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Diazinon [MAK Value Documentation, 2015]


Hartwig, A; MAK Commission; et al; Arand, Michael (2017). Diazinon [MAK Value Documentation, 2015]. The MAK Collection for Occupational Health and Safety, 2(4):1473-1544.

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated diazinon [333‐41‐5] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect of diazinon is inhibition of the acetylcholinesterase (AChE) at the cholinergic synapses which is measured as AChE activity in erythrocytes and brain. A reduction to 70 and 80% of their respective activities prior to exposure is regarded as adverse. The corresponding NOAELs in subchronic or chronic feeding studies in rats, dogs and monkeys are 0.3, 0.75 and 0.17 mg/kg body weight and day, which are scaled to concentrations of 0.6, 4.5 and 0.7 mg/m3, respectively. Taking into account a possible enhancement of the effects over time, the maximum concentration at the workplace (MAK value) of 0.1 mg/m3 for the inhalable fraction is confirmed. The MAK value is also supported by a 3‐week inhalation study in rats with a NOAEC of 0.46 mg/m3.
Since a systemic effect is critical, Peak Limitation Category II is retained. The renal elimination half‐life of the dialkyl phosphate metabolites of diazinon in humans is about 2 hours, so that the corresponding excursion factor of 2 is confirmed.
The NOAELs for developmental toxicity are 1.9 mg/kg body weight and day for rats and 100 mg/kg body weight and day for rabbits. As developmental neurotoxicity is induced only at higher doses, the offspring are less sensitive to the inhibition of AChE than the dams, and the margins between the calculated concentrations without effects and the MAK value are sufficiently large, the classification of diazinon in Pregnancy Risk Group C is retained.
Diazinon is not considered to be genotoxic, and therefore not regarded as a germ cell mutagen. In studies not reaching the maximum tolerated dose, diazinon is not carcinogenic in rats and mice. Skin contact is expected to contribute significantly to systemic toxicity, and diazinon remains designated with an “H”. Limited data in animals do not show a skin sensitizing potential.

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated diazinon [333‐41‐5] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect of diazinon is inhibition of the acetylcholinesterase (AChE) at the cholinergic synapses which is measured as AChE activity in erythrocytes and brain. A reduction to 70 and 80% of their respective activities prior to exposure is regarded as adverse. The corresponding NOAELs in subchronic or chronic feeding studies in rats, dogs and monkeys are 0.3, 0.75 and 0.17 mg/kg body weight and day, which are scaled to concentrations of 0.6, 4.5 and 0.7 mg/m3, respectively. Taking into account a possible enhancement of the effects over time, the maximum concentration at the workplace (MAK value) of 0.1 mg/m3 for the inhalable fraction is confirmed. The MAK value is also supported by a 3‐week inhalation study in rats with a NOAEC of 0.46 mg/m3.
Since a systemic effect is critical, Peak Limitation Category II is retained. The renal elimination half‐life of the dialkyl phosphate metabolites of diazinon in humans is about 2 hours, so that the corresponding excursion factor of 2 is confirmed.
The NOAELs for developmental toxicity are 1.9 mg/kg body weight and day for rats and 100 mg/kg body weight and day for rabbits. As developmental neurotoxicity is induced only at higher doses, the offspring are less sensitive to the inhibition of AChE than the dams, and the margins between the calculated concentrations without effects and the MAK value are sufficiently large, the classification of diazinon in Pregnancy Risk Group C is retained.
Diazinon is not considered to be genotoxic, and therefore not regarded as a germ cell mutagen. In studies not reaching the maximum tolerated dose, diazinon is not carcinogenic in rats and mice. Skin contact is expected to contribute significantly to systemic toxicity, and diazinon remains designated with an “H”. Limited data in animals do not show a skin sensitizing potential.

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Item Type:Journal Article, not_refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:27 October 2017
Deposited On:17 Oct 2019 10:41
Last Modified:23 Oct 2019 14:38
Publisher:Wiley-VCH Verlag
ISSN:2509-2383
ISBN:9783527600410
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/3527600418.mb33341e5917

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