Ethanol [MAK Value Documentation, 2018]

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) and the Pregnancy Risk Group of ethanol [ 64‐17‐5 ]. Ethanol is produced endogenously. Uptake of greater amounts depresses the central nervous system and is carcinogenic especially for the liver. The former MAK value of 500 ml/m 3 was derived from a study in exposed subjects at rest. It was calculated that at 500 ml/m 3 the AUC (product of the blood ethanol concentration and time of exposure) was similar to the standard deviation of the lifetime AUC of endogenous ethanol. At 50 W physical activity, which corresponds to a respiratory volume of 10 m 3 per day, the blood concentration of ethanol is about twice as high as compared with that of subjects in rest. Therefore, taking into account the increased respiratory volume at the workplace (see List of MAK‐ and BAT Values, Sections I b and I c), the MAK value is now lowered to 200 ml/m 3 . Since a systemic effect is critical, Peak Limitation Category II is retained. As irritation was observed at 1900 ml/m 3 , the excursion factor is now set to 4. After oral uptake, ethanol causes developmental toxicity. The lowest reported concentration of ethanol in the blood in pregnant rats causing effects in the F1‐generation was 300 mg/l with a NOAEC of 70 mg/l. In an inhalation study, the NOAEC for developmental neurotoxicity in rats was 10 000 ml/m 3 which according to a PBPK model corresponds to a concentration of ethanol in the blood of about 65 mg/l. These NOAEC are more than 10 times as high as the ethanol concentration of 1 mg/l in humans exposed to 200 ml/m 3 even considering the increased respiratory volume at the workplace. Therefore, ethanol remains assigned to Pregnancy Risk Group C.

The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment

“…JEFCA concluded that the use of ethanol as an extraction solvent should be restricted to usage determined by good manufacturing practice, in which case residues are unlikely to have any toxicological effects and that ethanol posed no safety concern at the levels of intake resulting from use of ethyl esters as flavouring agents (JEFCA 1970). The German Research Foundation (DFG) MAK commission has rated ethanol and acetaldehyde as class 5 carcinogens (Hartwig and MAK commission 2018). This class comprises compounds that cause or are considered to cause cancer in humans or animals for which a MAK value can be derived.…”

“…The same committee further calculated an additional breast cancer risk of 4/10 3 after 40 years exposure towards 1300 mg/m 3 . In addition, the German MAK commission considered thatbased on the variation of the endogenous exposure-an occupational exposure of 200 mL/m 3 (380 mg/m 3 ) would be within the standard deviation of the lifetime AUC and thus would contribute only little to the cancer risk (Hartwig and MAK commission 2018).…”