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Toxicity Effects

CAS Registry Number: 7778-43-0

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

Names 1

    Human Toxicity Excerpts

    • ... AMONG WORKERS IN A FACTORY MANUFACTURING A SOLN OF SODIUM ARSENATE, ... RADIOGRAPHIC EXAMINATION DID NOT REVEAL ANY CASE OF BRONCHOGENIC CARCINOMA.[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 52] **PEER REVIEWED**
    • HEPTAHYDRATE: POISONOUS, BUT LESS SO THAN THE ARSENITE.[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1356] **PEER REVIEWED**
    • Sodium arsenate, at concn ranging from 6X10-9M to 6X10-8M, caused a small number of chromosomal aberrations (chromatid breaks, chromatid exchanges) in cultured human peripheral lymphocytes ... .[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. V23 95 (1980)] **PEER REVIEWED**
    • The ability of arsenic, nickel, & chromium compounds to induce transformation in cultured primary human diploid foreskin cells was studied. All nickel cmpds tested, lead chromate, potassium dichromate, chromic acid, dibasic sodium arsenate, NaAsO2 & N-methyl-N'nitro-N-nitrosoguanidine (MNNG) caused significant (p= 0.001) dose dependent inductions of anchorage independent colonies. ... Anchorage independent cell strains derived from metal salt treated cells were not resistant to the cytotoxicity of metal salts, indicating metal salts induced rather than selected for anchorage independence. ...[Biedermann KA, Landolph JR; Cancer Res 47 (14): 3815-23 (1987)] **PEER REVIEWED** PubMed Abstract

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    Non-Human Toxicity Excerpts

    • A single ip injection of 45 mg/kg bw sodium arsenate to Swiss-Webster mice on one of days 6-11 of pregnancy resulted in an incr rate of fetal resorptions, growth retardation and a variety of malformations - predominantly fusion or forking of ribs, exencephaly, shortened jaw, open eyes, anophthalmia, etc ... .[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. V23 90 (1980)] **PEER REVIEWED**
    • Acute arsenic (As) administration produced in rat liver a decreased in the heme saturation of trypotophan pyrrolsase (TP), accompanied by dose-related increases in 5-aminolevulinate synthetase (ALAS) and heme oxygenase (HO) activities, along with a corresponding decrease in cytochrome p450 concn. The relationship between heme synthesis and degradation was altered as a result of As treatment. The magnitude of these effects was related to the oxidation state of arsenic, sodium arsenite (AsIII) being more potent than sodium arsenate (AsV). These results support the contention that the heme saturation of trypotophan pyrrolsase is sensitive to treatments that modify liver heme concn. The increase in heme oxygenase activity produced by arsenic appears to be mediated by a mechanism largely or entirely independent of heme. The main effects of continous exposure to sodium arsenite were an initial decrease in the heme saturation of trypotophan pyrrolsase which remained constant during the period of treatment, and an initial increase in 5-aminolevulinate synthetase activity, which after ten days of exposure dropped somewhat but remained aboved control values.[Cebri'an ME et al; J Biochem Toxicol 3: 77-86 (1988)] **PEER REVIEWED** PubMed Abstract
    • An increased incidence of chromosomal abnormalities was detected in rats given oral doses of sodium arsenate (4 mg/kg/day As) for 2 to 3 weeks, but no consistent increase in chromosomal aberrations was detected in bone marrow cells or spermatogonia from mice given sodium arsenite (about 50 mg/kg/day As) for up to 8 weeks. These studies suggest that ingested arsenic cause chromosomal effects and genetic damage in rodents.[Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 432] **PEER REVIEWED**
    • Arsenate-induced renal agenesis was studied in detail in Wistar rat fetuses after a single ip injection of 45 mg/kg bw sodium arsenate of day 10 of pregnancy. Following treatment, the mesonephric duct failed to give rise to an uretric bud, with subsequent failure of inuction of the metanephric blastema ... .[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. V23 91 (1980)] **PEER REVIEWED**
    • Arsenic (As) has been found at elevated concentrations in irrigation drainwater and in aquatic plants utilized by waterfowl. Mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) or diets containing 30, 100, or 300 ppm arsenic added as sodium arsenate. After 10 weeks blood and tissue samples were collected for biochemical and histological examination. Arsenic accumulated significantly in brain and liver of ducklings fed 100 or 300 ppm but did not result in histopathological lesions. The 300 ppm dietary arsenic concentration decreased overall growth (weight gain) in males, whereas all concentrations of arsenic decreased overall growth and rate of growth in females. Food consumption was less during the first three weeks in all 300 ppm group and during the second week for the 100 ppm compared to controls. Plasma sorbitol dehydrogenase activity and plasma glucose concentration were higher in the 300 ppm group compared to controls. Plasma triglyceride concentration increased in a arsenic treated groups. Brain ATP was lower in the 300 ppm group and sodium/potassium-dependant ATPase activity was higher in the 30 and 100 ppm groups. Hepatic glutathione peroxidase activity was lower in the 300 ppm group and malondialdehyde lower in all treatment groups. All treatment levels caused elevation in hepatic glutathione and ATP concentrations.[Camardese MB et al; Environ Toxicol Chem 9 (6): 785-96 (1990)] **PEER REVIEWED**
    • Cows and dogs were fed sodium arsenite and sodium arsenate daily for five days. Urine was collected and analyzed for methylarsenate and inorganic arsenate. In the cow, the levels rose to 0.1 to 0.5 and 1.0 to 4.0 ppm, respectively. When the cows were returned to normal diets, all values returned to control levels (0.02 to 0.10 ppm and 0.1 to 0.2 ppm). In dogs, arsenite feeding produced identical peak values 5.0 to 7.0 ppm for both methylarsenate and inorganic arsenate. Feeding of sodium arsenate to dogs produced a rise to 10 ppm methylarsenate and 5.0 ppm inorganic arsenate. Six days after withdrawal from the arsenic-containing diet, all values reached control levels.[Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 23] **PEER REVIEWED**
    • Cytotoxicity, morphological neoplastic transformation, cellular uptake and metabolic reduction were determined in BALB/3T3 Cl A31-1-1 cells for trivalent arsenic (sodium arsenite, As3+) and for pentavalent arsenic (sodium arsenate, As5+). The levels of cellular uptake of (73)As labelled sodium arsenite and arsenate were dose-dependent and highest in the first hr. At equimolar concentration (3 X 10(-6) M), cellular uptake was 4-fold higher for sodium arsenite than for sodium arsenate. Cytotoxicity was higher for sodium arsenite than for sodium arsenate, but when correlated to total arsenic cell burden it showed no significant difference for the two forms. Morphological transformation focus assays showed transforming activity for both sodium arsenite and sodium arsenate with relative transformation frequencies also of approximately 4:1. Recovery from the cytosol after exposure for 1-24 hr was greater than 90% for either form of absorbed arsenic. Exposure to sodium arsenite yielded 100% as sodium arsenite in cytosol but exposure to sodium arsenate yielded greater than 70% as sodium arsenite, showing a high rate of intracellular metabolic reduction. No methylated metabolites were detected by ion-exchange chromatography. After 24 hr incubation in cell-free medium, oxidation of sodium arsenite to sodium arsenate occurred up to 30% of the dose, but incubation in the presence of cells lowered the oxidation level to 4% sodium arsenate was recovered unchanged from cell-free medium (24 hr incubation), but in the presence of the cells it yielded up to 5% as sodium arsenite within 24 hr and the cumulative release of sodium arsenite by cells exposed to sodium arsenate was dose-dependent. Glutathione depletion by diethylmaleate inhibited reduction of sodium arsenate to sodium arsenite by these cells to 25% of controls, showing that sodium arsenate reduction is partly dependent on glutathione.[Bertolero F et al; Carcinogenesis 8 (6): 803-8 (1987)] **PEER REVIEWED** PubMed Abstract
    • Embryotoxic effects of two inorganic arsenic compounds, sodium arsenite and sodium arsenate, on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with three to five somites exposed to 1-40 uM sodium arsenite or to 10-400 uM sodium arsenate were cultured for 48 hours and their development was compared with that of control embryos. Sodium arsenite proved to be teratogenic between 3 and 4 uM and embryolethal at higher concentrations; sodium arsenate had similar activity but at concentrations ten times higher than for sodium arsenite. Both compounds produced a growth retardation and a similar pattern of defects. Growth retardation was indicated by a statistically significant reduction in crown-rump length, head length, and yolk sac diameter. Abnormal embryos were characterized by hypoplasia of the prosencephalon with open neural tube, hydropericardium, somite abnormalities, and failure of development of limb buds and sensory placodes. These results confirm that both sodium arsenate and sodium arsenite are embyrotoxic compounds and that the activity occurs at concentrations ten times lower than for sodium arsenate.[Chaineau E et al; Teratol 41 (1): 105-12 (1990)] **PEER REVIEWED**
    • Even though arsenic is a well established carcinogen in humans, there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promotor in two-stage models of carcinogenicity in mice. Two arsenic salts (sodium arsenite and sodium arsenate) induced a high frequency of methotrexate resistant /mouse/ 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene. Sodium arsenite was active at a lower concn than sodium arsenate. Sodium arsenate induced methotrexate resistant /mouse 3T6/ cell colonies at concentrations of 150 to 300 nM.[Lee TC et al; Science 241 (4861): 79-81 (1988)] **PEER REVIEWED** PubMed Abstract
    • Male ICR mice in groups of 5 were given ip or oral doses of four arsenic (As) compounds: Sodium meta- arsenite, 5, 10, and 15 mg arsenic/kg; sodium arsenate, 10, 20, and 30 mg arsenic/kg; sodium dimethylarsenate (DMA), 100, 300, and 500 mg arsenic/kg; sodium methylarsenate, 100, 300, and 500 mg arsenic/kg. The amounts of induced hepatic zinc thioneine were determined. Toxicity for ip administration, as measured by lethality, was in the order of m-arsenite > arsenate > sodium dimethylarsenate > sodium methylarsenate; thus, the inorganic compounds were much more toxic than the organic arsenic compounds. There were no deaths following oral administration. All compounds caused the formation of induced hepatic zinc-thioneine, and induction was not dependent upon the mode of administration of arsenic. Induction was observed at much lower doses of inorganic than organic compounds.[Maitani T et al; Toxicol Lett 39 (1): 63-70 (1987)] **PEER REVIEWED** PubMed Abstract
    • Of 19 female Swiss mice, 11 developed lymphomas or lymphocytic leukemia following 20 weekly iv injections of 0.5 mg/kg bw arsenic given as a 0.005% aqueous soln of sodium arsenate ... .[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. V23 88 (1980)] **PEER REVIEWED**
    • Pregnant CD-1 mice were treated with 20 ip or 40 ip mg/kg sodium arsenate on gestation day 18 (pluged= day 1). Individual fetuses, pooled placentas and maternal blood, urine, liver, and kidneys were obtained from three or more litters at intervals up to 24 hours following treatment. Acid-digested samples were analyzed for total arsenic by hydride generation atomic absorption spectrophotometry. The rate of arsenic elimination from maternal samples was not influenced by administration route. First-order elimination followed a brief period of distribution, and the biological half-life was approximately 10 hr. Arsenic was found in most samples, with mean peak concentrations expressed as ug arsenic/g (wet wt) or /ml (values listed are post-treatment sampling times in minutes or hours and concentrations for ip and for po treated groups, respectively) as follows: fetuses-2, 3.5; 6, 0.8, placentas-2, 9.3; 1, 2.3, blood-10 minutes, 6.9; 1, 2.0, urine-1, 712; 2, 342, kidney-20 minutes, 25.4; 1, 11.0, liver-0.5, 7.9; 1, 11.7. By 24 hours, arsenic levels in fetuses and placentas had declined to 0.22 ug/g and 0.74 ug/g for ip and 0.33 ug/ g and 0.57 ug/g for po treatments, respectively. Fetal arsenic uptake and loss were more rapid following ip than po treatments, and although the ip dose was only half that used po, peak fetal A+5 was almost fivefold higher following ip treatment.[Hood RD et al; Teratol 35 (1): 19-25 (1987)] **PEER REVIEWED**
    • Production of teratogenic lesions in hamsters following continuous exposure to arsenate, in combination with short term maternal heat stress during the critical phase of organogenesis, was examined. On day 6 of gestation, 4 groups of Syrian hamsters were implanted with either 0.321 or 0.482 M of radiolabeled sodium arsenate. On day eight of gestation, one group from each dose level was incubated at 39 deg C for 50 min. Dams were sacrificed on day 13, & the fetuses recovered for exam. An elevation in maternal body temperature occurred during heat treatment, & subsided within 15 min posthyperthermia. Exposure to heat at both arsenic dose levels produced increased concns of arsenic in maternal blood & placentas. Maternal blood arsenic levels in heat treated dams dropped to levels measured in nonheat treated dams within 2 or 3 hrs post hyperthermia. Elevated placental concns of arsenic were prolonged relative to maternal blood levels, & remained elevated for a longer period of time in the 0.482 M dose group. A higher % of litters with malformed fetuses was produced by heat treated dams. In hamsters treated with arsenate & heat stressed during critical organogenesis, a rise in placental arsenic concns causes an incr in fetal malformations.[Hanlon DP, Ferm VH; Teratol 34 (2): 189-93 (1986)] **PEER REVIEWED**
    • Sodium arsenate administered to dogs and cats in doses sufficient to cause severe chronic poisoning has caused /numerous incidences of/ conjunctivitis, but no abnormality of the pupils or ophthalmoscopically visible abnormalities. Sodium arsenate injected into the carotid artery in rabbits in doses that were commonly lethal in one to six days caused no ophthalmoscopically recognizable changes in the retina. However, in one cat poisoned for a month with arsenate, microscopically demonstrable abnormalities in the ganglion cells and inner nuclear layer /was reported/.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 117] **PEER REVIEWED**
    • Sprague-Dawley rats were given deionized water containing 40 or 85 ppm sodium arsenate and food ad libitum for 6 wk. Prolonged exposure of rats to sodium arsenate in drinking water for 6 wk resulted in a progressive coproporphyrinuria which was consistent with dose and duration of metal exposure. Urinary coproporphyrin concentrations incr progressively in both 40 and 85 ppm treatment groups, reaching 3.3- and 5.5-fold control levels, respectively, at 5 wk of exposure. Renal coprogen oxidase activity was decreased to 73% and 60% of control kidney enzyme activity at 6 wk following onset of treatment with sodium arsenate at 40 or 85 ppm, respectively. Changes in renal coprogen oxidase activities accompanied an increase in total tissue arsenic concentrations, which reached 7 and 13 ug/g of renal tissue at 40 and 85 ppm respectively, after 5 wk of exposure. Rats injected ip with 75 mg/kg of sodium arsenate showed significantly incr concentrations of urinary coproporphyrin 24 hr after treatment and a substantial decr in renal, but not hepatic, coprogen oxidase activity. Renal coprogen oxidase activity in rats treated acutely with sodium arsenate was decr to 21% of that measured in kidneys of untreated animals. Sodium arsenate added in vitro to mitochondrial preparations of untreated rat livers or kidneys to achieve final concentrations of 0.1 mM, 1.0 mM, or 10.0 mM produced the following % change in coprogen oxidase activity over control values, respectively: in liver, 96, 91, and 84%; and in kidney, 72, 63, and 55%.[Woods JS, Southern MR; Toxicol Appl Pharmacol 97 (1): 183-90 (1989)] **PEER REVIEWED** PubMed Abstract
    • Syrian golden hamsters were given sodium arsenite (AsIII) solution, sodium arsenate (AsV) solution, arsenic trisulfide (AsIII) suspension or lead arsenate (AsV) suspension, orally or intratracheally, and the relationship between tissue retention and metabolism of arsenic and the solubility and chemical form of the arsenic compounds administered was studied. Solubilities varied, as did the amount of the administered dose retained at the injection site. Whole body retention of (74)As was influenced both by the route of administration and the chemical form of the compound given. Retention times were longer with intratracheal administration than with oral, especially for arsenic trisulfide and lead arsenate. The extremely low whole body retention of arsenic following oral administration of lead arsenate and arsenic trisulfide was probably due to a low gastrointestinal absorption, as indicated by the excretion of 70 to 80% percent of the doses in the feces. With the exception of lead arsenate, which was largely retained in the lungs, approximately 60% of the intratracheal doses was excreted in the urine within 3 days. Urinary metabolites of arsenic varied greatly with the route of administration and the chemical form. When administered intratracheally, the relative amount of the three metabolites was about the same for the two arsenate compounds, although the absolute amounts were lower for the less soluble lead arsenate than for the soluble sodium arsenate. When administered orally, the sodium arsenate was rapidly excreted in the urine, largely unaltered.[Marafante E, Vahter M; Environ Res 42 (1): 72-82 (1987)] **PEER REVIEWED** PubMed Abstract
    • The concentration, availability, and chemical composition of arsenic (As) in the plasma and red cells in hamster dams was investigated. Pregnant Syrian hamsters were injected ip with 64.2 uM/kg of (74)As labeled sodium arsenate at 8:00 AM on the eighth day of gestation. Arsenate and its metabolites in plasma and red cells were determined by ion exchange chromatography. Arsenite and the methylated arsenic speies were separated using a moidified Ag50 method. Tightly bound arsenic and low molecular weight metabolites in red cells were separated by lysing the cells, acidifying, removing arsenate on Dowex2 resin, and separating arsenite and methylate species with ethanol. The concn of arsenic in whole blood rose to 222 uM/kg within approximately 30 min postinjection and then declined to a low of 6.0 uM/kg after five hr. A similar trend was observed in plasma where the high during the same period was 358 and low 5.6 uM/kg, respectively. In the red cells the high level of arsenic was 100 and the low 6.45 uM/kg in the indicated study period. All plasma arsenic was found in the ethanol supernatant fractions. Initially 99% of plasma arsenic was in the arsenate form and 1% was present as dimethylarsinate (DMA). After five hr arsenate declined to 36, arsenite increased to 15, and dimethylarsinate rose to 53% on the average. The arsenic was also taken up rapidly by the liver, kidney, and placenta. The total concentration in these tissues was similar to that in maternal blood.[Hanlon DP, Ferm VH; Environ Res 40 (2): 380-90 (1986)] **PEER REVIEWED** PubMed Abstract
    • The teratogenic and embryotoxic effects of constant rate exposure to arsenic were studied in hamsters. Pregnant hamsters were implanted with osmotic minipumps containing aquious sodium arsenate at concentrations of 150, 175, 200, 225, or 250 mg/ml on days 4 to 7 of gestation. Controls were implanted with minipumps filled with demineralized water. On day 13 of gestation, the animals were killed, their uteri were removed, and examined. Resorption sites and evidence of embryonic or fetal death were recorded. Live fetuses were examined for external malformations and then weighed and measured for crown/rump length. The amounts of arsenic which the mothers had received by day 8 of gestation ranged from 0.0346 to 0.0538 mM/kg. The incidence of malformations (severe neural tube defects and rib malformations) depended only on the concentration of sodium arsenate in the minipumps. Resorption rates, fetal weights and crown/rump lengths decreased with increasing exposure time and increasing sodium arsenate concentration.[Ferm VH, Hanlon DP; Environ Res 37 (2): 425-32 (1985)] **PEER REVIEWED** PubMed Abstract
    • When Wistar rats were treated with 20-40 mg/kg bw sodium arsenate ip once on days 8-12 of pregnancy, a high percentage of malformed fetuses was observed. The main malformations were eye defects, exencephaly, gonadal or renal agenesis and rib or vertebral abnormalities. At higher doses, the rate of resorptions was incr dramatically ... .[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. V23 91 (1980)] **PEER REVIEWED**

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    Human Toxicity Values

    • None found

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    Non-Human Toxicity Values

    • MLD RATS IP 50 MG/KG /SODIUM ARSENATE HEPTAHYDRATE/[The Merck Index: An Encyclopedia of Chemicals and Drugs 8th ed. Rahway, New Jersey: Merck and Co., Inc., 1968., p. 953] **PEER REVIEWED**

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    Absorption, Distribution And Excretion

    • None found

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    Metabolism/Metabolites

    • None found

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    Tsca Test Submissions

    • None found

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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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