sheep LD50 = 5,000

6,000 mg/ kg bw 5.1.2 Acute Inhalation 5.1.3 Acute Dermal Toxicity 5.1.4 Acute Toxicity,

Other Routes 5.2.1 Skin Irritation/

Corrosion Mild irritant 5.2.2 Eye Irritation/

Corrosion Mild irritant 5.3 Skin Sensitization 5.4 Repeated Dose Rat OECD 422 NOAEL = 750 mg/ kg/ day 5.5 Genetic Toxicity in vitro . Gene mutation Salmonella typhimurium OECD 471 Negative . Chromosomal aberration Chinese hamster ovaries OECD 473 Negative 5.6 Genetic Toxicity in vivo Mice Chromosome aberration Clastogenic,

possibly mutagenic 5.7 Carcinogenicity 5.8 Toxicity to Reproduction Rat OECD 422 NOAEL = 750 mg/ kg/ day 5.9 Development Toxicity/ Teratogenicity Rat OECD 422 NOAEL = 750 mg/ kg/ day SIDS DATA SUMMARIES FOR THE PHOSPHATE CATEGORY Date: January 27, 2003 Diammonium Phosphate ( DAP)

CAS # 7783 28 0 Super Phosphates DATA ELEMENTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS SPECIES PROTOCOL RESULTS 5.10 Metabolism and Toxicokinetics See text 5.11 Human Experience See text 1.8 Occupational Exposure Limits TLV as inert dust 15 mg/ m3


[Federal Register Volume 84, Number 52 (Monday, March 18, 2019)]
[Notices]
[Pages 9856-9858]
[FR Doc No: 2019-04947]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-85293; File No. SR-BOX-2019-05]

Self-Regulatory Organizations; BOX Exchange LLC; Notice of Filing
and Immediate Effectiveness of a Proposed Rule Change To Amend the BOX
Fee Schedule

March 12, 2019.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act''),\1\ and Rule 19b-4 thereunder,\2\ notice is hereby given that
on February 28, 2019, BOX Exchange LLC (``Exchange'') filed with the
Securities and Exchange Commission (``Commission'') the proposed rule
change as described in Items I and II below, which Items have been
prepared by the Exchange. The Commission is publishing this notice to
solicit comments on the proposed rule change from interested persons.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
---------------------------------------------------------------------------

I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    The Exchange proposes to amend to BOX Fee Schedule. The text of the
proposed rule change is available from the principal office of the
Exchange, at the Commission's Public Reference Room and also on the
Exchange's internet website at http://boxoptions.com.

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, the self-regulatory organization
included statements concerning the purpose of, and basis for, the
proposed rule change and discussed any comments it received on the
proposed rule change. The text of these statements may be examined at
the places specified in Item IV below. The self-regulatory organization
has prepared summaries, set forth in Sections A, B, and C below, of the
most significant aspects of such statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

1. Purpose
    The Exchange proposes to add Section VIII.B. (Fee Disputes) to the
BOX Fee Schedule. Specifically, the Exchange proposes that all fee
disputes concerning fees which are billed by the Exchange must be
submitted to the Exchange in writing and must be accompanied by
supporting documentation. All fee disputes must be submitted no later
than sixty (60) calendar days after receipt of billing invoice. The
Exchange notes that similar language exists at other options exchanges
in the industry.\3\
---------------------------------------------------------------------------

    \3\ See Nasdaq ISE, LLC (``ISE'') Options 7 Pricing Schedule
Section 1(b). See also Miami International Securities Exchange LLC
(``MIAX'') Fee Schedule cover page.

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    The Exchange provides Participants with both daily and monthly fee
reports and thus believes Participants should be aware of any potential
billing errors within sixty calendar days of receiving an invoice.
Requiring that Participants dispute an invoice within this time period
will encourage them to promptly review their invoices so that any
disputed charges can be addressed in a timely manner while the
information and data underlying those charges (e.g. applicable fees and
order information) is still easily and readily available. This practice
will avoid issues that may arise when Participants do not dispute an
invoice in a timely manner, and will conserve Exchange resources that
would have to be expended to resolve untimely billing disputes. The
Exchange notes that this type of provision is common among other
exchanges, which require that Participants dispute invoices within
sixty days.\4\
---------------------------------------------------------------------------

    \4\ Id.
---------------------------------------------------------------------------

    The sixty days would first apply to invoices related to
transactional billing in March 2019 and would apply thereafter. The
Exchange proposes to apply the billing policy to all charges reflected
in the BOX Fee Schedule.
2. Statutory Basis
    The Exchange believes that the proposal is consistent with the
requirements of Section 6(b) of the Act,\5\ in general, and Section
6(b)(5) of the Act,\6\ in particular, in that it is designed to promote
just and equitable principles of trade, remove impediments to and
perfect the mechanism of a free and open market and a national market
system, and, in general protect investors and the public interest, by
providing a uniform practice for disputing fees.
---------------------------------------------------------------------------

    \5\ 15 U.S.C. 78f(b).
    \6\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

    The Exchange believes the requirement that all billing disputes
must be submitted, in writing, and with supporting documentation,
within sixty calendar days from receipt of the invoice is reasonable
and in the public interest because the Exchange provides ample tools to
properly and swiftly monitor and account for various charges incurred
in a given month. Specifically, the Exchange sends a monthly PDF
invoice to all billing contacts outlining the charges, as well as daily
and monthly transaction details to assist with monitoring trade-related
charges. Moreover, the proposed fee dispute language, which will lower
the Exchange's administrative burden, is substantially similar to
billing dispute language at other options exchanges.\7\ Also, the
Exchange's administrative costs would be lowered as a result of this
policy because staff resources would not be diverted to review untimely
requests regarding billing.
---------------------------------------------------------------------------

    \7\ See supra note 3.
---------------------------------------------------------------------------

B. Self-Regulatory Organization's Statement on Burden on Competition

    The Exchange notes note believe that the proposed change will
impose any burden on competition that is not necessary or appropriate
in furtherance of the purposes of the Act. The billing policy would
apply uniformly to all BOX Participants. As discussed herein, the
policy is similar to policies in place by other options exchanges.\8\
---------------------------------------------------------------------------

    \8\ Id.
---------------------------------------------------------------------------

    Further, this proposal would provide a cost savings to the Exchange
in that it would alleviate processes related to the untimely review of
billing disputes which divert staff resources away from the Exchange's
regulatory and business purposes.
    As such, the Exchange does not believe that the proposed rule
change will impose any burden on competition not necessary or
appropriate in furtherance of the purposes of the Act.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants, or Others

    The Exchange has neither solicited nor received comments on the
proposed rule change.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    Because the foregoing proposed rule change does not: (i)
Significantly affect the protection of investors or the public
interest; (ii) impose any significant burden on competition; and (iii)
become operative for 30 days after the date of the filing, or such
shorter time as the Commission may designate, it has become effective
pursuant to 19(b)(3)(A) of the Act \9\ and Rule 19b-4(f)(6) \10\
thereunder.
---------------------------------------------------------------------------

    \9\ 15 U.S.C. 78s(b)(3)(A).
    \10\ 17 CFR 240.19b-4(f)(6). In addition, Rule 19b-4(f)(6)
requires a self-regulatory organization to give the Commission
written notice of its intent to file the proposed rule change at
least five business days prior to the date of filing of the proposed
rule change, or such shorter time as designated by the Commission.
The Exchange has satisfied this requirement.
---------------------------------------------------------------------------

    At any time within 60 days of the filing of the proposed rule
change, the Commission summarily may temporarily suspend such rule
change if it appears to the Commission that such action is: (i)
Necessary or appropriate in the public interest; (ii) for the
protection of investors; or (iii) otherwise in furtherance of the
purposes of the Act. If the Commission takes such action, the
Commission shall institute proceedings to determine whether the
proposed rule should be approved or disapproved.

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File Number SR-BOX-2019-05 on the subject line.

Paper Comments

     Send paper comments in triplicate to Secretary, Securities
and Exchange Commission, 100 F Street NE, Washington, DC 20549-1090.

All submissions should refer to File Number SR-BOX-2019-05. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's internet website (http://www.sec.gov/rules/sro.shtml).
Copies of the submission, all subsequent amendments, all written
statements with respect to the proposed rule change that are filed with
the Commission, and all written communications relating to the proposed
rule change between the Commission and any person, other than those
that may be withheld from the public in accordance with the provisions
of 5 U.S.C. 552, will be available for website viewing and printing in
the Commission's Public Reference Room, 100 F Street NE, Washington, DC
20549, on official business days between the hours of 10:00 a.m. and
3:00 p.m. Copies of the filing also will be available for inspection
and copying at the principal office of the Exchange. All comments
received will be posted without change. Persons submitting comments are
cautioned that we do not redact or edit personal identifying
information from comment submissions. You should submit only
information that you wish to make available publicly. All submissions
should refer to File Number SR-BOX-2019-05 and should be submitted on
or before April 8, 2019.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\11\
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    \11\ 17 CFR 200.30-3(a)(12).
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Eduardo A. Aleman,
Deputy Secretary.
[FR Doc. 2019-04947 Filed 3-15-19; 8:45 am]
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[Federal Register Volume 77, Number 159 (Thursday, August 16, 2012)]
[Notices]
[Page 49447]
[FR Doc No: 2012-20104]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0001]

Endocrinologic and Metabolic Drugs Advisory Committee; Notice of
Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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    This notice announces a forthcoming meeting of a public advisory
committee of the Food and Drug Administration (FDA). The meeting will
be open to the public.
    Name of Committee: Endocrinologic and Metabolic Drugs Advisory
Committee.
    General Function of the Committee: To provide advice and
recommendations to the Agency on FDA's regulatory issues.

DATES: Date and Time: The meeting will be held on October 18, 2012,
from 8 a.m. to 5 p.m.
    Location: FDA White Oak Campus, Building 31, the Great Room, White
Oak Conference Center (Rm. 1503), 10903 New Hampshire Ave., Silver
Spring, MD 20993-0002. Information regarding special accommodations due
to a disability, visitor parking, and transportation may be accessed
at: http://www.fda.gov/AdvisoryCommittees/default.htm; under the
heading ``Resources for You,'' click on ``Public Meetings at the FDA
White Oak Campus.'' Please note that visitors to the White Oak Campus
must enter through Building 1.
    Contact Person: Paul Tran, Center for Drug Evaluation and Research,
Food and Drug Administration, 10903 New Hampshire Ave., WO31-2417,
Silver Spring, MD 20993-0002,<PHONE_NUMBER>, Fax:<PHONE_NUMBER>,
email<EMAIL_ADDRESS>or FDA Advisory Committee Information Line,
1-800-741-8138<PHONE_NUMBER> in the Washington, DC area), to find out
further information regarding FDA advisory committee information. A
notice in the Federal Register about last minute modifications that
impact a previously announced advisory committee meeting cannot always
be published quickly enough to provide timely notice. Therefore, you
should always check the Agency's Web site at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm and scroll down to the
appropriate advisory committee meeting link, or call the advisory
committee information line to learn about possible modifications before
coming to the meeting.
    Agenda: The committee will discuss new drug application (NDA)
203568, mipomersen injection, by Genzyme Corporation. The proposed
indication (use) is as an adjunct to maximally tolerated lipid-lowering
medications and diet to reduce low-density lipoprotein (LDL)
cholesterol, apolipoprotein B, total cholesterol, non-high density
lipoprotein-cholesterol and lipoprotein (a) in patients with homozygous
familial hypercholesterolemia.
    FDA intends to make background material available to the public no
later than 2 business days before the meeting. If FDA is unable to post
the background material on its Web site prior to the meeting, the
background material will be made publicly available at the location of
the advisory committee meeting, and the background material will be
posted on FDA's Web site after the meeting. Background material is
available at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee link.
    Procedure: Interested persons may present data, information, or
views, orally or in writing, on issues pending before the committee.
Written submissions may be made to the contact person on or before
October 2, 2012. Oral presentations from the public will be scheduled
between approximately 1 p.m. and 2 p.m. Those individuals interested in
making formal oral presentations should notify the contact person and
submit a brief statement of the general nature of the evidence or
arguments they wish to present, the names and addresses of proposed
participants, and an indication of the approximate time requested to
make their presentation on or before September 24, 2012. Time allotted
for each presentation may be limited. If the number of registrants
requesting to speak is greater than can be reasonably accommodated
during the scheduled open public hearing session, FDA may conduct a
lottery to determine the speakers for the scheduled open public hearing
session. The contact person will notify interested persons regarding
their request to speak by September 25, 2012.
    Persons attending FDA's advisory committee meetings are advised
that the Agency is not responsible for providing access to electrical
outlets.
    FDA welcomes the attendance of the public at its advisory committee
meetings and will make every effort to accommodate persons with
physical disabilities or special needs. If you require special
accommodations due to a disability, please contact Paul Tran at least 7
days in advance of the meeting.
    FDA is committed to the orderly conduct of its advisory committee
meetings. Please visit our Web site at http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures
on public conduct during advisory committee meetings.
    Notice of this meeting is given under the Federal Advisory
Committee Act (5 U.S.C. app. 2).

    Dated: August 10, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-20104 Filed 8-15-12; 8:45 am]
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