Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 7784-46-5 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Sodium arsenite
  • SODIUM META-ARSENITE

Human Toxicity Excerpts

  • A 29 yr old man was found unresponsive a few min after self injecting undetermined amounts of potassium cyanide & sodium arsenite iv in a suicide attempt. Treatment with the Lilly Cyanide Antidote kit rapidly resolved the initial coma, despite a whole blood cyanide level of 4.4 ug/ml. A 12 hr urine arsenic collection begun on admission showed 10,065 ug arsenic/12 hr. The patient received im BAL initially, which was followed by two 10-day courses of oral D-penicillamine. Complications included upper gi tract bleeding requiring transfusion, transient elevations of liver function tests, self limited complaints of decreased vision with conjunctival hyperemia & photophobia, & an abscess at the injection site. Although specific antidote therapy completely resolved the cyanide toxicity, early & prolonged arsenic chelation did not prevent a mild sensory peripheral neuropathy from developing with onset about 17 days after self injection. [DiNapoli J et al; Ann Emerg Med 18 (3): 308-11 (1989)]**PEER REVIEWED**
  • Accumulation of heme oxygenase mRNA is strongly stimulated by treatment of cultured human skin fibroblasts with uv radiation, hydrogen peroxide, or the sulfhydryl reagent sodium arsenite. Since this will result in a transient reduction in the prooxidant state of cells, the phenomenon may represent an important inducible antioxidant defense mechanism. To examine the generality of the response, we have measured the accumulation of the specific mRNA in a variety of human & mammalian cell types after inducing treatments. Induction by sodium arsenite is observed in all addnl human cell types tested. This includes primary epidermal keratinocytes & lung & colon fibroblasts as well as established cell lines such as HeLa, TK6 lymphoblastoid, & transformed fetal keratinocytes. Strong induction of heme oxygenase mRNA is also observed following sodium arsenite treatment of cell lines of rat, hamster, mouse, monkey, & marsupial origin. The agents which lead to induction in cultured human skin fibroblasts fall into 2 categories: (a) those which are oxidants or can generate active intermediates (uv A radiation, hydrogen peroxide, menadione, & the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate); (b) agents which are known to interact with or modify cellular glutathione levels (buthionine sulfoximine, sodium arsenite, iodoacetamide, diamide, & cadmium chloride). [Applegate LA et al; Cancer Res 51 (3): 974-8 (1991)]**PEER REVIEWED**
  • Very young children may be more susceptible. Study of 291 exposure incidents involving a single kind of ant bait in the form of a bottle containing 1/2 oz (15 mL) of sweetened 0.61% sodium arsenite soln permitted a poison control center to conclude that a dosage of <1 mg/kg can cause serious illness in a child & 2 mg/kg can cause death. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 550]**PEER REVIEWED**
  • A cross-sectional study of workers at a factory where sodium arsenite was prepared found that workers with the highest arsenic exposure (mean air levels ranging from 0.384 to 1.034 mg As/m3 and estimated to avg 0.613 mg As/m3) tended to be grossly pigmented with hyperkeratinization of exposed skin and to have multiple warts ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 37 (2000)]**PEER REVIEWED**
  • ... SODIUM ARSENITE ... HAS ... BEEN FOUND POTENT IN PRODUCING SKIN LESIONS OF VERY VARIED CHARACTER. /ONE INVESTIGATOR/ ... DESCRIBED ULCERATION OF HANDS & FEET, SCROTUM & PERINEUM FROM ITS USE AS VERMIN KILLER, & /ANOTHER/ ... REPORTED ERYTHEMA, PAPULES & ULCERATIONS FROM ITS USE AS INSECTICIDE. [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 46]**PEER REVIEWED**
  • Sodium arsenite, at concn ranging from 3X10-9M to 6X10-8M caused chromosomal aberrations (chromatid breaks, chromatid exchanges) in cultured human peripheral lymphocytes and in human diploid fibroblast WI.38 and MRC5 cell lines ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 94 (1980)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... EFFECT OF SODIUM ARSENITE ON DEVELOPMENT OF CHICK EMBRYOS. INJECTION OF SUBLETHAL CONCN OF ARSENIC INTO EGGS PRODUCED ECTOPIC CONDITIONS, BUT NO MONSTROSITIES ... . [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 339]**PEER REVIEWED**
  • MICE WERE: ... ADMIN SINGLE DOSE OF SODIUM ARSENATE OR ARSENITE BY IP INJECTION ON SPECIFIC DAY FROM 6TH-12TH DAY OF GESTATION & ... RESULTS /OBSERVED/ ON 18TH DAY. INJECTIONS GIVEN ON 9TH DAY ... MOST TERATOGENIC; 60% OF 96 IMPLANTATIONS ... RESORBED OR DEAD, & 63% ... GROSSLY MALFORMED. DEFECTS INCLUDED EXENCEPHALY, MICROGNATHIA, PROTRUDING TONGUE, AGNATHIA, OPEN EYE, CLEFT LIP, FUSED VERTEBRAE, & FORKED RIBS. ... TERATOGENIC EFFECTS ... @ 45 MG/KG, 25 MG/KG ... WITHOUT EFFECT. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 340]**PEER REVIEWED**
  • ... SODIUM ARSENITE INHIBITED INDUCTION OF INTERFERON IN RABBIT KIDNEY CELL CULTURES. IT WAS FOUND, HOWEVER, THAT, ALTHOUGH HIGH CONCN OF ARSENITE INHIBITED ACTION OF EXOGENOUS MOUSE INTERFERON ADDED TO CULTURES OF MOUSE EMBRYO CELLS, LOW CONCN OF ARSENITE INCR ANTIVIRAL ACTIVITY OF LOW CONCN OF INTERFERON. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 336]**PEER REVIEWED**
  • IN RATS FED SODIUM ARSENATE OR ARSENITE @ EQUAL ARSENIC LEVELS, THOSE RECEIVING ARSENATE HAD LESS SEVERE CHANGES IN BILE DUCT ENLARGEMENT. SIMILAR RESULTS IN RATS WERE OBTAINED WHEN GROWTH & SURVIVAL WERE USED AS CRITERIA. [Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 437]**PEER REVIEWED**
  • SEVERE SKIN INJURY HAS FOLLOWED ACCIDENTAL SPRAYING OF DAIRY CATTLE WITH 60% SODIUM ARSENITE ... [Clarke, E.G., and M. L. Clarke. Veterinary Toxicology. Baltimore, Maryland: The Williams and Wilkins Company, 1975., p. 39]**PEER REVIEWED**
  • IN LEUKOCYTE CULTURES TREATED WITH SODIUM ARSENITE @ 0.29-1.8X10-8 MOLAR FOR LAST 48 HR OF CULTURE PERIOD, 60% OF 148 METAPHASES EXAM ... /HAD/ CHROMATID BREAKS. ... CHROMOSOMAL DAMAGE ... IN DIPLOID FIBROBLASTS TO WHICH ... /IT/ WAS ADDED FOR LAST 24 HR OF CULTURE; CHROMATID BREAKS ... IN 20% OF 459 METAPHASES EXAMINED. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 332]**PEER REVIEWED**
  • Studies on laboratory animals indicate that arsenic can impair resistance to viral infections. Increased mortality from viral infections among mice exposed to arsenic was reported. The mice were given arsenic sc at the time of inoculation or in drinking water 2 wk before innoculation. The sc doses were 2-4 mg arsenic/kg body wt as sodium arsenite or arsenic (III) oxide and the drinking water doses 75-150 mg arsenic/l as sodium arsenite or sodium arsenate. The viruses were pseudorabies, encephalomyocarditis, and St. Louis encephalitis viruses. Mice given ip injections of sodium arsenite (1.8 mg arsenic/kg body weight) were lessprotectic homopolynucleotide complex) against encephalomyocarditis virus than the controls. The protective action of poly I/poly C against viruses was reported to be associated with interferon formation. [WHO; Environ Health Criteria: Arsenic p.106 (1981)]**PEER REVIEWED**
  • When a single ip injection of 10 or 12 mg/kg bw sodium arsenite was given to Swiss-Webster mice on days 9-12 of pregnancy, there was a high rate of resorptions, and the surviving fetuses showed various malformations of the eyes, ribs, tail and brain ... . [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 90 (1980)]**PEER REVIEWED**
  • SODIUM ARSENITE INDUCED POINT MUTATIONS IN TWO STRAINS OF ESCHERICHIA COLI WP2 AT DOSES OF 0.16 TO 0.8 MMOL, ALLOWING 40% SURVIVAL OF COLONY FORMATION; NEGATIVE RESULTS WERE OBTAINED IN A REC A STRAIN. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 94 (1980)]**PEER REVIEWED**
  • PREGNANT MICE WERE GIVEN A SINGLE ORAL DOSE OF 20, 40 OR 45 MG SODIUM ARSENITE/KG ON ONE OF DAYS 8-15 OF PREGNANCY. A LOW INCIDENCE OF GROSS MALFORMATIONS OCCURRED IN LITTERS FROM THE 40 AND 45 MG/KG GROUPS, ONLY WHEN TREATMENT OCCURRED ON DAY 8, 9, OR 10 OF GESTATION. FETAL MORTALITY SIGNIFICANTLY INCREASED WITH THE 40 MG/KG DOSE ADMIN ON DAYS 10 OR 12, OR WITH THE 45 MG/KG DOSE ADMINISTERED ON DAYS 10, 12, 13, 14, OR 15. VISCERAL EXAM, LIGHT MICROSCOPY, AND SKELETAL ANALYSIS REVEALED NO TREATMENT EFFECTS. [BAXLEY MN ET AL; BULL ENVIRON CONTAM TOXICOL 26 (6): 749-56 (1981)]**PEER REVIEWED**
  • MALE MICE WERE EXPOSED TO SODIUM ARSENITE FOR 3 WK IN DRINKING WATER AT 3 OR 4 CONCN RANGING FROM 0.5-10.0 PPM. THE HUMORAL COMPONENT OF THE IMMUNE SYSTEM WAS SUBSEQUENTLY EVALUATED USING HEMAGGLUTINATION, RADIAL IMMUNODIFFUSION AND THE CUNNINGHAM PLAQUE ASSAY (BOTH PRIMARY AND SECONDARY IMMUNE RESPONSE). A MAX IMMUNOSUPPRESSIVE EFFECT WAS PRODUCED IN MOST INSTANCES AT A METAL CONCENTRATION LESS THAN 2.0 PPM. [BLAKLEY BR ET AL; TOXICOL APPL PHARMACOL 52 (2): 245-54 (1980)]**PEER REVIEWED**
  • TREATMENT OF PREGNANT HAMSTERS WITH AN ORAL DOSE OF 20 MG SODIUM ARSENITE/KG ON DAYS 9 OR 10 OF GESTATION OR WITH 25 MG/KG ON DAY 11 OF GESTATION HAD NO EFFECT ON PRENATAL GROWTH OR SURVIVAL. HOWEVER, TREATMENT WITH THE HIGHER DOSE ON DAYS 8 OR 12 INCREASED PRENATAL DEATHS AND INHIBITED PRENATAL GROWTH BY THE 12 DAY FETUS. NO FETAL DEFECTS WERE OBSERVED, BUT SOME MATERNAL DEATHS OCCURRED. SOME GROSS MALFORMATIONS WERE INDUCED BY 2.5 OR 5 MG SODIUM ARSENITE/KG ADMINISTERED IP IN ADDITION TO GROWTH INHIBITION AND MORTALITY. [HOOD RD, HARRISON WP; BULL ENVIRON CONTAM TOXICOL 29 (6): 671-8 (1982)]**PEER REVIEWED**
  • PREGNANT SPRAGUE-DAWLEY RATS WERE GIVEN A SINGLE IP INJECTION OF AN AQUEOUS SOLUTION OF SODIUM ARSENITE (11 MG/KG OF MATERNAL BODY WT) ON ONE OF DAYS 6-12 OF GESTATION. ARSENITE TREATMENT RESULTED IN A SIGNIFICANT INCREASE IN FETAL DEATHS WHEN ADMIN DURING DAYS 6-10 (57-61% RESORPTION), WITH THE EXCEPTION OF DAY 8 (32% RESORPTIONS). A SIGNIFICANT DECREASE IN FETAL WEIGHTS WAS OBSERVED. THE MOST FREQUENT SOFT-TISSUE MALFORMATIONS WERE BRAIN AND EYE DEFECTS, WHICH PREDOMINATED ON DAYS 7-9, WHILE SKELETAL DEFECTS (RIBS AND VERTEBRAE) PREDOMINATED ON DAY 10. [UMPIERRE CC; TERATOLOGY 23 (2): 66A (1981)]**PEER REVIEWED**
  • ... Sodium arsenite ... /was/ tested for its genotoxic effects in Saccharomyces cerevisiae. ... Sodium arsenite was virtually ineffective as a convertogen but gave a positive result for reversion. [Kharab P, Singh I; Mutat Res 155 (3): 117-120 (1985)]**PEER REVIEWED**
  • Cytotoxicity, chromosome aberrations, and mutations to 6-thioguanine resistance were synergistically increased by incubating the ultraviolet light (UV)-irradiated Chinese hamster ovary (CHO) cells in medium containing sodium arsenite. However, the frequencies of sister-chromatid exchanges and mutations to ouabain resistance induced by UV were not synergistically increased by sodium arsenite. The synergistic effect of sodium arsenite on UV-induced chromosome aberrations varied with cell-harvesting time and decreased with increasing time intervals between UV and sodium arsenite treatments. [Lee TC et al; Mutat Res 148 (1-2): 83-89 (1985)]**PEER REVIEWED**
  • The ip LD50's of N-(2,3-dimercaptopropyl)phthalamidic acid and British Anti-Lewisite were 0.819 and 1.48 mol/kg, respectively, in male albino mice. The ip ED50 of N-(2,3-dimercaptopropyl)phthalamidic acid and British Anti-Lewisite for the prevention of the lethal effects of 0.15 mmol sodium arsenite 2/kg was 0.022 and 0.169 mmol/kg, respectively, N-(2,3-dimercaptopropyl)phthalamidic acid increased the LD50 of sodium arsenite by approximately 2.5-fold following two ip injections of 0.20 mmol N-(2,3-dimercaptopropyl)phthalamidic acid/kg. The effectiveness of N-(2,3-dimercaptopropyl)phthalamidic acid in reducing the toxicity of sodium arsenite was further demonstrated by its reversal of the sodium arsenite inhibition of pyruvate dehydrogenase multienzyme complex activity in vitro. Similarly, in an in vivo experiment in which mice received 0.10 mmol sodium arsenite/kg, and 30 min later given 0.05 or 0.10 mmol/kg N-(2,3-dimercaptopropyl)phthalamidic acid, there was a rapid recovery of PDH activity. The distribution of (74)Arsenic in the tissues of male New Zealand rabbits was altered following im injection of 0.20 mmol/kg N-(2,3-dimercaptopropyl)phthalamidic acid. Under these conditions, the concn of (74)Arsenic was significantly decreased. For all tissues tested, the (74)Arsenic content decreased by at least 50% as compared to that of untreated controls. N-(2,3-dimercaptopropyl)phthalamidic acid was effective also in increasing both urinary and fecal excretion of arsenic. The stability of aqueous solutions of N-(2,3-dimercaptopropyl)phthalamidic acid varies with the pH of the solution. N-(2,3-dimercaptopropyl)phthalamidic acid is more stable in an acid solution. [Stine ER et al; Toxicol Appl Pharmacol 75 (2): 329-336 (1984)]**PEER REVIEWED**
  • The neurotoxicity of As was detected with light and electron microscopy. Fetal mouse (17 day) spinal ganglia and newborn mouse cerebellum cultures were exposed to various concn of sodium arsenite for different periods. Pathological changes were observed at 3X10-6 M concn. Nerve cells which were most vulnerable of As toxicity, displayed dilation of rough endoplasmic reticulum, swelling of mitochondria, and increased numbers of lysosomes after 3 days. After 5 days exposure, some nerve cells underwent necrosis. The pathological changes in nerve tissues continued for 7-10 days, after which the necrotic cells decreased in number and surviving cells were observed after 30 days. The sensitivity of nervous tissues to arsenic toxicity changed during a long exposure period. [Yoskioka A; Kyoto-furtsu Ika Daigaku Zasshi 93 (12): 1023-1038 (1984)]**PEER REVIEWED**
  • Mortality rates for newly hatched /muskellunge/ fry were low during the first 7 days of the experiment. Prior to swim-up, fry were inactive and did not appear to be affected by arsenic. No LC50 concn could be determined for fry during this stage of development. Swim-up began on day 8 in all tanks and was accompanied by a rapid rise in mortality in those fry exposed to arsenic. Fry exposed to 5.0 mg/l As went from 23% mortality on day 8 to 50% mortality on day 9. Fry exposed to 1.0 mg/l arsenic went from 13% mortality on day 8 to 47% mortality on day 12. Fry exposed to 0.05 mg/l arsenic went from 12% mortality on day 8 to 21% on day 11 and 46% on day 13. All fry exposed to arsenic died by day 15 post-hatch, 7 days after the start of swim-up. Control fish completed swim-up in 3 days (day 11 after hatching), began to feed and appeared normal. The 96 hr LC50 for swim-up fry (determined geographically) was 1.1 mg/l arsenic. Five week old fry exposed to arsenic for 96 hr had a 20% mortality at 1.0 mg/l and a 70% mortality at 5.0 mg/l. A LC50 value for these fry of 2.6 mg/l was found. Twelve week old fry exposed to arsenic for 96 hr had a 30% mortality at 15 mg/l and 100% mortality at 20 mg/l. A LC50 value for these fry of 16.0 mg/l was found. There was a rapid change in the tolerance of muskellunge fry to arsenic as development progressed. Concn of arsenic tolerated by 12 week old fry were toxic to 5 week old fry, and concn tolerated by 5 week old fry were lethal to newly hatched fry undergoing swim-up. However, concn toxic to fry during swim-up had not affected these fry during their pre swim-up period of development. Water quality did not appear to affect these results. [Spotila JR, Paladino FV; Comp Biochem Physiol 62C: 67-69 (1979)]**PEER REVIEWED**
  • Spiking feed with 0.5 mg sodium arsenite/kg (0.5 ppm) stimulated growth of laying hens without altering blood parameters. [Chupakhina OK; Veterinariya (Moscow) 7: 69 (1983)]**PEER REVIEWED**
  • Administration of sodium arsenite to mice in doses of 10 or 12 mg/kg body weight (6 or 7 mg arsenic/kg weight) resulted in a lower incidence of malformations and a higher incidence of resorptions than sodium arsenate at 11 mg arsenic/kg body weight. [WHO; Environ Health Criteria: Arsenic p.93 (1981)]**PEER REVIEWED**
  • A two-yr feeding study on the effects of sodium arsenite and sodium arsenate administered in the food of Osborne-Mendel rats and beagle dogs. Weight records were kept, blood samples were taken periodically, and animals were killed and autopsied. Postmortem tissues were preserved for microscopic study. In rats, masked enlargement of the common bile duct was observed at the highest dosage of both compounds (250 and 400 ppm for the arsenate, respectively). At the next lower dosages of both (125 and 250 ppm), enlargement was present but less pronounced. Arsenite slightly reduced survival and both compd caused reduced weight. Some changes were noted in the hematologic study. None of the dogs on the highest arsenite dosage (125 ppm) survived for 2 yr but 5 of the 6 on the highest arsenate dosage (125 ppm) did survive. In the non-survivors, gross and microscopic changes were essentially those of inanition. All dogs on the highest dosage lost much weight, but those at levels of 50 ppm or less did not differ from controls. No carcinogenic effect of these two arsenicals could be detected. [Bryon WR et al; Toxicol Appl Pharmacol 10: 132-147 (1967) as cited in NIOSH; Criteria Document: Inorganic Arsenic p.58 (1975) DHEW Pub. NIOSH 75-149]**PEER REVIEWED**
  • Weanling Long-Evans rats were used to evaluate the effects of arsenic by being fed diets low in arsenic (0.46 ug arsenic/g wet weight) and administering sodium arsenite in the drinking water of experimental animals at a level of 5 ug arsenic/ml. The experiment continued until the natural death of the animals. No specific disorders were observed in the control or experimental groups, nor was there a carcinogenic or tumorigenic effect. No arsenical keratoses were observed. The growth rates and life spans of the 2 groups did not differ. However, male rats had elevated serum cholesterol levels and lower glucose levels than did the controls. Arsenic accumulated with age in all tissues analyzed. [Schroeder HA; J Nutr 96: 37-45 (1968) as cited in NIOSH; Criteria Document: Inorganic Arsenic p.59 (1975) DHEW Pub. NIOSH 75-149]**PEER REVIEWED**
  • A 5 ug oral dose given for 3 months caused 69% mortality (control 70%) and up to 19.3% weight decr in the mouse. [Nat'l Research Council Canada; Effects of Arsenic in the Canadian Environment p.218 (1978) NRCC No. 15391]**PEER REVIEWED**
  • ... 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 arsenite 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**
  • Male ICR mice in groups of 5 were given ip or oral doses of four arsenic compounds: Sodium m-arsenite, 5, 10, and 15 mg arsenic/kg; sodium arsenate, 10, 20, and 30 mg arsenic/kg; sodium dimethylarsenate, 100, 300, and 500 mg arsenic/kg; sodium methylarsenate, 100, 300, and 500 mg arsenic/kg. The amounts of induced hepatic zinc-thionein 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-thionein, 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**
  • Experimentally, acute poisoning of rabbits and rats with sodium arsenite has caused no retinal degeneration. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 117]**PEER REVIEWED**
  • CULTURES OF E COLI ... EXPOSED TO UV LIGHT AND THEN PLATED IN PRESENCE OR ABSENCE OF SODIUM ARSENITE. SURVIVAL AFTER IRRADIATION OF WILD-TYPE E COLI ... DECR BY 0.5 MMOLAR ARSENITE. ... EFFECT ... SEEN IN STRAINS UNABLE TO CARRY OUT EXCISION REPAIR, SUGGESTING ... ARSENITE INHIBITS 1 OR MORE STEPS IN /DNA/ POSTREPLICATION REPAIR ... [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 332]**PEER REVIEWED**
  • THE ADMIN OF SODIUM ARSENITE TO RATS PRODUCED PROFOUND INDUCTION OF MICROSOMAL HEME OXYGENASE (EC 1.14.99.3) IN LIVER AND KIDNEY AND A DECREASE IN CYTOCHROME P 450 CONTENT. [SARDANA MK ET AL; THE POTENT HEME OXYGENASE INDUCING ACTION OF ARSENIC AND PARASITICIDAL ARSENICALS; PHARMACOLOGY 23 (5): 247-53 (1981)]**PEER REVIEWED**
  • Effect of sodium arsenite on ornithine decarboxylase activity was studied in cultured murine erythroleukemia cells. In stationary phase cells, ornithine decarboxylase activity was not detectable, but it could be induced within a few hr by dilution of the cells in fresh medium. Sodium arsenite prevented this induction of ornithine decarboxylase activity measured 5 hr after cell dilution. A 50% inhibition was produced at 1.2 uM and virtually complete inhibition was produced at a concentration of 10 uM or higher. However, addition of sodium arsenite (0.2 mM) 5 hr after cell dilution, ie, when ornithine decarboxylase waS already induced, stabilized the enzyme after an initial decline. The half-life of ornithine decarboxylase activity, measured after cycloheximide (0.2 mM) treatment, increased almost six fold after addition of sodium arsenite (0.2 mM). [Flamigni F et al; Cell Biochem Funct 7 (3): 213-7 (1989)]**PEER REVIEWED**
  • The effects of certain monovalent, divalent, and trivalent metals on a mitochondiral preparation of K+-stimulated-p-nitrophenylphosphatase from rat brain were studied. Except for salts of nickel(2+), selenium(2+), and tithium(2+), which did not produce 50% inhibition, all of the metals examined were potent inhibitors of the enzyme with a 15- value of 490 uM for arsenic(3+). ... The order of their potency was silver(1+)> mercury(2+) > copper(2+) : zinc(2+) > cobalt(2+) > iron(2+) > lead(2+) > iorn(3+) > manganese(2+) > arsenic(3+) > tin(2+) > aluminum(3+) > nickel(2+) > selenium(2+) > lithium(1+). [Bansal SK et al; Acta Phramacol Toxicol 53 (4): 333-336 (1983)]**PEER REVIEWED**
  • 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 hr 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 concn; sodium arsenate had similar activity but at concn 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. [Chaineau E et al; Teratology 41 (1): 105-112 (1990)]**PEER REVIEWED**
  • meso-2,3-Dimercaptosuccinic acid, an antidote for the treatment of experimental and human poisoning by a number of heavy metals, has been reported to reduce the lethality of animals poisoned with arsenic more effectively than 2,3-dimercaptopropanol. In the present study, the effect of meso-2,3-dimercaptosuccinic acid on arsenite induced embryotoxic and teratogenic effects was evaluated in mice. In a first experiment, a series of four meso-2,3-dimercaptosuccinic acid injections was administered sc to pregnant Swiss mice immediately after a single ip injection of 12 mg/kg of sodium arsenite given on day 10 of gestation, and at 24, 48, and 72 hr thereafter. meso-2,3-Dimercaptosuccinic acid effectiveness was assessed at dosage levels of 0, 80, 160, and 320 mg/kg/day. Treatment with meso-2,3-dimercaptosuccinic acid significantly reduced the embryolethality and the incidence of gross external and skeletal malformations and variations provoked by sodium arsenite. Based on these findings, the effect of increasing the time interval between acute arsenite exposure and initiation of meso-2,3-dimercaptosuccinic acid therapy wasinvestigated in a second experiment. On day 10 of gestation, meso-2,3-dimercaptosuccinic acid (320 mg/kg) was administered sc to pregnant mice at 0, 0.25, 0.50, 1, 4, or 12 hr after a 12 mg/kg ip dose of sodium arsenite. Embryotoxicity and teratogenicity derived from sodium arsenite exposure were significantly reduced when meso-2,3-dimercaptosuccinic acid was given during the first hour after sodium arsenite injection. According to these results, a delay between acute arsenite intoxication and meso-2,3-dimercaptosuccinic acid treatment should be avoided to have a practical beneficial effect on the arsenite exposed conceptus. [Domingo JL et al; Fundam Appl Toxicol 17 (2): 314-320 (1991)]**PEER REVIEWED**
  • Female Swiss mice were exposed to sodium arsenite or sodium aresenate in the drinking water for 15 wk at concn ranging from 0 to 100 ug/mL arsenic content. After three weeks of the 15 wk exposure period, the mice were administered urethan (1.5 mg/g) ip. Pulmonary adenoma formation was evaluated 12 weeks later. Arsenic exposure produced a protective effect with respect to tumor development. Both forms of arsenic reduced the size and number of pulmonary adenomas observed per mouse. In addition, urethan induced sleeping times which reflect the rate of urethan metabolism or excretion remained unchanged. This suggests that arsenic exposure does not alter urethan excretion and is not a factor influencing subsequent adenoma formation of these levels of exposure. [Blakley BR; Can J Vet Res 51 (2): 240-3 (1987)]**PEER REVIEWED**
  • The acute administration of sodium arsenite (AsIII) to rats resulted in a biphasic alteration of the hepatic cytosolic free heme pool. The first stage was an increase in the cytosolic free heme without significant effects on the content of cytochrome p450 or on bilirubin excretion. The second stage consisted of a continuous fall of the cytosolic free heme and of the content of cytochrome p450. These changes were concurrent with an eight-fold increase in heme oxygenase activity and associated with marked elevations in the biliary excretion of bilirubin. The bile was collected from chronically cannulated rats to avoid artifacts related to anesthesia or post anesthetic effects. The rapid increase in biliary excretion of labeled heme degradation products indicated an increased breakdown of newly synthesized heme. Immunoelectrophoresis of bile proteins showed an altered pattern of bile protein excretion. The increased biliary haptoglobin suggested some hemolysis, while the reduction in the free immunoglobulin A secretory component showed an AsIII-related decreased protein transport across hepatocytes to bile. Further research is required to assess the direct role of an increased heme degradation in the genesis of the hepatotoxic effects of AsIII. [Albores A et al; J Biochem Toxicol 4 (2): 73-8 (1989)]**PEER REVIEWED**
  • Incr in liver zinc and copper concn were noted in rats receiving a single oral dose of 10 mg As/kg as sodium arsenite ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 110 (2000)]**PEER REVIEWED**
  • In a 3-generation study in mice given sodium arsenite in drinking water at an avg dose of 1 mg As/kg/day, there was a singificant incr in the incidence of small litters and a trend toward decr number of pups per litter in all three generations of the treated group ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 117 (2000)]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • Mutation Saccharomyces cerevisiae 100 mmol/l. [NIOSH; Current Awareness Listing (1985)]**PEER REVIEWED**
  • LD50 Rat oral 11.2 ppm. /Arsenite/ [Nat'l Research Council Canada; Effects of Arsenic in the Canadian Environment p.219 (1978) NRCC No. 15391]**PEER REVIEWED**
  • LD50 Rat oral 41 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2947]**PEER REVIEWED**
  • LD50 Rat skin 150 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2947]**PEER REVIEWED**
  • LD50 Mouse ip 1170 ug/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2947]**PEER REVIEWED**
  • LD50 Mouse intramuscular 14 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2947]**PEER REVIEWED**
  • LD50 Rabbit iv 7600 ug/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 2947]**PEER REVIEWED**
  • LD50 Mouse ip 5 mg/kg [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 89 (1980)]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • Arsenite crosses the placenta. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 114 (1980)]**PEER REVIEWED**
  • RATE OF ABSORPTION OF INORG ARSENICALS FROM DIGESTIVE TRACT DEPENDS UPON THEIR SOLUBILITY. SODIUM ARSENITE IS READILY SOL, RAPIDLY ABSORBED. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 35]**PEER REVIEWED**
  • AT 20 HR AFTER IV INJECTION OF 4 MG (76)ARSENIC AS SODIUM ARSENITE TO ONE PATIENT WITH TERMINAL CANCER, HIGHEST LEVELS OF ARSENIC WERE FOUND IN LIVER & KIDNEYS & RELATIVELY SMALLER LEVELS IN VARIOUS OTHER TISSUES. EXCRETION OF (76)ARSENIC IN THE FIRST 24 HOURS AFTER AN IV INJECTION OF LABELLED SODIUM ARSENITE TO 2 PATIENTS WITH TERMINAL CANCER WAS 16.7% OF THE INJECTED DOSE; EXCRETION WAS MAINLY VIA THE URINE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 99 (1980)]**PEER REVIEWED**
  • FOLLOWING IV ADMINISTRATION OF (76)ARSENIC AS SODIUM ARSENITE TO FIVE RATS AND FOUR RABBITS, THE URINARY EXCRETION OF (76)ARSENIC IN THE FIRST 48 HOURS WAS LESS THAN 10% OF THE DOSE IN RATS AND 30% IN RABBITS. FOLLOWING IP INJECTION IN MICE, 75% OF THE DOSE WAS EXCRETED WITHIN THE FIRST 24 HOURS. IN ALL SPECIES TESTED, LESS THAN 10% OF THE TOTAL ... WAS EXCRETED IN THE FECES. UNLIKE RABBITS, RATS RETAIN MOST OF THE INJECTED DOSE IN THE BLOOD FOR A PROLONGED PERIOD. TISSUE DISTRIBUTION STUDIES REVEALED HIGHEST LEVELS OF (76)ARSENIC IN THE BLOOD AND SPLEEN OF RATS, IN THE LIVER, KIDNEYS AND LUNGS OF RABBITS AND IN THE LIVER, KIDNEYS AND SPLEEN OF MICE. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 92 (1980)]**PEER REVIEWED**
  • ... 5 TO 9% OF (74)ARSENIC WAS TAKEN UP BY 8 TERMINAL CANCER PATIENTS FOLLOWING INHALATION OF CIGARETTE SMOKE CONTAINING LABELLED SODIUM ARSENITE. APPROXIMATELY 45% OF THE INHALED ARSENIC WAS EXCRETED IN THE URINE AND 2.5% IN THE FECES AFTER 10 DAYS. AFTER ORAL EXPOSURE TO ARSENITE, OVER 80% OF THE INGESTED DOSE WAS EXCRETED WITHIN 60 HOURS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V23 99 (1980)]**PEER REVIEWED**
  • Hens: Arsenic mainly accumulated in the feathers, but its residues in the muscles, kidneys, liver, and blood exceeded the tolerance limit. Sodium arsenite at 1-5 mg/kg feed inhibited growth and decreased blood hemoglobin, hematocrit, and the SH group content in a concn dependent manner. The As residues decreased in the order: feathers > kidneys > muscles >liver. [Chupakhina OK; Veterinaryia (Moscow) 7: 69 (1983)]**PEER REVIEWED**
  • ... 85% of sodium arsenite applied to crabgrass remained in the leaves after 8 hr. It was suggested that the decreased translocation of the inorganic arsenical may be due to its local toxic effects on foliage. [Nat'l Research Council Canada; Effects of Arsenic in the Canadian Environment p.115 (1978) NRCC No. 15391]**PEER REVIEWED**
  • In an English sheep-dip factory, urinary arsenic levels were determined for workers exposed to mixed arsenic trioxide and sodium arsenite dusts, and for unexposed controls. The urinalysis of exposed personnel were repeated after an interval of 6 months. The mean urinary arsenic level for 54 controls was 0.085 mg As/l, and in 58 determinations made on chemical workers (the most heavily exposed group), the mean was 0.231 mg As/l. The 3 highest levels recorded in the exposed group were equivalent to 0.73, 1.01, and 1.91 mg As/l. Most of the chemical workers (28 of 31) had evidence, in the form of pigmentation and worts, of past systemic arsenicalism. Air samples were collected at a number of locations where chemical workers apparently were employed, and the mean arsenic concn in these areas can be computed as 0.562 mg As/cu m. [Perry K et al; Br J Ind Med 5: 6-15 (1948) as cited in NIOSH; Criteria Document Inorganic Arsenic p.76 (1975) DHEW Pub. NIOSH 75-149]**PEER REVIEWED**
  • The distribution of (74)As-labeled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single iv injections to the mother, the (74)As arsenic appeared to pass the mouse placenta relatively free and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic nell with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithilia of the upper GI tract (oral cavity, esophagus and esophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concn (at 8 hr), both in mother and fetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10 uM), while arsenate seemed to be without effect at concn up to 200 uM. [Lindgren A et al; Acta Pharmacol Toxicol (Copenh) 54 (4): 311-320 (1984)]**PEER REVIEWED**

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Metabolism/Metabolites

  • The urinary metabolites of sodium arsenite have been investigated in rabbits given sodium arsenite and water-soluble dimercaptans. Rabbits injected sc with NaAsO2 (1 mg arsenic/kg) were given im 1 hr later, either saline, 2,3-dimercapto-1-propanesulfonic acid, mesodimercaptosuccinic acid, or N-(2,3-dimercaptopropyl)phthalamidic acid at 0.2 mmol/kg. Arsenic metabolites in urine collected from treated rabbits were isolated by combined anion-cation-exchange chromatography. Column fractions were acid-digested and analyzed for arsenic by direct hydride-flame atomic absorption spectrophotometry. The relative amounts of inorganic arsenic, methylarsonate, and dimethylarsinate found in 0 to 24 hr urine of rabbits given only sodium arsenite agreed closely with those reported for human subjects given arsenite po. This finding suggests that the rabbit biotransforms arsenite in a manner very similar to humans. The urinary excretion of total arsenic between 0 and 24 hr was elevated after dimercaptan administration. but urinary excretion of total arsenic between 0 and 48 hr was unaffected. This result indicates that the action of these dimercaptans occurs early after treatment. In addition, the dimercaptans influenced differently the amounts of the arsenic metabolites excreted in the urine between 0 and 24 hr. 2,3-Dimercapto-1-propanesulfonic acid, mesodimercaptosuccinic acid, or 2,3-dimercapto-1-propanesulfonic acid increased arsenite excretion but decreased dimethylarsinate excretion. 2,3-dimercapto-1-propanesulfonic acid or N-(2,3-dimercaptopropyl)phthalamidic acid treatment increased methylarsonate excretion but mesodimercaptosuccinic acid did not. Arsenate excretion increased after 2,3-dimercapto-1-propanesulfonic acid or mesodimercaptosuccinic acid, treatment but was not affected by N-(2,3-dimercaptopropyl)phthalamidic acid treatment. These results suggest that the dimercaptans, in addition to increasing arsenic excretion, also influence the biotransformation of arsenite to less toxic species. The different effects on the urinary excretion of arsenic metabolites suggest that these dimercaptan metal binding agents have mechanisms of action in addition to simple chelation of inorganic arsenic. [Maiorino RM, Aposhian HV; Toxicol Appl Pharmacol 77 (2): 240-250 (1985)]**PEER REVIEWED**
  • The fungi Candida hemicola biotransforms sodium arsenite to trimethyl arsine. [Cox DP, Alexander M; J Microbiol Ecol 1 (3): 136-144 (1974) as cited in Nat'l Research Council Canada; Effects of Arsenic in the Canadian Environment p.149 (1978) NRCC No. 15391]**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 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**
  • Mice were administered im 1.3 mg As(III)/kg after exposure to a toxic concentration of sodium arsenite (250 mg As(III)/l) for 2, 6 and 8 days. Whereas mice not exposed to the treated drinking water excreted one-half the im administered As(III), those mice previously exposed to the treated water excreted 80% of the applied As(III) as As(V) in 2 days; more than 95%, after 4 days; and after 8 days only traces of As(III) were present ... . [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 34]**PEER REVIEWED**
  • Cultured BALB/3T3-Cl-A31-1-1 mouse embryo cells were used to study the cytotoxicity, neoplastic transformation, and metabolic reduction or oxidation of trivalent arsenic, in the form of sodium arsenite (arsenic(3+)), and pentavalent arsenic, in the form of sodium arsenate (arsenic(5+)). Uptake of arsenic(3+) and arsenic(5+) by the cells was highest during the first hour and was dose dependent; cells treated with equimolar concn of the agents demonstrated four fold greater uptake for arsenic(3+) than for arsenic(5+). Arsenic(3+) was more cytotoxic than arsenic(5+), although no differences were apparent between the two products with respect to total arsenic in the cells. The relative transformation activity for arsenic(3+) compared to arsenic(5+) was equal to about 4:1. Arsenic(5+) showed a high rate of intracellular metabolic reduction; arsenic(5+) exposure yielded more than 70 percent arsenic(3+) in cytosol, as compared to 100 percent for arsenic(3+) exposure. Ion exchange chromatography did not detect any methylated metabolites. In cell free medium incubations, up to 30 percent of arsenic(3+) was oxidized to arsenic(5+), as compared to only 4 percent oxidation in the presence of cells. Unchanged arsenic(5+) was recovered following its incubation in cell free medium, while the presence of cells resulted in the generation of up to 5 percent arsenic(3+), in a dose dependent manner. The reduction of arsenic(5+) to arsenic(3+) by the cells was inhibited up to 25 percent by depletion of glutathione with diethylmaleate. The authors conclude that arsenic(3+) is responsible for the cytotoxic and transforming action of inorganic arsenic. [Bertolero F et al; Carcinogenesis 8 (6): 803-808 (1987)]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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