Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 1327-53-3 Toxicity Effects

Print this page Easy Link

http://ntp.niehs.nih.gov/go/23009

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

Names (NTP)

  • Arsenic trioxide
  • ARSENIC OXIDE (9CI)

Human Toxicity Excerpts

  • ... ARSENIC TRIOXIDE ... KNOWN TO CAUSE SEVERE DAMAGE TO RESP SYSTEM UPON INHALATION. SYMPTOMS INCL COUGH, DYSPNEA, & PAIN IN CHEST. ... ACUTE ... EXPOSURE TO AIRBORNE DUST IS ... ACCOMPANIED BY IRRITATION OF EXPOSED SKIN OR MUCOUS MEMBRANES, EG DERMATITIS, NASAL MUCOSAL IRRITATION, LARYNGITIS, MILD BRONCHITIS, & CONJUNCTIVITIS. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 62]**PEER REVIEWED**
  • MARKED HEPATIC & RENAL DAMAGE HAVE ... BEEN OBSERVED FOLLOWING INGESTION OF ARSENIC TRIOXIDE ... [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 96 (1980)]**PEER REVIEWED**
  • A WOMAN INGESTED APPROX 30 ML OF RAT POISON CONTAINING 1.32% ELEMENTAL ARSENIC AS ARSENIC TRIOXIDE IN 30TH WK OF PREGNANCY. ... ON 4TH DAY AFTER POISONING SHE WAS DELIVERED OF A LIVE INFANT ... WHO DIED 11 HR LATER. ... ARSENIC HAD REACHED FETUS @ EXTREMELY HIGH CONCN. ... CONCN FOUND IN NEWBORN ... ALMOST 150 TIMES REPORTED NORMAL VALUES IN ADULT TISSUES. [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 100 (1980)]**PEER REVIEWED**
  • In an epidemiology study of 8047 white male smelter workers exposed to arsenic trioxide from 1938 to 1963, excess mortality was seen for respiratory cancer, heart disease, cirrhosis of the liver, & tuberculosis. [Lee AM; J Natl Cancer Inst 42: 1045 (1969)]**PEER REVIEWED**
  • In 74 patients taking antihistaminic herbal preparations containing 3.3 mg/day arsenic trioxide, >50% had sensimotor neuropathy. [Tay CH; Med J Aust 2: 424 (1975)]**PEER REVIEWED**
  • CUTANEOUS LESIONS CAN RESULT DURING THE MANUFACTURE OF INSECTICIDES INVOLVING ARSENIC TRIOXIDE. ... PERFORATION OF NASAL SEPTUM HAS OCCURRED AMONG COPPER SMELTER WORKERS. ... PRECEDED BY EPISTASIS, IRRITATION OF NOSE, & CRUST FORMATION WITH OBSTRUCTION TO NASAL BREATHING & NECROSIS OF SEPTUM. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 1522]**PEER REVIEWED**
  • ... PATIENTS WHO USED FOWLER'S SOLN ... INGESTED APPROX 6.69 MG OF ARSENIC AS ARSENIC TRIOXIDE DAILY FOR 9 MO & 3.5 MG DAILY FOR ... 19 MO. INCR FRECKLING & DARKENING OF NIPPLES ... BOUTS OF NAUSEA, CRAMPS, & DIARRHEA. ... REDNESS & PUFFINESS ABOUT ... EYES & PATCHES OF THICKENED SKIN ... HEPATOMEGALY ... NEUROLOGICAL SYMPTOMS. ... [National Research Council. Drinking Water and Health. Volume 3. Washington, DC: National Academy Press, 1980., p. 343]**PEER REVIEWED**
  • Peripherial neurological damage has been observed in persons consuming arsenic-containing antiasthmatic preparations on a long-term basis. Exposure corresponded to 3-10 mg of As/day in the form of As(III)oxide or arsenic sulfide. [WHO; Environ Health Criteria: Arsenic p.142 (1981)]**PEER REVIEWED**
  • A roughly linear relationship was found between cumulative arsenic exposure & lung cancer risk. It is estimated that exposure to airborne arsenic levels about 50 ug/cu m (probably As(III)oxide) for more than 25 yr could result in a nearly 3-fold incr in the incidence of cancer of the respiratory tract after age 65 yr. [WHO; Environ Health Criteria: Arsenic p.18, 21 (1981)]**PEER REVIEWED**
  • IN ... STUDY OF ... WORKERS, EXPOSURE TO ARSENIC TRIOXIDE VAPORS INCR THE INCIDENCE OF CANCER IN THE RESPIRATORY & LYMPHATIC SYSTEMS. [Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978., p. 212]**PEER REVIEWED**
  • To explore the role of arsenic as a human carcinogen, the respiratory cancer mortality experience (1938 to 1977) of 8,045 while male smelter employees in Montana was examined relative to cumulative exposure to arsenic trioxide & was compared with that of the white male population of the same region. Exposure to arsenic was estimated for various work areas from industrial hygiene reports of average concns present in the smelter. Respiratory cancer mortality was analyzed further by time period of first employment & maximum lifetime exposure to arsenic trioxide. When exposure was estimated with arithmetic means of measured concns among men first employed prior to 1925, respiratory cancer mortality increased linearly with increasing cumulative exposure group, ranging from two to nine times of the expected. It also increased linearly with increasing cumulative exposure. [Lee-Feldstein A; J Occup Med 28 (4): 296-302 (1986)]**PEER REVIEWED**
  • ARSENIC TRIOXIDE IS NOT CARCINOGENIC PER SE, BUT REQUIRES A PROMOTER, SUCH AS APPRECIABLE EXPOSURE TO RESPIRATORY IRRITANTS SUCH AS SULFUR DIOXIDE, METAL OXIDE FUMES, OR SMOKING, TO ELICIT THE CARCINOGENIC RESPONSE. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 1522]**PEER REVIEWED**
  • ... TRIVALENT ARSENIC TRIOXIDE ... MORE TOXIC THAN PENTAVALENT ARSENIC OWING TO SLOWER EXCRETION & GREATER RETENTION OF ARSENIC TRIOXIDE IN THE TISSUES. [Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978., p. 209]**PEER REVIEWED**
  • AIRBORNE ARSENIC ... IN FORM OF ARSENIC TRIOXIDE. OVER 23% OF PARTICLES ... IN SAMPLES ... REPORTED TO BE LARGER THAN 5.5 UM. PARTICLES OF THIS NATURE ... UNDERGO HIGH DEPOSITION IN UPPER RESP TRACT. BECAUSE OF DEPOSITION IN NASOPHARYNGEAL REGION & MUCOCILIARY CLEARANCE IN AIRWAYS, MUCH ... MAY BE SWALLOWED & ABSORBED FROM GI TRACT. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 51]**PEER REVIEWED**
  • The ingestion of 9-14 mg of arsenic trioxide by a 16-month infant produced significant signs of poisoning, which required chelation therapy. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1540]**PEER REVIEWED**
  • Investigation of the lethal, UV killing potentiating & repair inhibiting effects of trivalent arsenic trioxide (As203) & pentavalent sodium arsenate (Na2HAsO4) in normal human & xeroderma pigmentosum (XP) fibroblasts. The presence of arsenic trioxide for 24 hr after UV irradiation inhibited the thymine dimer excision from the DNA of normal & xeroderma pigmentosum variant cells thus the subsequent unscheduled DNA synthesis: excision & inhibitions were partial, 30-40, at a physiological dose of 1 ug/ml & 100% at a supralethal dose of 5 ug/ml. Correspondingly, arsenic trioxide also potentiated the lethal effect of UV on excision proficient normal & xeroderma pigmentosum variant cells in a concn dependent manner, but not on excision defective xeroderma pigmentosum group A cells. ... Xeroderma pigmentosum group A & variant strains showed a unique higher sensitivity to arsenic trioxide & pentavalent sodium arsenate killing. [Okui T, Fujiwara Y; Mutat Res 172 (1): 69-76 (1986)]**PEER REVIEWED**
  • A case of angioimmunoblastic lymphadenopathy associated with chronic arsenic ingestion is reported in a 64 yr old asthmatic patient who has been taking Gay's solution arsenic trioxide, combination, digitalis tincture, phenobarbital sodium (sodium phenobarbitone), potassium iodide for 10 yr. Serum arsenic level was 345 mg/l (normal <10). The patient was started on prednisone with improvement of symptoms, including immunoglobulin levels returning to normal. [Offit K, Macris NT; Lancet 1: 1-220 (1985)]**PEER REVIEWED**
  • A recent study on smelter workers reported that arsenic trioxide exposure was associated with coproporphyinuria, but no increases in uroporphyrin excretion nor alterations on the COPRO/URO or COPRO III/ COPRO I ratios were found. [Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 431]**PEER REVIEWED**
  • ... The deleterious effects of arsenic trioxide were principally irritation of exposed body surfaces, skin, conjunctivae, & mucous membranes of the nose which in some cases resulted in perforation of the nasal septum. Of 835 urine determinations of 348 workers, arsenic values raged from 0.1-6.44 mg/l, 95% of which were <2.1 mg/L, resulting in an average of 0.82 mg As/L urine, compared with 0.13 mg/L of 124 unexposed controls. No relation was found between urinary values & severity of the superficial lesions, & moderate cigarette smoking did not incr the amount of arsenic in the urine. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 85]**PEER REVIEWED**
  • A dose of 5-50 mg of arsenic trioxide is toxic. [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 exposed to an estimated time-weighted avg of 0.36 mg As/m3 (as arsenic trioxide) at the Ronnskar copper smelter in Sweden for an avg of 23 yr showed that smelter workers had significantly incr incidences of Raynaud's phenomenon (a peripheral vascular disease characterized by spasm of the digital arteries and numbness of the fingers) and showed incr vasospasticity (constriction of blood vessels) in response to cold when tested in the fingers ... . A follow-up study conducted 2-3 yr later found that vasospasticity measurements ... had improved concurrent with a reduction in arsenic exposure levels, although symptoms of peripheral vascular effects (cold hands or feet, white fingers, numbness in fingers or feet) were still common ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 34 (2000)]**PEER REVIEWED**
  • Dermatitis characterized by hyperpigmentation, folliculitis, and superficial ulcerations was observed in 11 employees in one department of a Malaysian tin smelter (total of 500 employees in the plant) exposed to mean arsenic oxide concn ranging from 0.005 to 0.014 mg As2/O3/m3 (estimated avg exposure = 0.007 mg As/m3) ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 37 (2000)]**PEER REVIEWED**
  • Cross-sectional studies of copper smelter workers at the ASARCO smelter in Tacoma, Washington ... and the Ronnskar smelter in Sweden ... have demonstrated peripheral neurological effects in workers assoc with arsenic trioxide exposure. At the ASARCO smelter, the prevalence of clinically diagnosed peripheral neuropathy was markedly higher in arsenic-exposed workers (26/61 = 43%) than controls (4/33 = 12%), and although the difference in mean nerve conduction velocities (NCV) was not statistically significant, mean peroneal motor NCV was lower in arsenic-exposed workers than controls and all 12 cases of abnormally low NCV occurred in the arsenic group ... . Similar results were observed at the Ronnskar smelter, where ... reported significantly incr prevalence of workers with abnormally low NCV in the exposed group, and lower, but not statistically significant, mean NCV in five peripheral nerves. A follow-up study on the Ronnskar workers 5 yr later found that the prevalence of abnormally low NCV remained significantly incr in the exposed workers, but that the decr in mean NCV was now also statistically significant in the tibial (motor) and sural (sensory) nerves ... . The follow-up Ronnskar study provided enough info to estimate that mean arsenic exposure was 0.31 mg As/m3 and lasted an avg of 28 yr in the exposed group ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 40 (2000)]**PEER REVIEWED**
  • Developmental effects assoc with occupational and environmental exposure to airborne arsenic /as arsenic trioxide/ ... at the Ronnskar copper smelter in northern Sweden ... . In comparison to a northern Swedish reference population, female employees of the smelter had a significantly incr incidence of spontaneous abortion ... and their children had a significantly incr incidence of congenital malformations ... and significantly decr avg birth weight ... Incr incidence of spontaneous abortion and decr avg birth weight of children were also found in populations living in close proximity to the smelter ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 41 (2000)]**PEER REVIEWED**
  • Workers exposed to unspecified concn of arsenic trioxide at the Ronnskar copper smelter in Sweden were found to have a significant incr in the frequency of chromosomal aberrations in peripheral lymphocytes ... . [DHHS/ATSDR; Toxicological Profile for Arsenic p. 43 (2000)]**PEER REVIEWED**
  • Respiratory cancer in smelter workers exposed to arsenic trioxide may be promoted by concurrent exposures to respiratory irritants such as SO2, silica, & "other" metals. [ACGIH Documentation of the Threshold Limit Values 4th ED p.26 (1980)]**PEER REVIEWED**

Back to Top

Non-Human Toxicity Excerpts

  • ... Applied to rabbit eyes causes discomfort, edema of lids, corneal injury, and opacity, and when placed in anterior chamber has local necritizing action. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 117]**PEER REVIEWED**
  • GASTROINTESTINAL DAMAGE, AS EVIDENCED BY SEVERE CONVULSIONS & RETCHING, & HEMORRHAGE OF STOMACH & INTESTINES WAS A MARKED FEATURE OF CRUDE ARSENIC TRIOXIDE, WHILE THE PURE PREPARATION CAUSED MUCH LESS DISCOMFORT & ONLY SLIGHT REDDENING OF GASTRIC MUCOSA. [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 43]**PEER REVIEWED**
  • NO EXCESS OF TUMORS COMPARED WITH CONTROLS WAS SEEN IN 50 C57BL MICE RECEIVING ARSENIC TRIOXIDE IN ... DRINKING-WATER AS 0.0004% SOLN OF 12% AQ ETHANOL FROM AGE 2 MO FOR 15 MO ... HIGHER DOSES WERE LETHAL. ... 77 SWISS MICE RECEIVED 0.01% ... IN THEIR DRINKING-WATER; TUMOR INCIDENCE IN ... MICE SURVIVING ... WAS SIMILAR TO CONTROLS. [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 83 (1980)]**PEER REVIEWED**
  • ... WISTAR KING RATS, 10 WK OLD, RECEIVED 0.2 ML OF AQ SOLN CONTAINING 1 MG/ML ARSENIC TRIOXIDE INTRATRACHEALLY ONCE A WK FOR 4 MO (15 DOSES) ... CONTROL RATS WERE TREATED WITH SALINE. ... 1 OF TREATED ANIMALS DEVELOPED A LUNG ADENOMA & 4 HAD METAPLASIA &/OR OSTEOMETAPLASIA OF ALVEOLAR CELLS OR OF AIRWAY EPITHELIAL CELLS. /RESULTS FOR CONTROLS NOT GIVEN IN TEXT/ [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 87 (1980)]**PEER REVIEWED**
  • RATS GIVEN 10 MG/KG/DAY ARSENIC TRIOXIDE BY STOMACH TUBE FOR 40 DAYS SHOWED HAIR LOSS ... ECZEMA, HYPERPLASIA & HYPERKERATOSIS OF SKIN. CLINICAL SYMPTOMS OF BLEEDING, ULCERATION & CRUST FORMATION OCCURRED IN SOME CASES. ORAL ADMIN OF 0.125-62.5 MG/L ... TO RATS PRODUCED ... PROLIFERATION IN BILE DUCT, WITH CHRONIC ANGIITIS. [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**
  • THE OFFSPRING OF FEMALE RATS FED A DIET CONTAINING 100 PPM ARSENIC TRIOXIDE DURING PREGNANCY AND THROUGHOUT THE SUCKLING PERIOD SHOWED NO EFFECTS ON HARD TISSUE. [KOJIMA H; NIPPON YAKURIGAKU ZASSHI 70 (2): 149 (1974)]**PEER REVIEWED**
  • MICE WERE ADAPTED TO 12.5 DEG C, 22.5 DEG C (ROOM TEMP), AND 32.5 DEG C, WITH AND WITHOUT CHRONIC INTRAPERITONEAL ARSENIC TRIOXIDE. ARSENIC INCREASED MITOCHONDRIAL RESPIRATION AT ROOM TEMP, BUT DECREASED IT IN HOT- AND COLD-ADAPTED MICE. AT ROOM TEMP IT INCREASED HEART AND LIVER PYRUVATE KINASE AND DECREASED ENZYME ACTIVITIES IN OTHER ORGANS. ADAPTATION TO COLD MODIFIES THE TOXIC EFFECTS OF ARSENIC TRIOXIDE ON RESPIRATION AND GLYCOLYSIS. [MALASEK A, LOCKER A; VERH DTSCH ZOOL GES 67: 250 (1975)]**PEER REVIEWED**
  • ARSENIC TRIOXIDE (2-120 MG/KG, ORALLY) INCREASED ERYTHROCYTE OSMOTIC FRAGILITY IN RATS. [TSUZUKI S ET AL; MATSUMOTO SHIGAKU 6 (2): 173 (1980)]**PEER REVIEWED**
  • Chronic exposure to arsenic trioxide caused deterioration of the germinative epithelium of the testis in hairless mice. [Bencko V; Cesk Hyg 13: 344 (1968)]**PEER REVIEWED**
  • The most sensitive species to arsenic trioxide are chironomid larvae, mayfly nymphs, and fresh water shrimp at 2.5 to 4 ppm. [Surber EW, Meehean OL; Trans Am Fish Soc 61: 225 (1931) as cited in USEPA; Ambient Water Quality Criteria Doc: Arsenic p.B-23 (1980) EPA 440/5-80-021]**PEER REVIEWED**
  • Nearly 6,000 cattle were accidentally given feed for 1-2 days containing As(III) oxide at levels between 490 and 2900 mg/kg. Deaths occurred after 3 days. More than 50% of the 1464 animal deaths took place during the first week following the administration of the feed. Symptoms included: drastic reduction in milk production, diarrhea, dehydration, dyspnea, cyanosis, abortion, and CNS effects. Chronic effects included: hyperkeratosis of skin, rigidity and inflammation of joints, and blindness with corneal opacities. [Gonzalez SG; Memorias Deli Simposium Internat de Laboratorios Veteiarios de Diagnosticos, Mexico 3: 551-60 (1977)]**PEER REVIEWED**
  • Arsenic trioxide administered to Western spruce budworm (Choristoneura occidentalis) at dietary levels of 99.5 mg/kg killed 10%, 2,550 mg/kg killed 50%, and 65,300 mg/kg was fatal to 90%. Newly molted purae and adults of As exposed larvae had reduced weight. [Robertson JL, McLean JA; J Econ Entomol 78: 1035-6 (1985) as cited in Arsenic Hazards to Fish, Wildlife, and Invertebrates: A synoptic review, Report No 12 p.42 (1988)]**PEER REVIEWED**
  • Experiments with grazing cows and cows kept indoors were performed to study the transfer of toxic elements from their ration into milk and edible tissues. ... One group received cadmium, lead and mercury acetate, and arsenic trioxide. The dosing period lasted 28 months or 3 consecutive complete lactations. Liver and in particular kidney were the primary sites of element accumulation. Only for cadmium the proposed tolerance levels in liver and kidney were exceeded. Increased dietary concentrations of elements did not result in significantly higher concentrations in milk, blood and muscle tissue. Only soluble arsenic resulted in higher levels of this element in muscle tissue. Regarding the character of the pathological changes, no essential differences were observed between the control and experimental groups. [Vreman K et al; Neth J Agric Sci 34 (2): 129-44 (1986)]**PEER REVIEWED**
  • Male Syrian golden hamsters were given arsenic trioxide, calcium arsenate, or arsenic trisulfide by intratracheal instillation once a week for 15 weeks; the total dose was 3.75 mg arsenic. The animals were maintained for lifespan observation. Sixty percent of the hamsters given arsenic trioxide, 90 percent given calcium arsenate, and 77 percent given arsenic trisulfide died. The major cause of death was pneumonitis resulting from arsenic toxicity. The differences in tumorigenesis rate in the arsenic trioxide and arsenic trisulfide groups and the controls were not significant; however, the rate of tumor formation in the calcium arsenate group was significant. [Yamamoto A et al; Int l J of Cancer 40 (2): 220-23 (1987)]**PEER REVIEWED**
  • The effects of single and multiple 3 hour inhalation exposures to aerosols of arsenic trioxide on the pulmonary antibacterial defense system were studied in mice. Female CD1 mice, ages 4 to 5 weeks, were exposed to arsenic trioxide mists or filtered air (controls) in a concentration range from 125 to 1,000 ug/cu m arsenic (As). The mice were challenged with an aerosol of Streptococci, and pulmonary bacterial activity of alveolar macrophages was assessed by exposure to aerosols of labeled Klebsiella pneumoniae. Significant increases in mortality due to bacterial exposure and decreases in bacterial activity were observed after single 3 hour exposures to 271, 496, and 940 ug/cu m As. There was a significant positive linear relationship of increased mortality with increased As concentration. Inhalation of 500 ug/cu m and above produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity after 1, 5, or 20 exposures. [Aranyi C et al; J Toxicol Environ Health 15 (1): 163-72 (1985)]**PEER REVIEWED**
  • The effect of arsenic and mercury on the frequency of chromosomal aberrations induced by ethylmethane sulfonate was studied in male outbred Swiss albino mice. Some mice were injected intraperitoneally (ip) with 12 mg/kg arsenic trioxide or 6 mg/kg mercuric chloride. Ethylmethane sulfonate was injected ip at a dose of 200 mg/kg either alone or 20 minutes after injection of one of the other compounds. Other mice received either distilled water (negative controls) or mitomycin-C injections (positive controls). Animals were sacrificed after recovery periods of 12, 24, 36, and 48 hours. Cytogenetic damage was evaluated by determining the frequency of gaps, breaks, and exchanges in bone marrow and in spermatogonia. Neither arsenic nor mercury alone induced an increased gaps, breaks, and exchanges in the cells examined. Ethylmethane sulfonte alone increased gaps in bone marrow cells but produced no other damaging effects. In the combined treatments, neither arsenic nor mercury affected the frequency of gaps, breaks, or exchanges induced by ethylmethane sulfonate alone. Acute arsenic and mercury do not enhance the chromosomal aberrations induced by ethylmethane sulfonate in either the bone marrow cells or spermatogonia of mice. [Poma K et al; J Appl Toxicol 4 (6): 293-6 (1984)]**PEER REVIEWED**
  • Young adult rats were exposed via inhalation or intratracheal instillation to oxides of arsenic, beryllium, cadmium, cobalt, lead, selenium, vanadium, and ytterbium. Serial necropsies were performed to assess the metal content in organs at times up to several weeks after exposure. The lung clearance varied widely for these compounds, and the times to remove 50% of the initial burden ranged from 18 min for vanadium to 400 days for beryllium. Arsenic, cadmium, lead, selenium, and vanadium were initially soluble in lung, but a small fraction (1-20%) remained there over the long term. Extrapulmonary tissues often accumulated substantial amounts of the soluble oxides, and whole body retention was often greater for compounds that were more soluble in lung. Arsenic, selenium, and vanadium translocated to carcass and bone. Arsenic, cadmium, lead, and selenium accumulated in the liver, and the kidney retained cadmium and lead. Beryllium, cobalt and ytterbium did not deposit at any extrapulmonary site in significant amounts. In general, the aqueous solubility of these compounds was a poor predictor for behavior in vivo. Of the metal oxides tested for acute lethality following pulmonary deposition, cadmium was most toxic, followed by selenium, vanadium, and arsenic. [Rhoads K, Sanders CL; Environ Res 36 (2): 359-78 (1985)]**PEER REVIEWED**
  • The relative toxicity of gallium arsenide and its metal oxides was assessed by intratracheally instilling particulate suspensions of gallium arsenide (100 mg/kg), equimolar gallium as gallium trioxide (655 mg/kg), or a maximally tolerated nonlethal dose of arsenic as arsenic trioxide (17 mg/kg). Two weeks after dosing, rats were selected for the biochemical determination of lung lipid, protein, DNA, and collagen (4-hydroxyproline; 4-HP) content. The pulmonary retention of gallium and/or arsenic and the concentration of these metals in blood were also determined. Pulmonary exposure to gallium trioxide particulates significantly (p < 0.55) increased the total lipid content of lungs. This response appeared to be associated with the pulmonary retention of gallium particulates (means= 36% of the gallium dose). In contrast, arsenic trioxide particulates were not retained in the lung. Blood arsenic concentrations were 36 ppm which represented 20% of the total arsenic administered. Treatment with arsenic trioxide significantly elevated lung dry weight as well as protein, DNA, and 4-HP content. Arsenic trioxide induced an acute fibrogenic response. The intratracheal instillation of gallium arsenide particulates produced effects similar to those observed with the individual oxides. The total lung content of lipids, protein, and DNA was significantly elevated. These biochemical changes were accompanied by significant increases in lung dry weight and lung wet weight. Lungs from rats receiving gallium arsenide particulates retained 44% of the dose as gallium and 28% of the dose as arsenic at the end of the 14 day study. Blood arsenic concentrations were 44 ppm (7% of the arsenic dose) while gallium was not detected in blood at this time. The primary histopathological observations 14 days after the intratracheal instillation of all metal particulates were an inflammatory respponse and pneumonocyte hyperplasia. The biological serverity of these lesions, in descending order, was gallium arsenide greater than arsenic trioxide much greater than gallium trioxide. [Webb DR et al; Toxicol Appl Pharmacol 82 (3): 405-16 (1986)]**PEER REVIEWED**
  • Arsenic trioxide, with a carrier dust charcoal C, and H2S04 were intratracheally instilled into male hamsters at approx 3, 40, and 0.4 mg/kg, respectively. Macroscopic exam was done on the larynx, trachea, bronchi, and lung, and on other tissues in animals which died after the 15 wk exposure period. Among 47 arsenic treated animals, 3 pulmonary carcinomas were found. [Pershagen G et al; Arch Toxicol 7: 403-4 (1984)]**PEER REVIEWED**
  • Juvenile rainbow trout were fed semipurified diets in 8 wk growth trials to compare the toxicity of 4 dietary arsenicals: arsenic trioxide, disodium arsenate heptahydrate (DSA), dimethylarsinic acid (DMA), and arsanilic acid (AA). Toxicity responses of reduced growth and feed consumption, and altered feeding behavior, were noted at all levels of supplementation of arsenic trioxide and disodium arsenate heptahydrate (137-1477) ug As/g diet). In contrast, even at the highest levels of supplementation (1497 ug As/g diet as dimethylarsinic acid, and 1503 ug As/g diet as arsanilic acid the organic arsenicals did not result in these toxicity signs. Carcass As concn showed a dose response relationship to dietary As concn, whereas at higher levels, dietary arsenic trioxide yielded the highest residues. The no observed effect concn for dietary arsenic trioxide lies between 1 and 137 ug As/g diet for disodium arsenate heptahydrate, between 1 and 180 ug As/g diet for arsenic trioxide, and is at least 1497 ug As/g diet for dimethylarsinic acid and arsanilic acid. [Cockell KA, Hilton JW; Aquat Toxicol 12 (1): 73-82 (1988)]**PEER REVIEWED**
  • The effects of 6 months exposure to arsenic trioxide in fresh water on the parr-smolt transformation of coho salmon were evaluated. Exposure to 300 ug As/l arsenic trioxide appeared to delay the onset of the normal increase in plasma thyroxine concn and cause a transient reduction of gill Na+, K+ dependent ATPas activity. Fish exposed to 300 ug As/l also migrated to the sea less successfully than did nonexposed smolts, but there were no effects on the survival and growth of smolts held in 28% salt water for 6 months. [Nichlos JW et al; Environ Toxicol Chem 3 (1): 143-9 (1984)]**PEER REVIEWED**
  • ... Arsenic inhibits the excision of pyrimidine dimers. Partially repair suppressing small doses of arsenic trioxide (0.5 ug/ml) and pentavalent sodium arsenate (5 ug/ml) enhanced co-mutagenically the UV induction of 6-thioguanine-resistant mutations of V79 Chinese hamster cells. [Okui T, Fujiwara Y; Mutat Res 172 (1): 69-76 (1986)]**PEER REVIEWED**
  • Pregnant CFLP mice were exposed to 0.26, 2.9, or 28.5 mg/cu m arsenic trioxide by inhalation for 4 hours daily on days 9 through 12 of gestation. On day 18, the fetuses were removed and assayed for mortality, growth retardation, skeletal malformations, and structural chromosomal aberrations in liver cells. Exposure to 28.5 mg/cu m arsenic significantly reduced the number of live fetuses, average fetal weight, and significantly increased the number of fetuses with retarded growth. The 0.26 and 2.9 mg/cu m doses significantly reduced average fetal weight and insignificantly increased the number of dead fetuses. The 28.5 mg/cu m dose significantly increased the incidence of skeletal malformations. Retarded ossification of the limbs was the most frequently observed malformation. Arsenic trioxide at 28.5 mg/cu m significantly increased the incidence of chromosomal aberrations. The frequency of chromosomal aberrations was slightly, but not significantly, elevated in animals given the 0.26 and 2.9 mg/cu m exposures. [Nagymajtenyi L et al; J Appl Toxicol 5 (2): 61-3 (1985)]**PEER REVIEWED**
  • Cattle (Bos spp) single oral dose of 15 to 45 grams/animal fatal. [Effects of Arsenic in the Canadian Environment Natl Res Coun Canada Publ No NRCC 15391 1-349 (1978) as cited in Arsenic Hazards to Fish, Wildlife, and Invertebrates: A Synoptic Review, Report No 12 p.62 (1988)]**PEER REVIEWED**
  • Single exposures of mice to arsenic trioxide (0.94 mg/cu m As) led to increased susceptibility to respiratory bacterial pathogens, apparently as a result of injury to alveolar macrophages. [Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 431]**PEER REVIEWED**
  • The only report of a lethal effect of inhaled inorganic arsenic in animals was a developmental toxicity study in which four of nine pregnant rats died, and one rat was euthanized in extremis, between days 12 and 19 of gestation after 30-35 days of exposure to an aerosol of aersenic trioxide at an exposure concn of 20 mg As/cu m ... . These animals exhibited severe hyperemia and plasma discharge into the intestinal lumen at autopsy. ... there was 100% mortality in groups of 10 pregnant rats after 1 day of exposure to concn 100 mg/cu m (76 mg As/cu m). [DHHS/ATSDR; Toxicological Profile for Arsenic p. 19 (2000)]**PEER REVIEWED**
  • Pregnant female rats exposed to arsenic trioxide dust starting 14 days prior to mating and continuing through mating and gestation exhibited rales at 8 mg As/m3 and labored breathing and gasping at 20 mgAs/m3, with no symptoms at 2 mg As/m3 ... . The lungs were examined by gross necropsy and no lesions were found. [DHHS/ATSDR; Toxicological Profile for Arsenic p. 33 (2000)]**PEER REVIEWED**

Back to Top

Human Toxicity Values

  • None found

Back to Top

Non-Human Toxicity Values

  • LD50 Mice (several strains) gavage 26-47 mg/kg [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 82]**PEER REVIEWED**
  • LD50 Rat gavage 15 mg/kg [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 82]**PEER REVIEWED**
  • LD50 Rat oral (in food) 145 mg/kg [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 82]**PEER REVIEWED**
  • LD50 Rat ip 871 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. 278]**PEER REVIEWED**
  • LD50 Mouse oral 31,500 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. 278]**PEER REVIEWED**
  • LD50 Mouse sc 9800 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. 278]**PEER REVIEWED**
  • LD50 Mouse iv 10,700 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. 278]**PEER REVIEWED**
  • LD50 Swiss mice (male; 20-25 g) oral 42.9 +/- 2.1 mg/kg (97.8% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Swiss mice (male; 20-25 g) oral 39.4 +/- 4.7 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Swiss mice (male; 35-40 g) oral 47.6 +/- 3.3 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 C57H16 mice (male) oral 25.8 +/- 1.8 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Dba2 Mouse (male) oral 32.4 +/- 2.3 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 C3H Mouse (male) oral 25.8 +/- 1.8 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Sprague-Dawley rat (male; 125-200 g) oral 23.6 +/- 1.4 mg/kg (97.8% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Sprague-Dawley rat (male; 125-200 g) oral 15.1 +/- 1.8 mg/kg (99.999% solution) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Sprague-Dawley rat (male; 125-200 g) oral 214.0 +/- 8.4 mg/kg (97.8% dry) /From table/ [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. 546]**PEER REVIEWED**
  • LD50 Sprague-Dawley rat (male; 125-200 g) oral 145.2 +/- 8.7 mg/kg (99.999% dry) /From table/ [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. 546]**PEER REVIEWED**

Back to Top

Absorption, Distribution and Excretion

  • BOTH HUMAN & ANIMAL DATA INDICATE THAT OVER 80% OF INGESTED DOSE OF DISSOLVED INORG TRIVALENT ARSENIC IS ABSORBED FROM GI TRACT. ... IN CASE OF ARSENIC TRIOXIDE, WHICH IS ONLY SLIGHTLY SOL IN WATER, GI ABSORPTION WILL BE DEPENDENT ON FACTORS SUCH AS PARTICLE SIZE & PH OF THE GASTRIC JUICES. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 51]**PEER REVIEWED**
  • FOLLOWING DIETARY ADMIN OF 215 PPM ARSENIC IN FORM OF ... ARSENIC TRIOXIDE FOR UP TO 52 DAYS IN RATS, HIGHEST ... LEVELS ... WERE FOUND IN KIDNEYS & LIVER & RELATIVELY LOWER LEVELS IN HAIR, BRAIN, BONE, MUSCLE & SKIN. ... TRIVALENT ARSENIC ... IS CONVERTED TO ... /PENTAVALENT ARSENIC IN MAN/ WHICH IS RAPIDLY EXCRETED BY KIDNEYS. [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**
  • ORAL ADMIN OF 1 MG/KG BODY WT ARSENIC AS ARSENIC TRIOXIDE TO MONKEYS RESULTED IN APPROXIMATELY 80% ABSORPTION FROM THE GUT; 75% OF THE ADMIN DOSE WAS EXCRETED WITHIN 14 DAYS, PRIMARILY IN 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 91 (1980)]**PEER REVIEWED**
  • ... MALE & ... FEMALE RATS, 21 DAYS OF AGE WERE GIVEN DIET CONTAINING 26.8 OR 215 MG/KG OF DIET ARSENIC AS ARSENIC TRIOXIDE AD LIBITUM. ... LITTERS OF FOLLOWING 3 PREGNANCIES WERE EVALUATED, AS WELL AS FIRST LITTER OF SECOND GENERATION. AMT ... FOUND IN NEWBORNS WAS LOWER IN FIRST LITTER OF FIRST GENERATION ... THAN LATER LITTERS ... [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**
  • ARSENIC TRIOXIDE (5-10 MG/KG) WAS ADMINISTERED ORALLY TO WISTAR RATS DURING DAYS 0-20 OF GESTATION. FETUSES REMOVED ON THE 21ST DAY ... /LIVER, BRAIN AND WHOLE ORGAN ARSENIC CONCN WERE MEASURED/. [TAMURA S, TANAKA I; JPN J PHARMACOL 25 (SUPPL): 133 (1975)]**PEER REVIEWED**
  • IN A FACTORY (PRODUCING ARSENIC ACID AS A WOOD PRESERVATIVE) WHERE ARSENIOUS ACID IS OXIDIZED, THE CONTENT OF ARSENIC IN FACTORY AIR WAS 0.015 AND 0.03 MG/CU M. THE ARSENIC CONTENT OF WORKER SCALP HAIR WAS 26-348 PPM; AXILLAR HAIR WAS 54-235 PPM, COMPARED TO CONTROL AVERAGE OF 0.26 PPM. AVERAGE WORKER BLOOD ARSENIC CONTENT WAS 3.3 UG/100 G COMPARED TO CONTROL VALUES OF 0.7 UG/100 G. AVERAGE WORKER URINE ARSENIC CONTENT WAS 169 UG/L, COMPARED TO 78 UG/L IN CONTROLS. [YAMAMURA Y, YAMAUCHI H; SANGYO IGAKU (JPN J INDUSTRIAL HEALTH) 18 (2): 530 (1976)]**PEER REVIEWED**
  • Animal data have shown substantial differences in lung retention after intratracheal instillations of arsenic trisulfide, calcium arsenate & arsenic trioxide. Retention of ... arsenic trisulfide was 10 times higher compared to arsenic trioxide. [National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 279]**PEER REVIEWED**
  • ... In workers exposed to arsenic trioxide, inorganic arsenic, monomethylarsonic acid & dimethylarsinic acid are the only chemical forms of As excreted in the urine that are relevant to a study of occupational exposure. Blood As concn is proportional to exposure & correlates only with urinary dimethylarsinic acid excretion; dimethylarsinic acid seems to be the most appropriate single indicator of exposure. At high levels of exposure (total As excretion above 200 ug/l), As accumulates in the organism & dimethylarsinic acid excretion reflects its accumulation. At low levels of exposure (total As excretion below 50 ug/l) a short-term accumulation does not occur & the best biological indicator of exposure is inorganic arsenic exretion. Seafood ingestion brings about a marked incr in urinary excretion of total As that lasts for 24-48 hr & is not accompanied by any incr in inorganic arsenic, monomethylarsonic acid or dimethylarsinic acid excretion. Organic As from seafood does not mix with the pool of inorganic As in the organism & may be separately detected in urine. In the biological monitoring of human exposure to As, particularly in the case of high urinary values, the speciation of the chemical forms of As in urine is necessary in order to establish with certainty the source, industrial or alimentary, of exposure. [Foa V et al; Sci Total Environ 34 (3): 241-59 (1984)]**PEER REVIEWED**
  • Lung retention of antimony & arsenic in neutron activated dust was studied in hamsters. Male Syrian gold hamsters were administered dust from a Swedish copper smelter by intratracheal instillation. The dust was known to contain 1.6 weight % antimony & 19 weight % arsenic. The calculated doses were 1.46 mg/kg arsenic & 0.04 mg/kg antimony. The rate of lung clearance for the radionuclide arsenic-76 was monitored for 43 hr & that of antimony-124 for 190 hours. Aerosols of radiolabeled arsenic trioxide & antimony trioxide were also instilled. Lung clearance was biphasic. The biological half-times in hrs for the initial phase were: arsenic trioxide, 13; arsenic in dust, 20; antimony trioxide, about 40; & antimony in dust, 30. The half-times of the second phase of clearance were 20-40 hr for both antimony trioxide & antimony. Because of the short physical half-life of arsenic-76, 26.5 hr, it was not possible to follow the second phase of lung clearance for arsenic dust & arsenic trioxide. [Leffler P et al; Scand J Work Environ Health 10 (4): 245-51 (1984)]**PEER REVIEWED**
  • Urine concns of inorganic arsenic metabolites were determined in 99 randomly selected subjects without known exposure to arsenic & in 20 male workers exposed to arsenic trioxide at a nonferrous smelter in northern Sweden. A skewed distribution was found. Among unexposed subjects, the geometric mean was 8.2 ug/As/g creatinine. The arithmetic mean was about 30% higher. Urinary concns of inorganic arsenic were independent of sex, place of residence, smoking habits, & consumption of beer or wine. Levels were 1.5 times higher in subjects who frequently ate flatfish & crustacea. Dimethylarsinic acid (DMA) was the only metabolite which correlated with total metabolite concn, indicating that it accounted for most of the variation of inorganic arsenic. In subjects occupationally exposed, urinary concn of inorganic arsenic increased during the first day of exposure, & then leveled off, indicating a steady state, between exposure & excretion. During steady state 19% of urinary arsenic was inorganic arsenic, 20% was methylarsonic acid, & 61% was dimethylarsinic acid, which was similar to the distribution of urinary metabolites among the general population. After 2 days free from work, as much as 80% of the urinary arsenic metabolites were in the form of dimethylarsinic acid. All 3 metabolites were significantly correlated with total urinary metabolites. [Vahter M; Acta Pharm Toxicol 59: 31-4 (1986)]**PEER REVIEWED**
  • The relationship between airborne concns of arsenic & the urinary excretion of inorganic arsenic metabolites (inorganic arsenic + methylarsonic acid + dimethylarsinic acid) was studied among smelter workers exposed to arsenic trioxide. The urinary concns of arsenic metabolites increased steadily during the first day of the working week (after 2-3 days off from work), after which they reached a steady state. The concn in the late evening after a day of exposure wass very similar to that in the early morning of the following day. Both were well correlated with the total daily excretion. In a second part of the study the first-void morning urine was collected for 2-3 days during the steady state phase. Arsenic in the breathing zones was measured by personal air samplers. There was a good correlation between the concn of metabolites of inorganic arsenic in urine & the concn of airborne arsenic in the form of arsenic trioxide. ... Airborne arsenic varied between 1 & 194 ug/cu m, while urinary arsenic ranged between 16 & 328 ug/cu m. [Vahter M et al; Intl Arch Occup Environ Health 57 (2): 79-91 (1986)]**PEER REVIEWED**
  • A single dose of arsenic trioxide administered to hamsters was chiefly methylated in vivo into methylarsonic acid & dimethylarsinic acid (DMAA); inorganic As accounted for the major portion of total As that deposited in organs & tissues, followed by methylarsonic acid & dimethylarsinic acid in decreasing order. The single oral dose of arsenic trioxide was followed by a very small amt of trimethylarsenic occurring only in the liver. The distribution pattern of As in the blood following the single oral dose of arsenic trioxide was such that inorganic As & methylarsonic acid occurred chiefly in the blood cells; dimethylarsinic acid, chiefly in the plasma; the As cmpd disappeared rapidly from blood. The single oral dose of arsenic trioxide was further followed by excretion of an amt of As equiv to approx 60% of the administered dose: 49% in the urine & 11% in the feces. Dimethylarsinic acid accounted for the major portion of As excreted in the urine & feces, & this finding reconfirmed that dimethylarsinic acid is the major metabolite. [Yamauchi, Yamamura Y; Toxicol 34 (2): 113-21 (1985)]**PEER REVIEWED**
  • Tissue analysis of organs taken from an individual following death from ingestion of 8g of arsenic trioxide (about 3g of arsenic) showed a much higher concn of arsenic in liver (147 ug/g) than in kidney (27 ug/g) or muscle, heart, spleen, pancreas, lungs, or cerebellum (11-12 ug/g) ... . Small amt were also found in other parts of the brain (8 ug/g), skin (3 ug/g), & hemolyzed blood (0.4 ug/g). [DHHS/ATSDR; Toxicological Profile for Arsenic p. 137 (2000)]**PEER REVIEWED**
  • The nature of the daily diet may effect the enteric absorption of arsenic. Arsenic(III)oxide added to a milk diet (80% whole milk powder & 20% dextrin) was eliminated with the feces of rats in greater amounts, after several weeks of feeding, than the same substance added to a cereal diet. When the cereal diet of rats was supplemented with casein (20%), in addition to As(III)oxide, the feces contents of arsenic were higher than after supplementation with cheese, butter, or whey powder. No differences in the fecal elimination of arsenic were noted in rats fed arsenic together with cereal & cereal supplemented with 20% egg albumin, lactalbumin, polypeptone, or polyamine, or with 1% methionine, taurine, or cysteine ... . [WHO; Environ Health Criteria 18: Arsenic p.53 (1981)]**PEER REVIEWED**
  • Trivalent arsenic in the form of arsenic(III)oxide, suspended in a gum soln was administered to rabbits & rats in single doses of 22 mg of arsenic/kg bw. The recovery of arsenic in the feces in the 4 days following dosing was 59% for the rabbits & 69% for the rats. Arsenic(III)oxide dissolved in water & mixed in the food was admin to rats ... . Of the calculated avg intake of arsenic (0.37 mg), only about 14% was eliminated with feces during the first 3 days. The results of these 2 studies indicate that dissolved arsenic(III)oxide is more rapidly absorbed than undissolved arsenic(III)oxide. ... [WHO; Environ Health Criteria 18: Arsenic p.52 (1981)]**PEER REVIEWED**

Back to Top

Metabolism/Metabolites

  • CHEMICAL SPECIATION STUDIES HAVE SHOWN THAT DIMETHYLARSINIC ACID & METHANEARSONIC ACID ARE PRIMARY FORMS OF ARSENIC PRESENT IN URINE OF HUMANS EXPOSED TO ... ARSENIC TRIOXIDE BY INHALATION. [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 100 (1980)]**PEER REVIEWED**
  • Urinary profiles of arsenic smelter workers showed that dimethylarsenic acid was the major species followed by methyl arsenic, trivalent arsenic, and pentavalent arsenic. [Smith TJ; Envir Health Perspect 19: 89 (1977)]**PEER REVIEWED**
  • Urinary concentrations of the four arsenic species, pentavalent (As(V)) and trivalent (As(III)) inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide and sodium orthoarsenate, respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/1. The increasing predominance of the less toxic methylated species, especially dimethylarsinic acid, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V), As(III), monomethylarsonic acid and dimethylarsinic acid in both cases probably reflect species dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation. [Lovell MA, Farmer JG; Hum Toxicol 4 (2): 203-14 (1985)]**PEER REVIEWED**
  • Rat liver cytosol inactivates inorganic arsenic through methylation; S-adenosylmethionine is the methyl group donor and reduced glutathione is required for full activity. ... Pathway involves the formation of a monomethylated metabolite which is either rapidly further methylated into a dimethylated derivative or is spontaneously oxidized into monomethylarsinic acid. The dimethylated metabolite gives rise to dimethylarsinic acid. The first methylation reaction is rate limiting, can be stimulated by glutathione and is catalyzed by an enzyme different from that which transfers the second methyl group. The latter is sensitive to inhibition by inorganic arsenic. ... A large excess of thiol groups may prevent the methylation reactions probably by decreasing the amount of free trivalent arsenic. [Buchet JP, Lauwerys R; Biochem Pharm 37 (16): 3149-53 (1988)]**PEER REVIEWED**

Back to Top

TSCA Test Submissions

  • None found

Back to Top

Footnotes

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

Back to top

Web page last updated on May 14, 2008