Review : Toxicology of Volatile Organic Compounds in Indoor Air and Strategy for Further Research

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Abstract
Indoor air is a variable complex mixture of chemicals and airborne particles. Volatile organic compounds (VOC) constitute a major group of indoor air pollutants encompassing diverse chemicals such as aldehydes, terpenes, and aromatic, aliphatic and halogenated hydrocar bons. Of many of these compounds, our knowledge of their possible health effects is very limited. To improve the situation, combined information should be assembled about the nature of VOC, the degree of human exposure, the number of people exposed and, most importantly, the toxicology of VOC. Evidence of carcinogenic potential in animals is con vincing for formaldehyde and acetaldehyde vapor. Formaldehyde carcinogenesis is a high- dose phenomenon with a determining role for cytolethality. This may also be true for acetal dehyde carcinogenesis, but further studies are needed to verify this assumption. Being a reac tive, potent DNA-protein cross-linker and a major indoor air contaminant, acrolein should be tested in a long-term rat inhalation carcinogenicity study. Studies with combinations of aldehydes, including superimposed peak exposures, would contribute a great deal to a realis tic health hazard assessment of this class of compounds. Short-term inhalation toxicity stud ies, including toxicokinetics of a number of relevant terpenes, are deemed desirable to find out whether this category of chemicals forms a priority indoor air issue. Benzene is a human carcinogen at high hemotoxic exposure levels. There is evidence to suggest that at non-hemo toxic exposure concentrations the risk of leukemia decreases more than proportionally, soon becoming negligibly small. In comparison with benzene, detoxification of toluene and xylene is rapid which may explain the non-carcinogenicity of these benzene homologues. In non- occupational situations, indoor air hexane concentrations are orders of magnitude lower than exposure levels associated with clinically overt neuropathy. Therefore, hexane is not regarded as an indoor air pollutant of major concern. Main elements of a strategy for further toxicolog ical studies of (VOC in) indoor air include: (a) setting of priorities for testing individual compounds, classes of compounds and combinations of compounds; (b) identification of the type of information to be assembled; (c) prediction and experimental verification of syner gism or additiveness between compounds; (d) application of biologically or physiologically based pharmacokinetic modelling to optimize extrapolation of toxicodynamic data obtained in fixed-time animal experiments to low-dose/long-time human situations, and (e) (geno)tox icity testing of relevant existing combinations of chemicals (e.g. 20 to 30) at concentrations of, e.g., a factor 3 or 10 higher than those occurring in indoor air. Studies along the last- mentioned practical line may be very helpful in narrowing down the number of indoor situa tions of real health concern.