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1,4‐Dichlorobenzene [MAK Value Documentation, 2018]


Hartwig, A; MAK Commission; Arand, Michael; et al (2019). 1,4‐Dichlorobenzene [MAK Value Documentation, 2018]. The MAK Collection for Occupational Health and Safety, 4(4):1931-1982.

Abstract

The German Commission for the investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 1,4‐dichlorobenzene [106‐46‐7] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.

In mouse liver, 1,4‐dichlorobenzene causes carcinoma after oral and inhalation exposure and is mitogenic and cytotoxic. In reliable studies it is not genotoxic. As a non‐genotoxic mechanism is of prime importance and genotoxic effects play at most a minor part, provided the maximum concentration at the workplace (MAK value) is observed, 1,4‐dichlororbenzene is now classified in Category 4 for carcinogenic substances.

The chronic local NOAEC of 20 ml/m3 for changes in the olfactory epithelium of the rat nose would correspond to a MAK value of 10 ml/m3. However, the most sensitive toxicological effect is hepatocellular hypertrophy with a LOAEL of 10 mg/kg body weight and day in an oral 52‐week study with dogs. Because of the low severity and incidence of the effect, a NAEL (no adverse effect level) of 5 mg/kg body weight and day is assumed. This NAEL is scaled to a MAK value of 2 ml/m3.

Since a systemic effect is critical, Peak Limitation Category II is assigned. As it is not known if the effects are due to the metabolites or 1,4‐dichlorobenzene itself, the default excursion factor of 2 is assigned.

The NOAECs for developmental toxicity in rats and rabbits are 500 and 100 ml/m3, respectively, and the differences to the MAK value are sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and 1,4‐dichlorobenzene is assigned to Pregnancy Risk Group C. Skin contact may contribute significantly to systemic toxicity and 1,4‐dichlorobenzene remains designated with an “H” notation. Sensitization is not expected from the limited data.

Abstract

The German Commission for the investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 1,4‐dichlorobenzene [106‐46‐7] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.

In mouse liver, 1,4‐dichlorobenzene causes carcinoma after oral and inhalation exposure and is mitogenic and cytotoxic. In reliable studies it is not genotoxic. As a non‐genotoxic mechanism is of prime importance and genotoxic effects play at most a minor part, provided the maximum concentration at the workplace (MAK value) is observed, 1,4‐dichlororbenzene is now classified in Category 4 for carcinogenic substances.

The chronic local NOAEC of 20 ml/m3 for changes in the olfactory epithelium of the rat nose would correspond to a MAK value of 10 ml/m3. However, the most sensitive toxicological effect is hepatocellular hypertrophy with a LOAEL of 10 mg/kg body weight and day in an oral 52‐week study with dogs. Because of the low severity and incidence of the effect, a NAEL (no adverse effect level) of 5 mg/kg body weight and day is assumed. This NAEL is scaled to a MAK value of 2 ml/m3.

Since a systemic effect is critical, Peak Limitation Category II is assigned. As it is not known if the effects are due to the metabolites or 1,4‐dichlorobenzene itself, the default excursion factor of 2 is assigned.

The NOAECs for developmental toxicity in rats and rabbits are 500 and 100 ml/m3, respectively, and the differences to the MAK value are sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and 1,4‐dichlorobenzene is assigned to Pregnancy Risk Group C. Skin contact may contribute significantly to systemic toxicity and 1,4‐dichlorobenzene remains designated with an “H” notation. Sensitization is not expected from the limited data.

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Additional indexing

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:German
Date:13 November 2019
Deposited On:04 Feb 2020 14:57
Last Modified:29 Jul 2020 12:26
Publisher:Wiley-VCH Verlag
ISSN:2509-2383
ISBN:9783527600410
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/3527600418.mb10646e6519

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