Sulfur mustard as a carcinogen: Application of relative potency analysis to the chemical warfare agents H, HD, and HT

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Abstract

A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 × 10−4 mg HD/m3 and the occupational exposure level of 3 × 10−3 mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 × 10−8 and 1 × 10−7. Lifetime cancer risk estimates ⩽ 10−6 are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10−5 for the general public and 10−4 for the worker population. These values are considered upper limit estimates.

References (68)

  • T.D. Jones et al.

    A unifying concept for carcinogenic risk assessments

    J. Theor. Biol.

    (1983)
  • R. Vogt et al.

    Pathogenesis of skin lesions caused by sulfur mustard

    Fundam. Appl. Toxicol.

    (1984)
  • S. Wada et al.

    Mustard gas as a cause of respiratory neoplasia in man

    Lancet

    (1968)
  • B.N. Ames et al.

    Ranking possible carcinogenic hazards

    Science

    (1987)
  • E.L. Anderson et al.

    Quantitative approaches in use to assess cancer risk

    Risk Anal.

    (1983)
  • H.B. Andervont

    Biologic testing of carcinogens. II. Pulmonary-tumor induction technique

    J. Natl. Cancer Inst.

    (1940)
  • G. Beebe

    Lung cancer in World War I veterans: Possible relation to mustard-gas injury and 1918 influenza epidemic

    J. Natl. Cancer Inst.

    (1960)
  • I. Berenblum

    The modifying influence of dichloroethyl sulfide on the induction of tumors in mice by tar

    J. Pathol. Bacteriol.

    (1929)
  • W.R. Bryan et al.

    Quantitative analysis of dose-response data obtained with three carcinogenic hydrocarbons in strain C3H male mice

    J. Natl. Cancer Inst.

    (1943)
  • M.K. Buening et al.

    Fluorine substitution as a probe for the role of the 6-position of benzo(a)pyrene in carcinogenesis

    J. Natl. Cancer Inst.

    (1983)
  • R. Case et al.

    Mustard gas poisoning, chronic bronchitis and lung cancer. An investigation into the possibility that poisoning by mustard gas in the 1914–1918 war might be a factor in the production of neoplasia

    Brit. J. Prev. Soc. Med.

    (1955)
  • H. Fell et al.

    The effect of repeated applications of minute quantities of mustard gas on the skin of mice

    Cancer Res.

    (1948)
  • L.R. Glass

    Use of Short-Term Test Systems for the Prediction of the Hazard Represented by Potential Chemical Carcinogens

  • R.E. Gosselin et al.
  • L. Halberstaedter

    A benzpyrene tumour strain in hamsters with tendency to metastasis formation

    Nature (London)

    (1939)
  • W.E. Heston

    Inheritance of susceptibility to spontaneous pulmonary tumors in mice

    J. Natl. Cancer Inst.

    (1942)
  • W.E. Heston

    Carcinogenic action of the mustards

    J. Natl. Cancer Inst.

    (1950)
  • W.E. Heston

    Occurrence of tumors in mice injected subcutaneously with sulfur mustard and nitrogen mustard

    J. Natl. Cancer Inst.

    (1953)
  • W.E. Heston et al.

    Pulmonary tumors in Strain A mice exposed to mustard gas

  • F. Homburger et al.

    Inherited susceptibility of inbred strains of Syrian hamsters to induction of subcutaneous sarcomas and mammary and gastrointestinal carcinomas by subcutaneous and gastric administration of polynuclear hydrocarbons

    Cancer Res.

    (1972)
  • W.C. Hueper et al.

    Carcinogenic bioassay on air pollutants

    Arch. Pathol.

    (1962)
  • C.H. Hunter et al.
  • ICF Inc

    Discussion of Options for Revising the Hazard Ranking System (HRS) Toxicity Factor

  • S. Inada et al.

    Multiple Bowen's Disease observed in former workers of poison gas factory in Japan, with special reference to mustard gas exposure

    J. Dermatol.

    (1978)
  • International Agency for Research on Cancer (IARC)
  • T.D. Jones

    A unifying concept for carcinogenic risk assessments: Comparison with radiation-induced leukemia in mice and men

    Health Phys.

    (1984)
  • T.D. Jones et al.

    Permissible concentrations of chemicals in air and water derived RTECS entries: A “RASH” chemical scoring system

    J. Toxicol. Ind. Health

    (1985)
  • T.D. Jones et al.

    Animal studies and prediction of human tumors can be aided by graphical sorting of animal data

    Amer. J. Ind. Med.

    (1985)
  • T.D. Jones et al.

    Evaluation of Human Health Risks from Mixtures of Hazardous Chemicals and Radionuclides

  • T.D. Jones et al.

    Chemical scoring by a Rapid Screening Hazard (RASH) method

    Risk Anal.

    (1988)
  • N. Klehr

    Cutaneous late manifestations in former mustard gas workers

    Z. Hautkrankh.

    (1984)
  • R.L. Lewis et al.
  • K. Lohs
  • B.P. McNamara et al.

    Toxicological Basis for Controlling Levels of Mustard in the Environment

    Edgewood Arsenal Special Publication EB-SP-74030

    (1975)
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