Technical report 122

German MAK-Commission

Contrary to the chemical carcinogen classification schemes of the UN GHS, EU CLP or IARC, the German Committee for the determination of occupational exposure limits (‘MAK-Commission’) considers the mode of action of tumour development in its classification scheme. It distinguishes the following 5 groups:

Group 1: Substances that cause cancer in humans;
Group 2: Substances that are considered to be carcinogenic in humans;
Group 3: Substances that cause concern of being carcinogenic to humans but which cannot be conclusively evaluated due to lack of data;
Group 4: Substances with carcinogenic potential for which a non-genotoxic mode of action is of prime importance; no significant contribution to human cancer risk is expected at exposures at MAK and BAT values;
Group 5: Substances with carcinogenic and genotoxic effects; the potency of these substances is considered to be so low that, provided MAK and BAT limit values are respected, no significant contribution to human cancer risk is to be expected.

With categories 4 and 5 the MAK commission identifies those substances which have been shown to cause carcinogenicity for which a safety threshold can be established.

In 2011, the German MAK-Commission reviewed the epidemiological and animal data available for the inhalation toxicity of granular persistent dusts (GBS), the German analogue to PSP, and kept its existing occupational exposure limit for GBS at 4 mg/m3 for the inhalable fraction and lowered the existing limit of 1.5 mg/m3 to 0.3 mg/m3 for the respirable fraction.

In addition to lowering the existing MAK value for the respirable fraction of GBSs, the MAK-Commission classified GBS as a Category 4 carcinogen. Under the MAK carcinogenicity classification scheme, Category 4 carcinogens are substances with carcinogenic potential for which a non-genotoxic mode of action is of prime importance and no significant contribution human cancer risk is expected at exposures below the MAK (or BAT) value. Such classification is generally applied to substances for which the mode of action is well understood and the tumorigenic responses are related for example to increases in cellular proliferation, inhibition of apoptosis or disturbances in cellular differentiation.

The MAK-Commission justified the classification of GBS as Category 4 carcinogens on the basis of existing evidence that inhalation exposure to high levels of GBS leads to inflammation in the bronchial and alveolar region and associated release of radical oxygen species leading to tumour formation in the rat. It was concluded that the effects seen in the rat are also applicable to humans.