# APPENDIX A-4

TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES

## TABLE A-4
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES

Compound CAS No. Target Organ Critical Effect Acenaphthene 83-32-9 Liver Hepatotoxicity Acetone 67-64-1 Liver Increased liver weights Kidney Increased kidney weights and nephrotoxicity Acetonitrile 75-05-8 Blood Decreased red blood cell counts and hematocrit Liver Hepatic lesions Acetophenone 98-86-2 GeneralGeneral toxicity Acrolein 107-02-8

- - No adverse effects observed Acrylonitrile 107-13-1 Reproductive Decreased sperm counts, seminiferous tubule degeneration Aldrin 309-00-2 Liver Hepatotoxicity Ammonia 7664-41-7 Sensory Decreased taste threshold Anthracene 120-12-7

- - No observed effects Antimony 7440-36-0 Blood Blood glucose and cholesterol, decreased longevity Aroclor 1016 12674-11-2 Reproductive system Decreased birth weights Aroclor 1254 11097-69-1 Eye Ocular exudate, inflamed and prominent meibomian glands General toxicity Distorted growth of fingers and toenails Immune system Decreased amtibody (IgM and IgG) response to sheep erythrocytes Arsenic, inorganic 7440-38-2 Skin Hyperpigmentation, keratosis, and possible vascular complications Barium 7440-39-3 Blood pressure Increased blood pressure Benzaldehyde 100-52-7 Gastrointestinal Forestomach lesions Kidney Kidney toxicity Benzidine 92-87-5 Liver Liver cell alterations in females Nervous system Brain cell vacuolization Benzoic acid 65-85-0

- - No observed effects Beryllium 7440-41-7

- - No adverse effects observed Biphenyl, 1,1

- 92-52-4 Kidney Kidney damage bis(2-Ethylhexyl)phthalate 117-81-7 Liver Increased relative liver weight bis(Chloromethyl)ether 542-88-1

- - No observed effects Bromodichloromethane 75-27-4 Kidney Renal cytomegaly Bromoform 75-25-2 Liver Hepatic lesions Butyl benzyl phthalate 85-68-7 Liver Significantly increased liver-to-body weight and liver-to-brain weight ratios

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 2 of 8)

Compound CAS No. Target Organ Critical Effect Cadmium 7440-43-9 Kidney Significant proteinuria Carbon disulfide 75-15-0 Reproductive Fetal toxicity and malformations Chlordane 57-74-9 Liver Hepatocyte regeneration Chlorine 7782-50-5

- - No observed effects Chloroaniline, 4

- 106-47-8 Spleen Nonneoplastic lesions of the splenic capsule Chlorobenzene Chlorobenzilate 108-90-7 510-15-6 Liver Gastrointestinal Histopathologic changes in liver Decreased stool quantity, food consumption, and body weight Nervous system Hyperirritability Chloroform 67-66-3 Liver Fatty cyst formation in liver Chloronaphthalene, 2

- 91-58-7 Respiratory Dyspnea, abnormal appearance, liver enlargement Chlorophenol, 2

- 95-57-8 Reproductive Reproductive effects Chlorotoluene, o

- 95-49-8 Body weight Decrease in body weight gain Chlorpyrifos 2921-88-2 Blood Decreased plasma cholinesterase activity Chromium 7440-47-3

- - No observed effects Chromium VI 18540-29-9

- - No observed effects Cresol, o-(2-methylphenol) 95-48-7 Body weight Decreased body weights Nervous system Neurotoxicity Cresol, p

- 106-44-5 Whole body Maternal death Nervous system Hypoactivity Respiratory Respiratory distress Cumene 98-82-8 Kidney Increased average kidney weight Cyanide 57-12-5

- - No observed effects Cyanogen 460-19-5 Body weight Weight loss Nervous system Myelin degeneration Thyroid Thyroid effects Cyanogen bromide 506-68-3 Body weight Weight loss Nervous system Myelin degeneration Thyroid Thyroid effects
Cyanogen chloride 506-77-4 Body weight Weight loss Neutroxicity Myelin degeneration Thyroid Thyroid effects

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 3 of 8)

Compound CAS No. Target Organ Critical Effect DDT, 4,4'

- 50-29-3 Liver Liver lesions Demeton 8065-48-3 Nervous system Cholinesterase inhibition Eye Optic nerve degeneration Diazinon 333-41-5 Blood Decreased cholinesterase activity Dibromochloromethane 124-48-1 Liver Hepatic lesions Dibromoethane, 1,2

- 106-93-4 Reproductive system Spermatogenic effects Dibutyl phthalate 84-74-2 Death Increased mortality Dichlorobenzene, o

- 95-50-1

- - No adverse effects observed Dichlorodifluoromethane (CFC-12) 75-71-8 Body weight Reduced body weight
Dichloroethane, 1,1

- 75-34-3

- - No observed adverse effects (route-to-route extrapolation) Dichloroethene, 1,1

- 75-35-4 Liver Hepatic lesions Dichloroethene, trans-1,2

- 156-60-5 Blood Increased serum alkaline phosphatase in male mice Dichloroethylene, cis-1,2

- 156-59-2 Organ weight Increased organ weight Respiratory hypertrophy/hyperplasia of the nasal respiratory epithelium Dichlorophenol, 2,4

- 120-83-2 Immunotoxicity Decreased delayed hypersensitivity response Dichlorophenoxyacetic 94-75-7 Blood Hematologic toxicity acid, 2,4

- (2,4-D acid) Kidney Hepatic toxicity Liver Renal toxicity Dichloropropene, 1,3

- 542-75-6 Organ weights Increased organ weights Dichlorvos 62-73-7 Nervous system Brain cholinesterase inhibition Blood Plasma red blood cell cholinesterase inhibition Dieldrin 60-57-1 Liver Liver lesions Diethyl phthalate 84-66-2 Body weight Decreased growth rate and food consumption Organ weight Altered organ weights Dimethylphenol, 2,4

- 105-67-9 General toxicity Lethargy, prostration, ataxia, Blood Hematological changes Dimethylphthalate 131-11-3 Kidney Kidney effects Dinitrobenzene, 1,2

- 528-29-0 Spleen Increased spleen weight Dinitrobenzene, 1,3

- 99-65-0 Spleen Increased spleen weight Dinitrobenzene, 1,4

- 100-25-4 Spleen Increased spleen weight

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 4 of 8)

Compound CAS No. Target Organ Critical Effect Dinitro-o-cyclohexyl phenol, 4,6

- 131-89-5 Eye Cataract formation
Dinitrophenol, 2,4

- 51-28-5 Eye Cataract formation Dinitrotoluene, 2,4

- 121-14-2 Gastrointestinal Heinze bodies and biliary tract hyperplasia Nervous system Neurotoxicity Dinitrotoluene, 2,6

- 606-20-2 Death Decreased survival Blood Heinze bodies, methemoglobinemia Gastrointestinal Hyperplasia of the bile duct Kidney Histopathologic changes in the kidney Nervous system Neurotoxic effects Di-n -octyl phthalate 117-84-0 Kidney Increased kidney weight Liver Increased liver weight; increased SGOT and SGPT activity Diphenylamine 122-39-4 Body weight Decreased body weight gain Kidney Increased kidney weight Liver Eye Increased liver weights Optic nerve degeneration Disulfoton 298-04-4 Nervous system Cholinesterase inhibition Endosulfan I 115-29-7 Body weight Decrease in body weight gain Nervous system Neurotoxicity Kidney Marked progressive glomerulonephrosis and blood vessel anurysms in males Endothall 145-73-3 Gastrointestinal Increased absolute and relative weights of stomach and small intestine Endrin 72-20-8 Nervous system Occasional convulsions Liver Mild histological lesions Epichlorohydrin 106-89-8 Kidney Kidney lesions (route-to-route extrapolation) Ethoxyethanol, 2

- 110-80-5 Body weight Decreased body weight Ethylbenzene 100-41-4 Kidney Kidney toxicity Liver Liver toxicity Ethylene glycol 107-21-1 Kidney Kidney toxicity Ethylene thiourea 96-45-7 Thyroid Increased incidence of thyroid hyperplasia Ethylmethacrylate 97-63-2 Kidney Increased relative weight of the kidney

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 5 of 8)

Compound CAS No. Target Organ Critical Effect Fluoranthene 206-44-0 Blood Hematological alterations and clinical effects Kidney Nephropathy Liver Increased liver weights Fluorene 86-73-7 Blood Decreased red blood cell count, packed cell volume and hemoglobin Formaldehyde 50-00-0 Body weight Reduced weight gain, histopathology in rats Formic acid 64-18-6 Body weight Decreased growth rate Freon 113 76-13-1 Nervous system Psychomotor impairment Furan 110-00-9 Liver Hepatic lesions Furfural 98-01-1 Liver Mild hepatocellular vacuolization Glycidaldehyde 765-34-4 Adrenal Enlarged adrenals Blood Hydropic renal pelvis and hematopoietic effects Body weight Retarded weight gain Heptachlor 76-44-8 Liver Liver weight increases in males only Heptachlor epoxide 1024-57-3 Liver Increased liver-to-body weight ratio Hexachlorobenzene 118-74-1 Liver Liver effects Hexachlorobutadiene 87-68-3 Kidney Renal tubules regeneration Hexachlorocyclopenta diene 77-47-4 Gastrointestinal Stomach lesions

Hexachloroethane Hexachlorophene 67-72-1 70-30-4 Kidney Salivary gland Atrophy and degeneration of renal tubules Swollen Brain and optic nerve Status spongiosis Hexane, n

- 110-54-3 Nervous system Neuropathy Respiratory Epithilial lesions in the nasal cavity Isophorone 78-59-1 Kidney Kidney pathology Malathione 121-75-5 Blood Red blood cell cholinesterase depression Maleic hydrazide 123-33-1 Kidney Renal dysfunction Malononitrile 109-77-3 Liver Liver effects Spleen Spleen effects Manganese 7439-96-5 Nervous system Central nervous system effects Mercuric chloride 7787-94-7 Immune system Autoimmune effects Mercury (inorganic) 7439-97-6 Nervous system Neurotoxicity Merphos 150-50-5 Nervous system Ataxia and delayed neurotoxicity

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 6 of 8)

Compound CAS No. Target Organ Critical Effect Wholebody Decreased body weight Methacrylonitrile 126-98-7 Liver Increased SGOT and SGPT levels Methanol 67-56-1 Nervous system Brain cholinesterase inhibition Blood Plasma red blood cell cholinesterase inhibition Methoxychlor 72-43-5 Reproductive Excessive loss of litter Methoxyethanol, 2

- 109-86-4 Reproductive Testicular effects (route-to-route extrapolation) Methyl acetate 79-20-9 Liver Increased alkaline phosphatase and increased SGPT Methyl bromide 74-83-9 Gastrointestinal Epithelial hyperplasia of the forestomach Methyl ethyl ketone 78-93-3 Reproductive Decreased fetal birth weight Methyl isobutyl ketone 108-10-1 Kidney Increased urinary protein Liver Increased absolute and relative weights of the liver Nervous system Lethargy Methyl mercury 22967-92-6 Nervous system Developmental neurological abnormalities in human infants Methyl parathione 298-00-0 Blood Red blood cell cholinesterase inhibition,reduced hemoglobin, hematocrit and red blood cells Methyl styrene (mixed isomers) 25013-15-4 Respiratory Nasal cavity lesions (route-to-route extrapolation)
Methylene bromide 74-95-3 Blood Increased carboxyhemoglobin (route-to-route extrapolation) Methylene chloride 75-09-2 Liver Liver toxicity Methylphenol, 108-39-4 Body weight Decreased body weights 3-(m-Cresol) Nervous system Neurotoxicity Naled 300-76-5 Nervous system Brain cholinesterase inhibition Nickel, soluble salts 7440-02-0 Body weight Decreased body weight Organ weight Decreased organ weights Nitroaniline, 2

- Nitrobenzene 88-74-4 98-95-3 Blood Adrenal Hematological effects Adrenal lesions Blood Hemolytic anemia Liver Renal lesions Renal Hepatic lesions N-nitrosodi-n -propylamine 621-64-7

- - No observed adverse effects Pentachlorobenzene 608-93-5 Kidney Kidney toxicity

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 7 of 8)

Compound CAS No. Target Organ Critical Effect Liver Liver toxicity Pentachloronitrobenzene 82-68-8 Liver Hepatotoxicity Pentachlorophenol 87-86-5 Kidney Kidney pathology Liver Liver pathology Phenol 108-95-2 Reproductive Reduced fetal body weight in rats Phorate 298-02-2 Nervous system Cholinesterase inhibition Phthalic anhydride 85-44-9 Kidney Histopathology Respiratory Lung damage Pronamide 23950-58-5

- - No observed effects Propargyl alcohol 107-19-7 Kidney Hepatotoxicity Liver Renal toxicity Propylene glycol 107-98-2 Kidney Histopathologic changes of the kidney monomethyl ether Liver Histopathologic changes of the liver Pyrene 129-00-0 Kidney Renal tubular pathology and decreased kidney weights Pyridine 110-86-1 Liver Increased liver weight Ronnel 299-84-3 Liver Liver effects Selenium 7782-49-2 Respiratory Clinical selenosis Silver 7440-22-4 Skin Argyria Strychnine and salts 57-24-9 General Toxicity and histopathology Styrene 100-42-5 Blood Red blood cell effects Liver Liver effects Tetrachlorobenzene, 1,2,4,5

- 95-94-3 Kidney Kidney lesions

Tetrachloroethane (carbon tetrachloride) 56-23-5 Liver Liver lesions
Tetrachloroethane, 1,1,1,2

- 630-20-6 Kidney Mineralization of the kidneys in males Liver Hepatic clear cell changes in females Tetrachloroethene 127-18-4 Liver Hepatotoxicity in mice, weight gain in rats Tetrachlorophenol, 2,3,4,6

- 58-90-2 Liver Increased liver weight and centrilobular hypertrophy Thallium 7440-28-0 Liver Increased levels of SGOT and LDH Toluene 108-88-3 Kidney Changes in kidney weights Liver Changes in liver weights

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998 TABLE A-4 (Continued)
TARGET ORGANS AND CRITICAL EFFECTS FOR COMPOUNDS WITH REFERENCE DOSE VALUES (Page 8 of 8)

Compound CAS No. Target Organ Critical Effect Toluene-2,6-diamine 823-40-5

- - No adverse effects observed Trichlorobenzene, 1,2,4

- 120-82-1 Adrenal Increased adrenal weights; vacuolation of zona fasciculate in the cortex Trichloroethane, 1,1,2

- 79-00-5 Blood Clinical serum chemistry Trichlorofluoramethane 75-69-4 Death Decreased survival (Freon 11) General Histopathology Trichlorophenol, 2,4,5

- 95-95-4 Kidney Kidney pathology Liver Liver pathology Trichloropropane, 1,2,3

- 96-18-4 Blood Alterations in clinical chemistry and reduction in red cell mass Trinitrobenzene, sym

- 99-35-4 Spleen Increased spleen weight Trinitrotoluene, 2,4,6

- 118-96-7 Liver Liver effects Vinyl acetate 108-05-4 Body weight Decreased body weight Kidney Altered kidney weight Xylenes 1330-20-7 Death Increased mortality Body weight Decreased body weight Nervous system Hyperactivity Xylene, m

- 108-38-3 Death Increase mortality Body weight Decreased body weight Nervous system Hyperactivity Xylene, o

- 95-47-6 Nervous system Hyperactivity Zinc 7440-66-6 Blood 47% 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. 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 RfDor 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) (U.S. EPA 1988).

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## RCRA Delisting Technical Support Background Document Appendix A-4 December 1998

References:
U.S. Environmental Protection Agency (EPA) 1988. Background Document—RfD Description and Use in Health Risk Assessments

. U.S.EPA. 1995. “Health Effects Assessment Summary Tables.”Fiscal Year-1995 Annual. Office of Solid Waste and Emergency Response. Washington, D.C. EPA/540/R-95/036. May. U.S.EPA. 1997. Intergrated Risk Information System. December.

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