Page 361 - Industrial Ventilation Design Guidebook

S3 TOX1CITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 3 I 7

TABLE 5.21 Classification of Carcinogenicity of Chemicals According
to the International Agency on Research on Cancer

Class Explanation

1 , Carcinogenic to humans Enough epidemiological evidence on
carcinogenicity in humans
2A. Probably carcinogenic to humans Limited evidence on carcinogenicity in humans
and sufficient evidence on carcinogenicity in
experimental animals and other relevant
evidence
2B. Possibly carcinogenic to humans Limited evidence on carcinogenicity in humans,
and other relevant evidence missing;
occasionally a compound with insufficient
human evidence but limited evidence on
carcinogenicity in experimental animals
3. Not classifiable Not enough scientifically relevant data
available for classification
4. Probably not carcinogenic in Evidence both in humans and experimental
humans animals indicates a lack of carcinogenicity
Source: Modified from Vahakangas and Savolainen. 179

Since animals are biological systems which differ from humans in
many ways, epidemiological evidence on the carcinogenicity of chemicals
is naturally much stronger than that derived from experimental animal
studies. However, it is often difficult to obtain conclusive evidence due to
several problems which are characteristic of epidemiological studies (see
Section 5.3 IPR, pages 3-5). It should also be noted that agents causing
very rare types of cancer are much easier to detect than those causing
more common cancers. Angiosarcoma of the liver and adenocarcinoma
of the nose are rare cancers (annual incidences about one per million in
the general population); therefore, the human carcinogenicity of vinyl
chloride (angiosarcoma) and wood dust (adenocarcinoma of nasal cavity)
was identified on the basis of a few cases, whereas increased risk of lung
cancer (annual incidence about 400-500 per million) is much more diffi-
cult to demonstrate. However, when the evidence derived from experi-
mental animal studies on the carcinogenicity of a given chemical is
utilized in assessing human risks of chemical carcinogenesis, several new
'
"
difficulties are encountered. 178 180 182
The biotransformation of a given chemical compound in experimen-
tal animals and in humans may differ. Furthermore, high doses of chemi-
cal compounds are used in studies with experimental animals, and this
may cause alterations in biotransformation of the tested chemicals that
do not occur at the lower doses relevant to the human exposure situa-
tion. For example, a metabolic pathway dominating at low doses may be-
come saturated, and a salvage metabolic pathway, e.g., one that produces
reactive intermediates of the compound, may become involved in the
biotransformation of the chemical. Since this intermediate could never be
produced at the exposure levels encountered in humans, the overall result