*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : BY8925000 CHEMICAL NAME : Aniline, 4,4'-sulfonyldi- CAS REGISTRY NUMBER : 80-08-0 BEILSTEIN REFERENCE NO. : 0788055 REFERENCE : 4-13-00-01306 (Beilstein Handbook Reference) LAST UPDATED : 199710 DATA ITEMS CITED : 46 MOLECULAR FORMULA : C12-H12-N2-O2-S MOLECULAR WEIGHT : 248.32 WISWESSER LINE NOTATION : ZR DSWR DZ COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Human SYNONYMS/TRADE NAMES : * Avlosulfon * Avlosulphone * Benzenamine, 4,4'-sulfonylbis- * Bis(p-aminophenyl) sulfone * Bis(4-aminophenyl) sulfone * Bis(p-aminophenyl)sulphone * Bis(4-aminophenyl)sulphone * Croysulfone * Croysulphone * DADPS * Dapson * Dapsone * Dapsonum * DDS * DDS (pharmaceutical) * Diaminodifenilsulfona * 4,4-Diaminodifenylsulfon * Diamino-4,4'-diphenyl sulfone * p,p'-Diaminodiphenyl sulfone * 4,4'-Diaminodiphenyl sulfone * Diamino-4,4'-diphenyl sulphone * p,p-Diaminodiphenyl sulphone * 4,4'-Diaminodiphenyl sulphone * Di(p-aminophenyl) sulfone * Di(4-aminophenyl)sulfone * Di(p-aminophenyl)sulphone * Di(4-aminophenyl)sulphone * Diaphenylsulfon * Diaphenylsulfone * Diaphenylsulphon * Diaphenylsulphone * Diphenasone * Diphone * Disulone * DSS * Dubronax * Dumitone * Eporal * 1358F * F 1358 * Metabolite C * NCI-C01718 * Novophone * NSC-6091 * NSC 6091D * Sulfona * Sulfona-Mae * Sulfone UCB * 1,1'-Sulfonylbis(4-aminobenzene) * 4,4'-Sulfonylbisaniline * p,p-Sulfonylbisbenzamine * 4,4'-Sulfonylbisbenzamine * p,p-Sulfonylbisbenzenamine * 4,4'-Sulfonylbisbenzenamine * p,p'-Sulfonyldianiline * 4,4'-Sulfonyldianiline * Sulphadione * 1,1'-Sulphonylbis(4-aminobenzene) * p,p-Sulphonylbisbenzamine * 4,4'-Sulphonylbisbenzamine * p,p-Sulphonylbisbenzenamine * 4,4'-Sulphonylbisbenzenamine * Sulphonyldianiline * p,p-Sulphonyldianiline * 4,4'-Sulphonyldianiline * Sumicure S * Tarimyl * Udolac * WR 448 *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 112 mg/kg/4W-I TOXIC EFFECTS : Behavioral - muscle weakness Cardiac - pulse rate increase, without fall in BP Blood - oxidant related (GPD deficient) anemia REFERENCE : CEDEDE Clinical and Experimental Dermatology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1976- Volume(issue)/page/year: 20,155,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 300 mg/kg/21W-I TOXIC EFFECTS : Blood - eosinophilia REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 343,860,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 5 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - cyanosis REFERENCE : JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 19,1061,1982/1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 18 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - cyanosis Blood - methemoglobinemia-carboxyhemoglobin REFERENCE : AMSVAZ Acta Medica Scandinavica. (Almqvist & Wiksell, POB 45150, S-10430 Stockholm, Sweden) V.52-224, 1919-88. Volume(issue)/page/year: 214,215,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 18 gm/kg/15Y TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes Musculoskeletal - joints REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 1,78,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 28 mg/kg TOXIC EFFECTS : Blood - agranulocytosis REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 286,1244,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 36 mg/kg TOXIC EFFECTS : Blood - methemoglobinemia-carboxyhemoglobin REFERENCE : HUTODJ Human Toxicology. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants., RG 21 2XS, UK) V.1- 1981- Volume(issue)/page/year: 2,507,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 5,213,1955 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 196 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay) REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 183,36,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 250 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARTUA4 American Review of Tuberculosis. (New York, NY) V.1-70, 1917-54. For publisher information, see ARDSBL. Volume(issue)/page/year: 60,62,1949 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 313 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 48,336,1952 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 250 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARTUA4 American Review of Tuberculosis. (New York, NY) V.1-70, 1917-54. For publisher information, see ARDSBL. Volume(issue)/page/year: 60,62,1949 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 225 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 48,336,1952 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 357 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ANPSAI Archives of Neurology and Psychiatry. (Chicago, IL) V.1-64, 1919-50. For publisher information, see ARNEAS. Volume(issue)/page/year: 54,319,1945 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >4 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 28,313,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 300 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Mammal - domestic DOSE/DURATION : 200 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Behavioral - muscle contraction or spasticity Nutritional and Gross Metabolic - body temperature increase REFERENCE : BJPCAL British Journal of Pharmacology and Chemotherapy. (London, UK) V.1-33, 1946-68. For publisher information, see BJPCBM. Volume(issue)/page/year: 5,565,1950 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 1400 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936- Volume(issue)/page/year: 43(9),23,1978 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 6750 mg/kg/45D-C TOXIC EFFECTS : Related to Chronic Data - death REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 910 mg/kg/26W-I TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936- Volume(issue)/page/year: 43(9),23,1978 TYPE OF TEST : TCLo - Lowest published toxic concentration ROUTE OF EXPOSURE : Inhalation SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 44 mg/m3/17W-I TOXIC EFFECTS : Brain and Coverings - recordings from specific areas of CNS Kidney, Ureter, Bladder - proteinuria Nutritional and Gross Metabolic - changes in chlorine REFERENCE : TPKVAL Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv. Toxicology of New Industrial Chemical Substances. For English translation, see TNICS*. (Izdatel'stvo Meditsina, Moscow, USSR) No.1- 1961- Volume(issue)/page/year: 14,118,1975 TYPE OF TEST : TCLo - Lowest published toxic concentration ROUTE OF EXPOSURE : Inhalation SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 500 ug/m3/24H/13W-C TOXIC EFFECTS : Lungs, Thorax, or Respiration - structural or functional change in trachea or bronchi Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase REFERENCE : GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936- Volume(issue)/page/year: 43(5),3,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 150 mg/kg/3D-I TOXIC EFFECTS : Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count REFERENCE : IJMRAQ Indian Journal of Medical Research. (Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029, India) V.1- 1913- Volume(issue)/page/year: 57,1028,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 10800 mg/kg/45D-C TOXIC EFFECTS : Related to Chronic Data - death REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1890 mg/kg/30D-I TOXIC EFFECTS : Liver - other changes REFERENCE : NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: OTS0536152 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 20 gm/kg/80W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Blood - tumors REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1312 mg/kg/8W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 33,3069,1973 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 39 gm/kg/78W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Blood - tumors REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,1977 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 52 gm/kg/2Y-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - changes in spleen Musculoskeletal - tumors REFERENCE : IJCNAW International Journal of Cancer. (International Union Against Cancer, 3 rue du Conseil- General, 1205 Geneva, Switzerland) V.1- 1966- Volume(issue)/page/year: 25,123,1980 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 78450 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Endocrine - thyroid tumors REFERENCE : ALEPA8 Acta Leprologica. (3, pl. Claparede, 1205 Geneva, Switzerland) No.1- 1960- Volume(issue)/page/year: 53,11,1973 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 21840 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Blood - tumors REFERENCE : FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 25,619,1987 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 2100 mg/kg SEX/DURATION : male 6 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) REFERENCE : JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 81,259,1987 ** MUTATION DATA ** TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Human Leukocyte DOSE/DURATION : 4 mg/L REFERENCE : IJLEAG International Journal of Leprosy and Other Mycobacterial Diseases. (POB 1097, Bloomfield, NJ 07003) V.1- 1933- Volume(issue)/page/year: 43,41,1975 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,59,1980 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,59,1980 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,185,1987 TOXICOLOGY REVIEW IJDEBB International Journal of Dermatology. (J.B. Lippincott Co., E. Washington Sq., Philadelphia, PA 19105) V.9- 1970- Volume(issue)/page/year: 14,494,1975 TOXICOLOGY REVIEW JSIRAC Journal of Scientific and Industrial Research. (Pub. & Information Directorate, CSIR, Hillside Rd., New Delhi 110012, India) V.1-4, 1942-45; V.22- 1963- Volume(issue)/page/year: 34,521,1975 *** OCCUPATIONAL EXPOSURE LIMITS *** OEL-FINLAND;Carcinogen JAN 1993 OEL-RUSSIA:STEL 5 mg/m3 JAN 1993 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - T0798 No. of Facilities: 24 (estimated) No. of Industries: 2 No. of Occupations: 8 No. of Employees: 1510 (estimated) No. of Female Employees: 198 (estimated) *** STATUS IN U.S. *** EPA TSCA Section 8(b) CHEMICAL INVENTORY EPA TSCA Section 8(d) unpublished health/safety studies EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JUNE 1998 NCI Carcinogenesis Bioassay (feed);clear evidence:rat NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,77 NCI Carcinogenesis Bioassay (feed);no evidence:mouse NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-20,77 *** END OF RECORD ***