Last year an ECETOC task force finalised guidance on how to classify carcinogens under the criteria for a globally harmonised system of classification and labelling of chemicals (GHS) developed by the United Nations Conference on Environment and Development (UNCED). The paper has just been published in Critical Reviews in Toxicology (see latest publications).
With regard to carcinogenicity, GHS distinguishes between Category 1 (“known or presumed human carcinogens’) and Category 2 (“suspected human carcinogens’). Category 1 carcinogens are divided into Category 1A (“known to have carcinogenic potential for humans’), based largely on human evidence, and 1B (“presumed to have carcinogenic potential for humans’), based largely on experimental animal data. Concerns have been raised that the criteria for applying these carcinogenicity classifications are not sufficiently well defined and potentially allow different conclusions to be drawn.
Classification under GHS, like other systems in place, is for hazard, there being no consideration of potency or risk assessment, including exposure considerations. Such elements are being taken into account in the ECETOC scheme. A wide range of carcinogenic potency can be observed both in human epidemiological studies and in animal experiments. The following cut-off values for high and low potency for different exposure scenarios are proposed:
Cut-off values for substances of high and low potency (based on guidance
values to assist in Category 1 and 2 classification for chronic toxicity; UN, 2007)
|High potency||<10mg/kg oral, <20mg/kg dermal, or inhalation <0.02mg/L vapour, <0.02mg/L dust/mist/fume|
|>low potency||>10mg/kg oral, >20mg/kg dermal, or inhalation >50ppm gas,
>0.02mg/L vapour, > 0.02mg/L dust/mist/fume
The ECETOC paper lays out a series of questions (shown in figure 2.) to be applied during the evaluation of data from experiments with rodents; epidemiological data which could lead to Category 1A are not considered in this scheme. Answers to each question can lead either to a classification decision or to the next question.
Stepwise approach to the classification of a substance, not otherwise classifiable as
It is being pointed out that this process should only be implemented in an environment of informed scientific opinion. Detailed guidance is provided on how to address these questions in determining carcinogen classification. It was concluded that mode of action and potency are probably the most important of the above-mentioned factors. The scheme is illustrated with five case studies: thiamethoxam, melamine, dichlorvos, formaldehyde, and Sudan I.
Reference to the ECETOC scheme has been made in the report of the REACH Implementation Project – RIP 3.6 (on the introduction of the GHS guidelines into the new EU chemicals legislation).
The task force presented first concepts for wider input at EUROTOX 2007, at the ECETOC-organised session “Carcinogen Classification – Moving from a hazard to a risk-based system’, and the final scheme at last year’s European meeting of the Toxicology Forum.