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Hexachlorbutadien [MAK Value Documentation in German language, 2016]


Hartwig, A; MAK Commission; et al; Arand, Michael (2016). Hexachlorbutadien [MAK Value Documentation in German language, 2016]. The MAK Collection for Occupational Health and Safety, 1(2):1008-1052.

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated hexachlorobutadiene to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of hexachlorobutadiene is its toxicity and carcinogenicity in the kidney. In a 2‐year feeding study in rats, hexachlorobutadiene caused significantly increased incidences of adenomas and carcinomas of the kidneys only at the highest dose of 20 mg/kg bw, whereas nephrotoxicity was observed from 2 mg/kg bw. From the NOAEL of 0.2 mg/kg bw in this study, a MAK value of 0.02 ml/m3 is derived. As the critical effect is systemic, Peak Limitation Category II is assigned. The default excursion factor of 2 is set as no half‐life is known. Concerning the carcinogenicity of hexachlorobutadiene, the Commission concluded that a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK value is observed. Therefore, hexachlorobutadiene was assigned to Category 4 of carcinogenic substances. As the possible genotoxicity of hexachlorobutadiene is specific for the kidney and it has not been shown to reach the germ cells in an active form, hexachlorobutadiene is not classified in any of the categories for germ cell mutagens. The difference between the NOAEL for developmental toxicity in rats of 10 ml/m3 and the MAK value is sufficiently large, so that damage to the embryo or foetus is unlikely when the MAK value is observed. Thus, the substance is classified in Pregnancy Risk Group C. Skin contact may contribute significantly to systemic toxicity and hexachlorobutadiene continues to be 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 hexachlorobutadiene to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of hexachlorobutadiene is its toxicity and carcinogenicity in the kidney. In a 2‐year feeding study in rats, hexachlorobutadiene caused significantly increased incidences of adenomas and carcinomas of the kidneys only at the highest dose of 20 mg/kg bw, whereas nephrotoxicity was observed from 2 mg/kg bw. From the NOAEL of 0.2 mg/kg bw in this study, a MAK value of 0.02 ml/m3 is derived. As the critical effect is systemic, Peak Limitation Category II is assigned. The default excursion factor of 2 is set as no half‐life is known. Concerning the carcinogenicity of hexachlorobutadiene, the Commission concluded that a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK value is observed. Therefore, hexachlorobutadiene was assigned to Category 4 of carcinogenic substances. As the possible genotoxicity of hexachlorobutadiene is specific for the kidney and it has not been shown to reach the germ cells in an active form, hexachlorobutadiene is not classified in any of the categories for germ cell mutagens. The difference between the NOAEL for developmental toxicity in rats of 10 ml/m3 and the MAK value is sufficiently large, so that damage to the embryo or foetus is unlikely when the MAK value is observed. Thus, the substance is classified in Pregnancy Risk Group C. Skin contact may contribute significantly to systemic toxicity and hexachlorobutadiene continues to be designated with an “H” notation. Sensitization is not expected from the limited data.

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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:German
Date:27 April 2016
Deposited On:18 Oct 2019 08:53
Last Modified:18 Oct 2019 08:53
Publisher:Wiley-VCH Verlag
ISSN:2509-2383
ISBN:9783527600410
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/3527600418.mb8768d0060

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