Quantitating the Production of Biological Reactive Intermediates in Target Tissues: Example, Dichloromethane

  • Richard H. Reitz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Dichloromethane (CH2C12, DCM) is a widely used industrial solvent. In addition to industrial applications such as film processing, it has been used for the preparation of consumer products such as cosmetics, decaffeinated coffee, and paint strippers. With such a wide potential for human exposure to DCM, the need for a good toxicology database is obvious, and a number of acute, subchronic, and chronic studies have been conducted with this material. In general the results from these studies have been reassuring until the National Toxicology Program completed a long term inhalation bioassay of methylene chloride in rats and mice (NTP, 1985).


Syrian Golden Hamster Inhalation Study National Toxicology Program B6C3F1 Mouse Conjugative Pathway 
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  1. Ahmed, A.E., and Anders, M.W. (1976). Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies. Drug. Metab. Dispos., 4, 357–361.Google Scholar
  2. Andersen, M.E., Clewell, H.J., Gargas, M.L., Smith, F.A., and Reitz, R.H. (1987). Physiologically-based pharmacokinetics and the risk assessment process for methylene chloride. Toxicol. Appi. Pharmacol. 87, 185–205.CrossRefGoogle Scholar
  3. Burek, J.D., Nitschke, K.D., Bell, T.J., Wackerle, D.L., Childs, R.C., Beyer, J.D., Dittenber, D.A., Rampy, L.W., and McKenna, M.J. (1984). Methylene chloride: A 2 year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam. Appi. Toxicol., 4, 30–47.CrossRefGoogle Scholar
  4. Gargas, M.L., Clewell, H.J., and Andersen, M.E., (1986). Metabolism of inhaled dihalomethanes in vivo: differentiation of kinetic constants for two independent pathways. Toxicol. Appl. Pharmacol., 82, 211–223.Google Scholar
  5. Howe, R.B., and Crump, K.S., (1982). GLOBAL83: A computer program to extrapolate quantal animal toxicity data to low doses (May, 1982). OSHA Contract No. 41USC252C3.Google Scholar
  6. Kubic, V.L., Anders, M.W., Engel, R.R., Barlow, C.H., and Caughey, W.S. (1974). Metabolism of dihalomethanes to carbon monoxide. I. In vivo studies. Drug. Metab. Dispos., 2, 53–57.Google Scholar
  7. Miller, E.C., and Miller, J.A., (1966). Mechanisms of chemical carcinogenesis: Nature of proximate carcinogens and interactions with macromolecules. Pharmacol. Rev., 18, 805.Google Scholar
  8. National Toxicology Program (NTP) (1985). NTP Technical Report on the Toxicology and Carcinogenesis Studies of Dichloromethane in F-344/N Rats and B6C3F1 Mice (Inhalation Studies). NTP-TR-306 (board draft).Google Scholar
  9. Reitz, R.H., Mendrala, A.L., Park, C.N., Andersen, M.E., and Guengerich, F.P. (1988). Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: Implications for risk assessment. Toxicology Letters, 43, 97–116.CrossRefPubMedGoogle Scholar
  10. Reitz, R.H., Mendrala, A.L. and Guengerich, F.P. (1989). In Vitro Metabolism of Methylene Chloride in Human and Animal Tissues: Use in Physiologically-Based Pharmacokinetic Models. Toxicol. Appl. Pharmacol. 97, 230–246.Google Scholar
  11. Serota, D., Ulland, B., and Carlborg, F. (1984). Hazelton Chronic Oral Study in Mice. Food Solvents Workshop I: Methylene Chloride, March 8–9, Bethesda, Maryland.Google Scholar
  12. Singh, D.V., Spitzer, H.L., and White, P.D. (1985). Addendum to the Health Assessment Document for Dichloromethane (Methylene Chloride). Updated carcinogenicity assessment of dichloromethane. EPA/600/8–82/004F.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Richard H. Reitz
    • 1
  1. 1.Chemical Industry Institute of ToxicologyResearch Triangle ParkUSA

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