APPENDIX A-2 TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES

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1 APPENDIX A-2

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3 TABLE A-2 (Page 1 of 7) Acenaphthene Hepatotoxicity Acetone Increased liver weights Increased kidney weights and nephrotoxicity Acetonitrile Decreased red blood cell counts and hematocrit Hepatic lesions Acetophenone General General toxicity Acrolein No adverse effects observed Acrylonitrile Reproductive Decreased sperm counts, seminiferous tubule degeneration Aldrin Hepatotoxicity Ammonia Sensory Decreased taste threshold Anthracene No observed effects Antimony glucose and cholesterol, decreased longevity Aroclor Reproductive system Decreased birth weights Aroclor Eye Ocular exudate, inflamed and prominent meibomian glands General toxicity Immune system Distorted growth of fingers and toenails Decreased amtibody (IgM and IgG) response to sheep erythrocytes Arsenic, inorganic Skin Hyperpigmentation, keratosis, and possible vascular complications Barium pressure Increased blood pressure Benzaldehyde Gastrointestinal Forestomach lesions toxicity Benzidine cell alterations in females Brain cell vacuolization Benzoic acid No observed effects Beryllium No adverse effects observed Biphenyl, 1, damage bis(2-ethylhexyl)phthalate Increased relative liver weight bis(chloromethyl)ether No observed effects Bromodichloromethane Renal cytomegaly Bromoform Hepatic lesions Butyl benzyl phthalate Significantly increased liver-to-body weight and liver-to-brain weight ratios Cadmium Significant proteinuria Carbon disulfide Reproductive Fetal toxicity and malformations Chlordane Hepatocyte regeneration Chlorine No observed effects Region 6 A-2-1

4 (Page 2 of 8) Chloroaniline, Spleen Nonneoplastic lesions of the splenic capsule Chlorobenzene Histopathologic changes in liver Chlorobenzilate Gastrointestinal Decreased stool quantity, food consumption, and body weight Hyperirritability Chloroform Fatty cyst formation in liver Chloronaphthalene, Respiratory Dyspnea, abnormal appearance, liver enlargement Chlorophenol, Reproductive Reproductive effects Chlorotoluene, o Body weight Decrease in body weight gain Chlorpyrifos Decreased plasma cholinesterase activity Chromium No observed effects Chromium VI No observed effects Cresol, o-(2-methylphenol) Body weight Decreased body weights Neurotoxicity Cresol, p Whole body Maternal death Respiratory Hypoactivity Respiratory distress Cumene Increased average kidney weight Cyanide No observed effects Cyanogen Body weight Weight loss Thyroid Myelin degeneration Thyroid effects Cyanogen bromide Body weight Weight loss Thyroid Myelin degeneration Thyroid effects Cyanogen chloride Body weight Weight loss Neutroxicity Thyroid Myelin degeneration Thyroid effects DDT, 4,4' lesions Demeton Cholinesterase inhibition Eye Optic nerve degeneration Diazinon Decreased cholinesterase activity Dibromochloromethane Hepatic lesions Dibromoethane, 1, Reproductive system Spermatogenic effects Dibutyl phthalate Death Increased mortality Dichlorobenzene, o No adverse effects observed Dichlorodifluoromethane (CFC-12) Body weight Reduced body weight Region 6 A-2-2

5 (Page 3 of 8) Dichloroethane, 1, No observed adverse effects (route-to-route extrapolation) Dichloroethene, 1, Hepatic lesions Dichloroethene, trans-1, Increased serum alkaline phosphatase in male mice Dichloroethylene, cis-1, Organ weight Increased organ weight Respiratory hypertrophy/hyperplasia of the nasal respiratory epithelium Dichlorophenol, 2, Immunotoxicity Decreased delayed hypersensitivity response Dichlorophenoxyacetic acid, 2,4- (2,4-D acid) Hematologic toxicity Hepatic toxicity Renal toxicity Dichloropropene, 1, Organ weights Increased organ weights Dichlorvos Brain cholinesterase inhibition Dieldrin lesions Plasma red blood cell cholinesterase inhibition Diethyl phthalate Body weight Decreased growth rate and food consumption Organ weight Altered organ weights Dimethylphenol, 2, General toxicity Lethargy, prostration, ataxia, Hematological changes Dimethylphthalate effects Dinitrobenzene, 1, Spleen Increased spleen weight Dinitrobenzene, 1, Spleen Increased spleen weight Dinitrobenzene, 1, Spleen Increased spleen weight Dinitro-o-cyclohexylphenol, 4, Eye Cataract formation Dinitrophenol, 2, Eye Cataract formation Dinitrotoluene, 2, Gastrointestinal Heinze bodies and biliary tract hyperplasia Neurotoxicity Dinitrotoluene, 2, Death Decreased survival Gastrointestinal Heinze bodies, methemoglobinemia Hyperplasia of the bile duct Histopathologic changes in the kidney Neurotoxic effects Di-n-octyl phthalate Increased kidney weight Diphenylamine Body weight Decreased body weight gain Increased liver weight; increased SGOT and SGPT activity Increased kidney weight Increased liver weights Region 6 A-2-3

6 (Page 4 of 8) Disulfoton Eye Optic nerve degeneration Cholinesterase inhibition Endosulfan I Body weight Decrease in body weight gain Neurotoxicity Marked progressive glomerulonephrosis and blood vessel anurysms in males Endothall Gastrointestinal Increased absolute and relative weights of stomach and small intestine Endrin Occasional convulsions Mild histological lesions Epichlorohydrin lesions (route-to-route extrapolation) Ethoxyethanol, Body weight Decreased body weight Ethylbenzene toxicity toxicity Ethylene glycol toxicity Ethylene thiourea Thyroid Increased incidence of thyroid hyperplasia Ethylmethacrylate Increased relative weight of the kidney Fluoranthene Hematological alterations and clinical effects Nephropathy Increased liver weights Fluorene Decreased red blood cell count, packed cell volume and hemoglobin Formaldehyde Body weight Reduced weight gain, histopathology in rats Formic acid Body weight Decreased growth rate Freon Psychomotor impairment Furan Hepatic lesions Furfural Mild hepatocellular vacuolization Glycidaldehyde Adrenal Enlarged adrenals Body weight Hydropic renal pelvis and hematopoietic effects Retarded weight gain Heptachlor weight increases in males only Heptachlor epoxide Increased liver-to-body weight ratio Hexachlorobenzene effects Hexachlorobutadiene Renal tubules regeneration Hexachlorocyclopentadiene Gastrointestinal Stomach lesions Hexachloroethane Atrophy and degeneration of renal tubules Region 6 A-2-4

7 (Page 5 of 8) Hexachlorophene Salivary gland Swollen Brain and optic nerve Status spongiosis Hexane, n Neuropathy Respiratory Isophorone pathology Epithilial lesions in the nasal cavity Malathione Red blood cell cholinesterase depression Maleic hydrazide Renal dysfunction Malononitrile effects Spleen Spleen effects Manganese Central nervous system effects Mercuric chloride Immune system Autoimmune effects Mercury (inorganic) Neurotoxicity Merphos Ataxia and delayed neurotoxicity Wholebody Decreased body weight Methacrylonitrile Increased SGOT and SGPT levels Methanol Brain cholinesterase inhibition Methoxychlor Reproductive Excessive loss of litter Plasma red blood cell cholinesterase inhibition Methoxyethanol, Reproductive Testicular effects (route-to-route extrapolation) Methyl acetate Increased alkaline phosphatase and increased SGPT Methyl bromide Gastrointestinal Epithelial hyperplasia of the forestomach Methyl ethyl ketone Reproductive Decreased fetal birth weight Methyl isobutyl ketone Increased urinary protein Increased absolute and relative weights of the liver Lethargy Methyl mercury Developmental neurological abnormalities in human infants Methyl parathione Red blood cell cholinesterase inhibition,reduced hemoglobin, hematocrit and red blood cells Methyl styrene (mixed isomers) Respiratory Nasal cavity lesions (route-to-route extrapolation) Methylene bromide Increased carboxyhemoglobin (route-to-route extrapolation) Methylene chloride toxicity Methylphenol, 3-(m-Cresol) Body weight Decreased body weights Neurotoxicity Naled Brain cholinesterase inhibition Nickel, soluble salts Body weight Decreased body weight Organ weight Decreased organ weights Nitroaniline, Hematological effects Region 6 A-2-5

8 (Page 6 of 8) Nitrobenzene Adrenal Adrenal lesions Renal Hemolytic anemia Renal lesions Hepatic lesions N-nitrosodi-n-propylamine No observed adverse effects Pentachlorobenzene toxicity toxicity Pentachloronitrobenzene Hepatotoxicity Pentachlorophenol pathology pathology Phenol Reproductive Reduced fetal body weight in rats Phorate Cholinesterase inhibition Phthalic anhydride Histopathology Respiratory Lung damage Pronamide No observed effects Propargyl alcohol Hepatotoxicity Propylene glycol monomethyl ether Renal toxicity Histopathologic changes of the kidney Histopathologic changes of the liver Pyrene Renal tubular pathology and decreased kidney weights Pyridine Increased liver weight Ronnel effects Selenium Respiratory Clinical selenosis Silver Skin Argyria Strychnine and salts General Toxicity and histopathology Styrene Red blood cell effects effects Tetrachlorobenzene, 1,2,4, lesions Tetrachloroethane (carbon tetrachloride) lesions Tetrachloroethane, 1,1,1, Mineralization of the kidneys in males Hepatic clear cell changes in females Tetrachloroethene Hepatotoxicity in mice, weight gain in rats Tetrachlorophenol, 2,3,4, Increased liver weight and centrilobular hypertrophy Thallium Increased levels of SGOT and LDH Toluene Changes in kidney weights Changes in liver weights Region 6 A-2-6

9 (Page 7 of 8) Toluene-2,6-diamine No adverse effects observed Trichlorobenzene, 1,2, Adrenal Increased adrenal weights; vacuolation of zona fasciculate in the cortex Trichloroethane, 1,1, Clinical serum chemistry Trichlorofluoramethane (Freon 11) Death Decreased survival General Histopathology Trichlorophenol, 2,4, pathology pathology Trichloropropane, 1,2, Alterations in clinical chemistry and reduction in red cell mass Trinitrobenzene, sym Spleen Increased spleen weight Trinitrotoluene, 2,4, effects Vinyl acetate Body weight Decreased body weight Altered kidney weight Xylenes Death Increased mortality Body weight Decreased body weight Hyperactivity Xylene, m Death Increase mortality Body weight Decreased body weight Hyperactivity Xylene, o Hyperactivity Zinc % decrease in erythrocyte superoxide dismutase concentration in females Note: Target organ and critical effect information presented in this table is intended only to provide the information needed to break down calculated hazard quotients for various chemicals, based on the target organs that they affect (see Section 7.3 of the HHRAP). The information is intended to be neither (1) an exhaustive list of the potential toxic effects of a compound, or (2) an indication that toxicological studies for a substance are inadequate because the target organ or critical effect for each particular substance is limited to one or two reported health effects. The noncancer reference dose (RfD) for ingestion exposure, or the reference concentration (RfC) for inhalation exposures, is generally based on the experimental dose that produces no adverse effects in the most sensitive laboratory animal tested (referred to as the no-observed-adverse effects-level [NOAEL]). If all of the doses used in experimental studies produce some effect, the lowest dose at which an adverse effect is observed (referred to as the lowest-observed-adverse-effect-level) is used to determine the RfD or RfC. Both uncertainty factors and modifying factors are included in the calculation of RfDs to ensure that these values are protective of human health (see Appendix A-3) ( 1988). Region 6 A-2-7

10 References: U.S. Environmental Protection Agency (EPA) Background Document RfD Description and Use in Health Risk Assessments. U.S.EPA Health Effects Assessment Summary Tables. Fiscal Year-1995 Annual. and Emergency Response. Washington, D.C. EPA/540/R-95/036. May. U.S.EPA Intergrated Risk Information System. December. Region 6 A-2-8