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Toxicity Effects

CAS Registry Number: 630-20-6

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 1,1,1,2-Tetrachloroethane
  • Ethane, 1,1,1,2-Tetrachloro- (8ci)(9ci)

Human Toxicity Excerpts

  • SIGNS AND SYMPTOMS: ... high percentage of large mononuclear cells found in circulating blood of patients suffering from early stages of tetrachloroethane poisoning. ... occasional complaints of tired feeling &, more often, gastric symptoms ... lack of appetite & slight nausea ... slight headache, & intercurrent remissions & exacerbations ... /tetrachloroethane/[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 767] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: In study of 380 workers ... in small factories in India ... tried to determine degree of inhalation of tetrachloroethane...used as cleaning agent. ... high % ... with nervous symptoms, such as headache, vertigo, nervousness, numbness & tremors. Tetrachloroethane @ 9-17 ppm induced tremors in 14% of the personnel; @ 40-74 ppm, in 33%; @ 50-61 ppm, in 41%; and @ 65-98 ppm, in 50%. /Tetrachloroethane/[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 768] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: In a study of the effects of chronic action of low concn of chlorinated hydrocarbons on production of various classes of immunoglobulins ... Rabbits ... Inhaled chlorinated hydrocarbons @ 2 mg/cu m for 3 hr/day for 8-10 mo. Tetrachloroethane was found to be more harmful to total antibody formation than its pentachloro- or dichloro- analogues. /tetrachloroethane/[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 768] **PEER REVIEWED**
  • GENOTOXICITY: ...nine mouse lymphoma assay (MLA) "unique positive' NTP rodent carcinogens were re-evaluated by an in vitro chromosomal aberration assay using Chinese hamster lung fibroblast cells (CHL/IU). Six of nine chemicals induced chromosomal aberrations; ... 1,1,1,2-tetrachloroethane induced numerical aberrations (polyploidy). ... The difference between the NTP results and /the results described here/ might be due to the use of different cell lines and protocols, and in some cases, to different interpretations of polyploidy.[Matsuoka A et al; Mutat Res 369 (3-4): 243-52 (1996)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: 1,1,1,2-Tetrachloroethane (>99% pure) was not mutagenic to Salmonella typhimurium TA1535, TA1537, TA98 or TA100 when tested at up to toxic doses (1000 ug/plate) in a preincubation assay without an exogenous metabolic system (S9). It was also reported to be nonmutagenic when tested in Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100 (using an unspecified protocol) in the presence or absence of Aroclor induced liver S9 (values not given).[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V41 92 (1986)] **PEER REVIEWED**
  • GENOTOXICITY: In a single study, 1,1,1,2-tetrachloroethane bound covalently to DNA in rats and mice in vivo. It induced gene mutations, sister chromatid exchanges and aneuploidy, but not chromosomal aberrations, in rodent cell cultures. It did not induce sex-linked recessive mutation in Drosophila or mutations or aneuploidy in yeast. 1,1,1,2-Tetrachloroethane induced gene conversion in yeast, genetic crossing-over and aneuploidy in fungus and gene mutations in bacteria.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. v71 1133 (1999)] **PEER REVIEWED**
  • GENOTOXICITY: Induced mitotic chromosome loss was assayed using diploid yeast strain S. cerevisiae D61.M. The test relies upon the uncovering and expression of multiple recessive markers reflecting the presumptive loss of the chromosome VII homologue carrying the corresponding wild-type alleles. .... The mammalian carcinogens, benzene, acrylonitrile, trichloroethylene, 1,1,1-trichloroethane and 1,1,1,2-tetrachloroethane failed to induce chromosome loss but elicited high levels of respiratory deficiency, reflecting anti-mitochondrial activity. ...[Whittaker SG et al; Mutat Res 241 (3): 225-42 (1990)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Seventy-two chemicals were tested for their mutagenic potential in the L5178Y tk+/- mouse lymphoma cell forward mutation assay, ... Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Significant responses were obtained with ... 1,1,1,2-tetrachloroethane ... rat liver S9 mix was not a requirement ...[McGregor DB et al; Environ Mol Mutagen 12 (1): 85-154 (1988)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: The genotoxic activity of 1,1,1,2-tetrachloroethane was studied by intraperitoneal administration of 127 uCi/kg body weight to male Wistar rats, followed by sacrifice at 22 hours and examination of covalent binding to tissues. The compound was bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The covalent binding index value was 40 in rat liver DNA, classifying it as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat organs were capable of bioactivating 1,1,1,2-tetrachloroethane in vitro. Liver fractions were most effective. Synergism was observed when both activating systems were present in the incubation mixture. This compound was metabolized by oxidative and reductive pathways, both dependent on cytochrome P450. It was also bioactivated by microsomal GSH transferases from liver and lung.[Colacci A et al; J Toxicol Environ Health 26 (4): 485-95 (1989)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Acute Exposure: AT 24 HR AFTER ORAL ADMIN OF 0.5 G 1,1,1,2-TETRACHLOROETHANE/KG TO RABBITS, BLOOD CHOLESTEROL & TOTAL LIPID LEVELS INCR & GLUTAMIC-PYRUVIC TRANSAMINASE, GLUTAMIC-OXALACETIC TRANSAMINASE, CREATINE PHOSPHOKINASE, LACTATE DEHYDROGENASE, AND ALPHA-HYDROXYBUTYRATE DEHYDROGENASE ACTIVITY WAS ENHANCED. EXCEPT FOR CREATINE PHOSPHOKINASE, ENZYME ACTIVITIES REMAIN ELEVATED @ 72 HR AFTER POISONING.[TRUHAUT R ET AL; J EUR TOXICOL 6 (2): 81-4 (1973)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Dogs exposed to vapors of tetrachloroethane have developed no corneal injury even though they underwent repeated /CNS depression/ ... . /Tetrachloroethane/[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 888] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: In rabbits, 1,1,1,2-tetrachloroethane was only slightly irritating to skin & ocular mucous membranes; its cutaneous LD50 was 20 g/kg. Acute toxicity by inhalation for exposure of 4 hr was similar in rats & rabbits, the LC50 being 2500 mg/cu m. After ingestion of 1,1,1,2-tetrachloroethane by rats & mice, LD50 values were 800 & 1500 mg/kg respectively. Hepatotoxic activity, incl formation of microvacuolizations & centrolobular necrosis was revealed.[TRUHAUT R ET AL; ARCH MAL PROF MED TRAV SECUR SOC 35 (6): 593-608 (1974)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 1,1,1,2-Tetrachloroethane was tested for carcinogenicity by oral administration by gavage in one study in mice and one study in rats. An increased incidence of hepatocellular adenomas was observed in mice of each sex and of hepatocellular carcinomas in females. The experiment in male rats gave negative results and that in female rats was inconclusive. In one small experiment in rats, no initiating or promoting activity of 1,1,1,2- tetrachloroethane was demonstrated.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. v71 1133 (1999)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The National Cancer Institute and National Toxicology Program have performed 2-year toxicology and carcinogenesis studies with a number of ethanes substituted with chlorine or bromine. ... In an attempt to determine some of the structure activity relationships involved in the induction of hyaline droplet nephropathy by halogenated ethanes, a series of commercially available ethanes substituted with three or more chlorines, four or more bromines, or a combination of chlorines and fluorines was studied in a short-term renal toxicity assessment in male F344/N rats. All chemicals were administered by gavage in corn oil to groups of five male rats once daily for 21 days. The doses selected for study, 0.62 and 1.24 mmol/kg per day, were based on those used in the 2-year pentachloroethane studies. The following chemicals were evaluated: 1,1,1,2- and 1,1,2,2-tetrachloroethane; pentachloroethane; 1,1,2,2-tetrachloro1,2-difluoroethane; 1,1,1-trichloro-2,2,2-trifluoroethane; 1,2-dichloro-1,1-difluoroethane; 1,1,1-trichloroethane; hexachloroethane; 1,1,1,2-and 1,1,2,2-tetrabromoethane; and pentabromoethane. ... For most groups, survival was not affected by chemical treatment; however, all rats ... administered 1.24 mmol/kg ...1,1,2,2-tetrachloroethane died before the end of the study. ... Increased kidney weights and signs of renal toxicity, indicated by urinalysis results, were noted in rats in many of the groups administered halogenated ethanes, but these observations were not always coincident with a diagnosis of hyaline droplet nephropathy. Hyaline droplet nephropathy was observed only in rats receiving penta-, hexa-, or 1,1,1,2-tetrachloroethane. ...[Toxic Rep Ser ;45: 1-C3 (1996)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: 1,1,1,2-TETRACHLOROETHANE (100-800 MUMOLE/KG/DAY FOR 7 DAYS, IP) IN MALE RATS INCR LIVER SUCCINATE DEHYDROGENASE, ACID PHOSPHATASE & GLUCOSE 6-PHOSPHATASE ACTIVITIES. LIVER DNA CONTENT DECR. WHITE CELL COUNT INCR; RED BLOOD CELL COUNT & BLOOD CHOLESTEROL DECR.[CHIERUTTINI ME, FRANKLIN CS; BR J PHARMACOL 57 (3): 421 (1976)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: 1,1,1,2-TETRACHLOROETHANE, GIVEN ORALLY IN AMT OF 0.30 G/KG BODY WT 5 DAYS/WK DURING 2 WK, INDUCES STEATOSIS ONLY IN FEMALE WISTAR RATS, WITH INCR IN TRIGLYCERIDES & DECR IN SOME LIVER ENZYMIC ACTIVITIES. MALE RATS SEEM TO BE RESISTANT.[TRUHAUT R ET AL; EUR J TOXICOL ENVIRON HYG 8 (3): 175-9 (1975)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LC50 RABBIT INHALATION 2500 MG/CU M/4 HR[TRUHAUT R ET AL; ARCH MAL PROF MED TRAV SECUR SOC 35 (6): 593-608 (1974)] **PEER REVIEWED**
  • LC50 Rat inhalation 2100 ppm/4 hr[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3376] **PEER REVIEWED**
  • LD50 MOUSE ORAL 1500 MG/KG[TRUHAUT R ET AL; ARCH MAL PROF MED TRAV SECUR SOC 35 (6): 593-608 (1974)] **PEER REVIEWED**
  • LD50 RABBIT PERCUTANEOUS 20 G/KG (20,000 MG/KG)[TRUHAUT R ET AL; ARCH MAL PROF MED TRAV SECUR SOC 35 (6): 593-608 (1974)] **PEER REVIEWED**
  • LD50 Rat oral 670 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3376] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • INHALATION OR INGESTION OF 1,1,1,2-TETRACHLOROETHANE BY PREGNANT RATS & RABBITS RESULTED IN PRESENCE OF HIGH LEVELS OF CHEM IN FETUSES, INDICATING TRANS-PLACENTAL PASSAGE.[TRUHAUT R ET AL; ARCH MAL PROF MED TRAV SECUR SOC 35 (6): 593-608 (1974)] **PEER REVIEWED**
  • It can be absorbed through inhalation, ingestion, skin and/or eye contact.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes Publications, 2002., p. 2162] **PEER REVIEWED**
  • WHEN ADMIN SC TO MICE, HALF OF DOSE OF 1,1,1,2-TETRACHLOROETHANE WAS EXHALED UNCHANGED, & PART METABOLIZED WAS EXCRETED MAINLY AS TRICHLOROETHANOL & TO MINOR EXTENT AS TRICHLOROACETIC ACID.[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 316] **PEER REVIEWED**

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Metabolism/Metabolites

  • ... /1,1,1,2-TETRACHLOROETHANE WAS/ METAB ... TO GIVE FIRST DICHLOROACETIC ACID AND THEN GLYOXYLIC ACID. WITH PART OF TETRACHLOROETHANE, NONENZYMIC DEHYDROCHLORINATION OCCURS, WITH FORMATION OF TRICHLOROETHYLENE, WHICH IS ALSO FOUND IN BREATH.[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 767] **PEER REVIEWED**
  • 1,1,1,2-TETRACHLOROETHANE WAS SC INJECTED INTO MICE & EXCRETION WAS FOLLOWED FOR 3 DAYS. THE PART METABOLIZED WAS EXCRETED MAINLY AS 2,2,2-TRICHLOROETHANOL (17-49% OF DOSE) & TO LESSER EXTENT AS TRICHLOROACETIC ACID.[YLLNER S; ACTA PHARMACOL TOXICOL 29 (5-6): 471-80 (1971)] **PEER REVIEWED**
  • 1,1,1,2-TETRACHLOROETHANE, WHEN ADMIN FOR 8 HR AS VAPOR @ 200 PPM TO RATS & MICE, PRODUCED THE FUJIWARA REACTION-POSITIVE URINARY METABOLITES TRICHLOROACETIC ACID, TRICHLOROETHANOL, & TOTAL TRICHLORO CMPD.[IKEDA M, OHTSUJI H; BRIT J IND MED 29 (1): 99-104 (1972)] **PEER REVIEWED**
  • IN RATS, GUINEA PIGS & RABBITS, 1,1,1,2-TETRACHLOROETHANE UNDERWENT DEHALOGENATION BY PRODUCING TRICHLOROETHANOL WHICH IS ELIMINATED PRINCIPALLY IN URINE IN FORM OF CONJUGATED GLUCURONIC DERIVATIVE (UROCHLORALIC ACID). OXIDN TO TRICHLOROACETIC ACID IS CONSIDERABLE ONLY IN RATS.[TRUHAUT R, PHU LICH N; J EUR TOXICOL 6 (4-5): 211-7 (1974)] **PEER REVIEWED**
  • In mice given a subcutaneous dose of 1.2-2.0 g/kg body weight 1,1,1,2-tetrachloroethane (< 0.1% impurities, including 0.03% trichloroethylene), 21-62% was eliminated unchanged in exhaled air within 72 hours. The major urinary metabolite (17-49% of the dose, although some fecal material was collected in the urine) was trichloroethanol and its glucuronide conjugate; trichloroacetic acid (1-7% of the dose) was also excreted in the urine. Trichloroethanol has also been isolated as the major metabolite, with trichloroacetic acid, from the urine of rats, rabbits and guinea pigs. After intraperitoneal administration of 1,1,1,2-tetrachloroethane to phenobarbital-treated rats, 1,1-dichloroethylene and 1,1,2-trichloroethane were detected in the blood.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V41 92 (1986)] **PEER REVIEWED**
  • In the presence of oxygen NADPH and rat liver microsomes, 1,1,1,2-tetrachloroethane undergoes little dechlorination. In contrast, NADPH-dependent reductive metabolism of 1,1,1,2-tetrachloroethane by hepatic microsomal fractions from rats yields 1,1,-dichloroethylene as the major metabolite.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V41 92 (1986)] **PEER REVIEWED**
  • Rat microsomes were prepared from livers of non-induced male Wistar rats; rabbit microsomes were from the livers of New Zealand white rabbits pretreated with three daily 20 mg/kg intraperitoneal injections of beta-naphthoflavone or with phenobarbital added to drinking water. Data was compared with purified cytochrome p450 enzymes isolated from rabbit liver in a reconstituted system of vesicles containing reductase, lipid, and cytochrome. The effects of the mixed function oxidase inhibitors, carbon monoxide and 100 micromolar SKF-525A, were also examined. In the absence of added substrate the rate of nicotinamide adenine dinucleotide phosphate (NADPH) oxidation was negligible, and on addition of substrate it proceeded linearly for at least 2 minutes. Using rat liver microsomes with hexachloroethane as substrate, 98% was inhibited by saturation with carbon monoxide and 37% inhibited by SKF-525A. The major product was tetrachloroethane, being produced in greater amounts anaerobically than aerobically.[Salmon AG et al; Br J Ind Med 42: 305-11 (1985)] **PEER REVIEWED** PubMed Abstract Full text: PMC1007477
  • The activity in vitro of liver microsomal enzymes to metabolize 1,1,1,2-tetrachloroethane was enhanced remarkably in 1-day fasted rats of both sexes, although fasting produced no significant increase in the microsomal protein and cytochrome p450 contents. Even the activity per whole liver was at a significantly increased level. A sex difference was noted in the metabolism of 1,1,1,2-tetrachloroethane both in fed and 1-day fasted rats.[Nakajima T, Sato A; Toxicol Appl Pharmacol 50 (3): 549-56 (1979)] **PEER REVIEWED** PubMed Abstract
  • Twenty-two hours after ip administration to male Wistar rats and BALB/c mice, 1,1,1,2-tetrachloroethane (1,1,1,2-TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1,1,1,2-TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1,1,1,2-TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incubation mixture a synergistic effect is observed. Unlike the related chemical 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE), which is bioactivated only through an oxidative route, 1,1,1,2-TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P-450. 1,1,1,2-TTCE is also bioactivated by microsomal GSH-transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.[Colacci A et al; J Toxicol Environ Health 26 (4): 485-95 (1989)] **PEER REVIEWED** PubMed Abstract

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Tsca Test Submissions

  • The ability of 1,1,1,2-tetrachloroethane to induce morphological transformation in the BALB/3T3 mouse cell line (Cell Transformation Assay) was evaluated. Based on preliminary toxicity determinations (exposure time= 3 days), 1,1,1,2-tetrachloroethane was tested at 0, 2, 10, 50 and 250 ug/ml, with cell survival ranging from 116% to 98% relative to untreated controls. None of the concentrations tested produced significantly greater transformation frequencies relative to untreated controls.[Arthur D. Little, Inc.; Cell Transformation Assays of 11 Chlorinated Hydrocarbon Analogs. (1983), EPA Document No. 40-8324457, Fiche No. OTS0509392] **UNREVIEWED**
  • The effects of 1,1,1,2-tetrachloroethane were examined in the rat hepatocyte primary culture/DNA repair assay. Based on preliminary toxicity tests, 1,1,1,2-tetrachloroethane was tested at concentrations of 1, 0.1, 0.01, 0.001, 1x10(-4) and 1x10(-5)% in DMSO solvent as the vehicle. The highest two levels were too cytotoxic to be evaluated in the assay. The concentrations at 0.01% or lower were nontoxic and did not cause a significant increase in the unscheduled DNA synthesis over the solvent control.[Naylor Dana Institute; DNA Repair Tests of 11 Chlorinated Hydrocarbon Analogs. (1983), EPA Document No. 40-8324292, Fiche No. OTS0509403] **UNREVIEWED**
  • The mutagenicity of 1,1,1,2-tetrachloroethane was evaluated in Salmonella tester strains TA1535, TA1537, TA98 and TA100 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat and mouse liver S9 fraction. Based on preliminary toxicity determinations, 1,1,1,2-tetrachloroethane, was tested at concentrations up to 10 mg/plate using the plate incorporation technique. 1,1,1,2-Tetrachloroethane did not cause a positive response in any tester strains with or without metabolic activation.[SRI International; Investigations of the Species Sensitivity and Mechanism of Carcinogenicity of Halogenated Hydrocarbons; Final Report, (1983), EPA Document No. 40+8424225, Fiche No. OTS0509408] **UNREVIEWED**

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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