Diethylbenzene (all isomers) [MAK value documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: July 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated diethylbenzene as mixture of isomers [
25340‐17‐4
], as well as the individual isomers 1,2‐diethylbenzene [
135‐01‐3
], 1,3‐diethylbenzene [
141‐93‐5
] and 1,4‐diethylbenzene [
105‐05‐5
] considering all toxicological end points. Available publications and unpublished studies are described in detail. 1,2‐Diethylbenzene is the most toxic of the isomers, the critical effect being peripheral neurotoxicity which is due to a gamma‐diketone formed metabolically. In subchronic inhalation and oral studies in rats with diethylbenzene mixtures containing 1,2‐diethylbenzene, subclinical neurotoxicity is observed at all concentrations and doses used. From these studies a maximum concentration at the workplace (MAK value) of 1 ml/m
3
is set for 1,2‐diethylbenzene. For a diethylbenzene mixture containing 10% 1,2‐diethylbenzene, the critical effect in rats is leuco‐ and lymphopenia. A MAK value of 5 ml/m
3
is set for diethylbenzene mixtures and the MAK value for 1,2‐diethylbenzene has to be observed additionally. In rats, critical end points for 1,3‐diethylbenzene are increased liver and thyroid weight and for 1,4‐diethylbenzene altered clinical chemical parameters and increased kidney weight. A MAK value of 5 ml/m
3
for both isomers is derived.

Since systemic effects are critical, Peak Limitation Category II is designated for all isomers. As peripheral neurotoxicity is a cumulative effect, an excursion factor of 8 is set for 1,2‐diethylbenzene. The default excursion factor of 2 for systemically acting substances is set for diethylbenzene mixtures as well as 1,3‐ diethylbenzene and 1,4‐diethylbenzene as their half‐lives are not known. Thus, the allowable peak exposures are lower than those of other alkyl benzenes and also prevent from irritation.

By analogy with acrylamide it is deduced that rats exposed in utero to 1,2‐diethylbenzene are not more susceptible to peripheral neurotoxicity than adult animals. The oral NOAEL for developmental toxicity of 1,2‐diethylbenzene in rats is scaled to a concentration of 17 ml/m
3
at the workplace. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and 1,2‐diethylbenzene is assigned to Pregnancy Risk Group C. The oral NOAEL for developmental toxicity of a diethylbenzene mixture in rats is scaled to a concentration of 94 ml/m
3
at the workplace. Developmental toxicity studies with 1,3‐diethylbenzene and 1,4‐diethylbenzene are lacking, however, these isomers are contained in the diethylbenzene mixture to about 60% and 30%, respectively. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and diethylbenzene mixtures as well as 1,3‐diethylbenzene and 1,4‐diethylbenzene are assigned to Pregnancy Risk Group C.

Diethylbenzenes are not genotoxic in vitro and in vivo. In a carcinogenicity study dermal application of a diethylbenzene mixture induced a single squamous carcinoma in mice, which is judged not sufficient for classification as a carcinogen. According to skin absorption models, percutaneous absorption can contribute significantly to systemic toxicity and all diethylbenzene isomers are designated with an “H” notation. Limited data show no sensitization.