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Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

The “closed chamber technique” (CCT) is presented. It allows investigation of pharmacokinetics of volatile substances in vivo in animals and in man and in vitro using tissue fractions. During the exposure period only the atmospheric concentrations of the substance are measured. The concentration-time data obtained are pharmacokinetically analyzed by a two compartment model describing uptake, endogenous production and excretion of the unchanged substance and its metabolic elimination. Using this model, pharmacokinetics of ethylene have been determined in rats and man. For both species, the results compared well with an estimation based on an allometric species scaling. Furthermore, the applicability of CCT is demonstrated in vivo on several other gases and vapors of solvents, e.g. trichloroethylene and 1,1,1-trichloroethane, and in vitro on 1,2-epoxybutene-3.

The pharmacokinetics of ethylene and 1,3-butadiene were studied in male Sprague-Dawley rats by use of a closed inhalation chamber system. Both compounds showed saturable metabolism when untreated rats were used. "Linear" pharmacokinetics applied at exposure concentrations below 800 ppm ethylene and below 1,000 ppm 1,3-butadiene. A constant elimination rate, indicative of metabolic saturation, occurred at concentrations higher than 1,000 ppm ethylene or 1,500 ppm 1,3-butadiene. Pretreatment with aroclor 1254 (polychlorinated biphenyls) increased Vmax for both compounds. For 1,3-butadiene, no saturation of metabolic capacity was observed with exposure concentrations up to 12,000 ppm when the rats were pretreated with aroclor 1254. A comparison with previous studies on ethane and n-pentane suggested that introduction of a double bond into a saturated aliphatic hydrocarbon increased the rate of metabolism under conditions in vivo.