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Some Results of a Physiologically Based Pharmacokinetic Modeling Approach to Estimating Arsenic Body Burdens

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Arsenic

Abstract

Arsenic occurs widely in drinking-water throughout the US and most other parts of the world because of its wide distribution in the earth’s crust. In Taiwan, consumption of arsenic in drinking-water was associated with a vascular blood return defect, blackfoot disease (Astrup, 1968; Ch’i and Blackwell, 1968; Yu et al., 1984; Yu, 1984). Subsequent studies found an association between arsenic drinking-water levels and skin cancer (Tseng et al., 1968; Yeh, 1973; Bates et al., 1992; Chen et al., 1992; Smith et al., 1992) and other cancers (Tseng et al., 1968; Yeh, 1973; Bates et al., 1992; Chen et al., 1992; Smith et al., 1992). On the basis of these reports, US EPA calculated an arsenic cancer risk on the assumption that all forms of arsenic were equivalent in cancer potency and that all ingested arsenic was retained in the body over a lifetime. This approach is highly conservative, but could lead to inappropriate public policy for arsenic regulation if it were erroneous.

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References

  • Agahian, B., Lee, J.S., Nelson, J.H. and Johns, R.E. (1990) Arsenic levels in fingernails as a biological indicator of exposure to arsenic. Am. Ind. Hyg. Assoc. J., 51, 646–51.

    Article  Google Scholar 

  • Andersen, M.E., Krewski, D. and Withey, J.R. (1993) Physiological pharmacokinetics and cancer risk assessment. Cancer Lett., 69, 1–14.

    Article  Google Scholar 

  • Andersen, M.E. and Krishnan, K. (1994) Physiologically based pharmacokinetics and cancer risk assessment. Environ. Health Perspect., 102, Suppl. 1, 103–108.

    Article  Google Scholar 

  • Aso, T. and Abiko, Y. (1978) Tissue distribution of arsenic after subcutaneous implantation of arsenic trioxide pellet in rats. J. Toxicol. Sci., 3, 109–15.

    Article  Google Scholar 

  • Astrup, P. (1968) [Blackfoot disease. Endemic incidence of peripheral arteriosclerosis] Blackfoot disease. Endemisk forekomst af perifer arteriosklerose. Ugeskr. Laeger, 130, 1807–15.

    Google Scholar 

  • Baker, E.L., Hayes, C.G., Landrigan, P.J. et al. (1977) A nationwide survey of heavy metal absorption in children living near primary copper, lead, and zinc smelters. Am. J. Epidemiol., 106, 261–73.

    Google Scholar 

  • Bates, M.N., Smith, A.H. and Hopenhayn-Rich, C. (1992) Arsenic ingestion and internal cancers: a review. Am. J. Epidemiol., 135, 462–76.

    Google Scholar 

  • Berg, S. (1977) [Identification value of the human hair] Der Identifizierungswert des menschlichen Haares. Arch. Kriminol., 159, 65–73.

    Google Scholar 

  • Buchet, J.P., Roels, H., Lauwerys, R., et al. (1980) Repeated surveillance of exposure to cadmium, manganese, and arsenic in school-age children living in rural, urban, and nonferrous smelter areas in Belgium. Environ. Res., 22, 95–108.

    Article  Google Scholar 

  • Buchet, J.P., Lauwerys, R. and Roels, H. (1981a) Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int. Arch. Occup. Environ. Health, 48, 71–79.

    Article  Google Scholar 

  • Buchet, J.P., Lauwerys, R. and Roels, H. (1981b) Urinary excretion of inorganic arsenic and its metabolites after repeated ingestion of sodium metaarsenite by volunteers. Int. Arch. Occup. Environ. Health, 48, 111–18.

    Article  Google Scholar 

  • Buchet, J.P., Lauwerys, R., Vandevoorde, A. and Pycke, J.M. (1983) Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study. Food Chem. Toxicol., 21, 19–24.

    Article  Google Scholar 

  • Buchet, J.P., Geubel, A., Pauwels, S. et al. (1984) The influence of liver disease on the methylation of arsenite in humans. Arch. Toxicol., 55, 151–54.

    Article  Google Scholar 

  • Buchet, J.P., Pauwels, J. and Lauwerys, R. (1994) Assessment of exposure to inorganic arsenic following ingestion of marine organisms by volunteers. Environ. Res., 66, 44–51.

    Article  Google Scholar 

  • Ch’i, I.C. and Blackwell, R.Q. (1968) A controlled retrospective study of blackfoot disease, an endemic peripheral gangrene disease in Taiwan. Am. J. Epidemiol., 88, 7–24.

    Google Scholar 

  • Charbonneau, S.M., Spencer, K., Bryce, F. and Sandi, E. (1978) Arsenic excretion by monkeys dosed with arsenic-containing fish or with inorganic arsenic. Bull. Environ. Contam. Toxicol., 20, 470–77.

    Article  Google Scholar 

  • Chen, C.J., Chen, C.W., Wu, M.M. and Kuo, T.L. (1992) Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br. J. Cancer, 66, 888–92.

    Article  Google Scholar 

  • Chen, G.S., Asai, T., Suzuki, Y. et al. (1990) A possible pathogenesis for blackfoot disease — effects of trivalent arsenic (As2O3) on cultured human umbilical vein endothelial cells. J. Dermatol., 17, 599–608.

    Google Scholar 

  • Conolly, R.B. and Andersen, M.E. (1991) Biologically based pharmacodynamic models: tools for toxicological research and risk assessment. Ann. Rev. Pharmacol. Toxicol., 31, 503–23.

    Article  Google Scholar 

  • Crecelius, E.A. (1977) Changes in the chemical speciation of arsenic following ingestion by man. Environ. Health Perspect., 19, 147–50.

    Article  Google Scholar 

  • Deak, S.T., Csaky, K.G. and Waddell, W.J. (1976) Localization and histochemical correlation of 73As by whole-body autoradiography in mice. J. Toxicol. Environ. Health., 1, 981–84.

    Article  Google Scholar 

  • Deaton, M.A., Bowman, P.D., Jones, G.P. and Powanda, M.C. (1990) Stress protein synthesis in human keratinocytes treated with sodium arsenite, phenyldichloroarsine, and nitrogen mustard. Fundam. Appl. Toxicol., 14, 471–76.

    Article  Google Scholar 

  • Dutkiewicz, T. (1977) Experimental studies on arsenic absorption routes in rats. Environ. Health Perspect., 19, 173–76.

    Article  Google Scholar 

  • Edwards, W.C. and Clay, B.R. (1979) An investigation of an arsenic poisoning case. Vet. Hum. Toxicol., 21, 161–62.

    Google Scholar 

  • Fowler, B.A. (1977) International conference on environmental arsenic: an overview. Environ. Health Perspect., 19, 239–42.

    Article  Google Scholar 

  • Freeman, H.C., Uthe, J.F., Fleming, R.B. et al. (1979). Clearance of arsenic ingested by man from arsenic contaminated fish. Bull. Environ. Contam. Toxicol, 22, 224–29.

    Article  Google Scholar 

  • Georis, B., Cardenas, A., Buchet, J.P. and Lauwerys, R. (1990) Inorganic arsenic methylation by rat tissue slices. Toxicology, 63, 73–84.

    Article  Google Scholar 

  • Geubel, A.P., Mairlot, M.C, Buchet, J.P. et al. (1988) Abnormal methylation capacity in human liver cirrhosis. Int. J. Clin. Pharmacol. Res., 8, 117–22.

    Google Scholar 

  • Gottlieb, K., Koehler, J.R. and Tessari, J. (1993) Non-analytic problems in detecting arsenic and cadmium in children living near a cadmium refinery in Denver, Colorado. J. Expo. Anal. Environ. Epidemiol., 3, 139–53.

    Google Scholar 

  • Johnson, L.R. and Farmer, J.G. (1991) Use of human metabolic studies and urinary arsenic speciation in assessing arsenic exposure. Bull. Environ. Contam. Toxicoi, 46, 53–61.

    Article  Google Scholar 

  • Kent, J.C. and Johnson, D.W. (1979) Mercury, arsenic, and cadmium in fish, water, and sediment of American Falls Reservoir, Idaho, 1974. Pestic. Monit. J., 13, 35–40.

    Google Scholar 

  • Kollmer, W.E. (1990) The does response of arsenic in induced hair of the rat and its relation to the content in various organs following acute exposure. J. Trace Elem. Electrolytes. Health Dis., 4, 79–85.

    Google Scholar 

  • Kollmer, W.E. (1992) Arsenic in induced hair of the rat and its relation to the content in various organs during chronic exposure. J. Trace Elem. Electrolytes. Health Dis., 6, 11–14.

    Google Scholar 

  • Koons, R.D. and Peters, C.A. (1994) Axial distribution of arsenic in individual human hairs by solid sampling graphite furnace AAS. J. Anal. Toxicol., 18, 36–40.

    Google Scholar 

  • Lagerkvist, B.J. and Zetterlund, B. (1994) Assessment of exposure to arsenic among smelter workers: a five-year follow-up. Am. J. Ind. Med., 25, 477–88.

    Article  Google Scholar 

  • Lakso, J.U. and Peoples, S.A. (1975) Methylation of inorganic arsenic by mammals. J. Agric. Food Chem., 23, 674–76.

    Article  Google Scholar 

  • Lauwerys, R., Hubermont, G., Buchet, J.P. and Roels, H. (1977) Domestic water and lead exposure during pregnancy [letter]. Lancet 2, 1188.

    Article  Google Scholar 

  • Lauwerys, R.R., Buchet, J.P. and Roels, H. (1979) The determination of trace levels of arsenic in human biological materials. Arch. Toxicol., 41, 239–47.

    Article  Google Scholar 

  • Le, X.C., Cullen, W.R. and Reimer, K.J. (1994) Human urinary arsenic excretion after one-time ingestion of seaweed, crab, and shrimp. Clin. Chem., 40, 617–24.

    Google Scholar 

  • Lindgren, A., Vahter, M. and Dencker, L. (1982) Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or-arsenate. Acta Pharmacol. Toxicol. (Copenh), 51, 253–65.

    Article  Google Scholar 

  • Maes, D. and Pate, B.D. (1977) The absorption of arsenic into single human head hairs. J. Forensic Sci., 22, 89–94.

    Google Scholar 

  • Mahieu, P., Buchet, J.P., Roels, H.A. and Lauwerys, R. (1981) The metabolism of arsenic in humans acutely intoxicated by As2O3. Its significance for the duration of BAL therapy. Clin. Toxicoi., 18, 1067–75.

    Article  Google Scholar 

  • Marafante, E. and Vahter, M. (1984) The effect of methyltransferase inhibition on the metabolism of [74As]arsenite in mice and rabbits. Chem. Biol. Interact., 50, 49–57.

    Article  Google Scholar 

  • McKone, T.E. and Daniels, J.I. (1991) Estimating human exposure through multiple pathways from air, water, and soil. Regul Toxicol. Pharmacol., 13, 36–61.

    Article  Google Scholar 

  • Menzel, D.B., Ross, M., Oddo, S.V. et al. (1994) A physiologically based pharmacokinetic model for ingested arsenic. Environ. Geochem. Health, 16, 209–18.

    Google Scholar 

  • Mohri, T., Hisanaga, A. and Ishinishi, N. (1990) Arsenic intake and excretion by Japanese adults: a 7-day duplicate diet study. Food Chem. Toxicol., 28, 521–29.

    Article  Google Scholar 

  • Murer, A.J., Abildtrup, A., Poulsen, O.M. and Christensen, J.M. (1992) Effect of seafood consumption on the urinary level of total hydride-generating arsenic compounds. Instability of arsenobetaine and arsenocholine. Analyst, 117, 677–80.

    Article  Google Scholar 

  • Offergelt, J.A., Roels, H., Buchet, J.P. et al. (1992) Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites. Br. J. Ind. Med., 49, 387–93.

    Google Scholar 

  • Polissar, L., Lowry-Coble, K., Kaiman, D.A. et al. (1990) Pathways of human exposure to arsenic in a community surrounding a copper smelter. Environ. Res., 53, 29–47.

    Article  Google Scholar 

  • Pounds, C.A., Pearson, E.F. and Turner, T.D. (1979) Arsenic in fingernails. J. Forensic Sci. Soc., 19, 165–73.

    Article  Google Scholar 

  • Quatrehomme, G., Ricq, O., Lapalus, P. et al. (1992) Acute arsenic intoxication: forensic and toxicologic aspects (an observation). J. Forensic Sci., 37, 1163–71.

    Google Scholar 

  • Rasmussen, R.E. and Menzel, D.B. (1996) Variation in Human Sensitivity to the Genotoxic Effects of Arsenic. Mutation Res. (in press).

    Google Scholar 

  • Ridley, W.P., Dizikes, L.J. and Wood, J.M. (1977) Biomethylation of toxic elements in the environment. Science, 197, 329–32.

    Article  Google Scholar 

  • Roels, H., Buchet, J.P., Truc, J. et al. (1982) The possible role of direct ingestion on the overall absorption of cadmium or arsenic in workers exposed to CdO or As2O3 dust. Am. J. Ind. Med., 3, 53–65.

    Article  Google Scholar 

  • Saxena, J. and Howard, P.H. (1977) Environmental transformation of alkylated and inorganic forms of certain metals. Adv. Appl. Microbiol., 21, 185–226.

    Article  Google Scholar 

  • Smith, A.H., Hopenhayn-Rich, C, Bates, M.N. et al. (1992) Cancer risks from arsenic in drinking water. Environ. Health Perspect., 97, 259–67.

    Article  Google Scholar 

  • Tarn, G.K., Charbonneau, S.M., Lacroix, G. and Bryce, F. (1979) In vitro methylation of 74As in urine, plasma and red blood cells of human and dog. Bull. Environ. Contain. Toxicol., 22, 69–71.

    Article  Google Scholar 

  • Thapar, N.T., Guenthner, E., Carlson, C.W. and Olson, O.E. (1969) Dietary selenium and arsenic additions to diets for chickens over a life cycle. Poult. Sci., 48, 1987–93.

    Article  Google Scholar 

  • Tinwell, H., Stephens, S.C. and Ashby, J. (1991) Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler’s solution. Environ. Health Perspect., 95, 205–210.

    Google Scholar 

  • Tseng, W.P., Chu, H.M., How, S.W. et al. (1968) Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J. Natl. Cancer Inst., 40, 453–63.

    Google Scholar 

  • Vahter, M. (1981) Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environ. Res., 25, 286–93.

    Article  Google Scholar 

  • Vahter, M, Marafante, E. and Dencker, L. (1984) Tissue distribution and retention of 74As-dimethylarsinic acid in mice and rats. Arch. Environ. Contam. Toxicol., 13, 259–64.

    Article  Google Scholar 

  • Vahter, M. and Envall, J. (1983) In vivo reduction of arsenate in mice and rabbits. Environ. Res., 32, 14–24.

    Article  Google Scholar 

  • Vahter, M. and Marafante, E. (1983) Intracellular interaction and metabolic fate of arsenite and arsenate in mice and rabbits. Chem. Biol. Interact., 47, 29–44.

    Article  Google Scholar 

  • Walsh, L.M., Sumner, M.E. and Keeney, D.R. (1977) Occurrence and distribution of arsenic in soils and plants. Environ. Health Perspect., 19, 67–71.

    Article  Google Scholar 

  • Watanabe, T., Hirayama, T., Takahashi, T. et al. (1979) Toxicological evaluation of arsenic in edible seaweed, Hizikia species. Toxicology, 14, 1–22.

    Article  Google Scholar 

  • Wolfsperger, M., Hauser, G., Gossler, W. and Schiagenhaufen, C. (1994) Heavy metals in human hair samples from Austria and Italy: influence of sex and smoking habits. Sci. Total. Environ., 156, 235–42.

    Article  Google Scholar 

  • Wood, J.M., Cheh, A., Dizikes, L.J. et al. (1978) Mechanisms for the biomethylation of metals and metalloids. Fed. Proc, 37, 16–21.

    Google Scholar 

  • Yamauchi, H. and Yamamura, Y. (1979) [Urinary inorganic arsenic and methylarsenic excretion following arsenate-rich seaweed ingestion (author’s transl.)]. Sangyo. Igaku., 21, 47–54.

    Article  Google Scholar 

  • Yeh, S. (1973) Skin cancer in chronic arsenicism. Hum. Pathol., 4, 469–85.

    Article  Google Scholar 

  • Yu, H.S. (1984) Blackfoot disease and chronic arsenism in southern Taiwan. Int. J. Dermatol., 23, 258–60.

    Article  Google Scholar 

  • Yu, H.S., Sheu, H.M., Ko, S.S. et al. (1984) Studies on blackfoot disease and chronic arsenism in southern Taiwan: with special reference to skin lesions and fluorescent substances. J. Dermatol., 11, 361–70.

    Google Scholar 

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  1. D. B. Menzel
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Editors and Affiliations

  1. US Environmental Protection Agency, Washington, DC, USA

    Charles O. Abernathy  & Rebecca L. Calderon  & 

  2. University of Colorado, USA

    Willard R. Chappell (Professor of Physics) (Professor of Physics)

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Menzel, D.B. (1997). Some Results of a Physiologically Based Pharmacokinetic Modeling Approach to Estimating Arsenic Body Burdens. In: Abernathy, C.O., Calderon, R.L., Chappell, W.R. (eds) Arsenic. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5864-0_28

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  • DOI: https://doi.org/10.1007/978-94-011-5864-0_28

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