In 2014, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK value) of dichloromethane [75-09-2] and set a MAK value of 50 ml dichloromethane/m3 (180  mg/m3). In humans, exposure to 50  ml/m3 of dichloromethane led to CO-Hb levels in the range of 3%, which is above the endogenous CO-Hb range of 0.4–2.6% in non-smoking pregnant women. There is no information available on the CO-Hb level at which oxygen deficiency occurs in the foetal tissues. As a result, the possibility of prenatal toxicity cannot be excluded even if the MAK value of 50 ml dichloromethane/m3 is observed. Based on thisfinding, classification in Pregnancy Risk Group B has been confirmed. In 2015, the biological tolerance value (BAT value) of 500 μg dichloromethane/l blood was derived in correlation to the MAK value. Pregnancy Risk Group B istherefore also valid forthe BAT value. The possibility of prenatal toxicity cannot be excluded even when adhering to the BAT value of 500 μg dichloromethane/l bloo

Arand, Michael

Drexler, H

Hartwig, A

MAK Commission

Michaelsen, S

Schriever-Schwemmer, G

Weistenhöfer, W

English

ZORA

Zurich Open Repository andArchiveUniversity of ZurichUniversity LibraryStrickhofstrasse 39CH-8057 Zurichwww.zora.uzh.chYear: 2023Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BATvalueWeistenhöfer, W ; Michaelsen, S ; Schriever-Schwemmer, G ; Drexler, H ; Hartwig, A ; MAK Commission ;Arand, MichaelDOI: https://doi.org/10.34865/bb7509e8_3adPosted at the Zurich Open Repository and Archive, University of ZurichZORA URL: https://doi.org/10.5167/uzh-256114Journal ArticlePublished Version  The following work is licensed under a Creative Commons: Attribution 4.0 International (CC BY 4.0) License.Originally published at:Weistenhöfer, W; Michaelsen, S; Schriever-Schwemmer, G; Drexler, H; Hartwig, A; MAK Commission; Arand,Michael (2023). Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BAT value. TheMAK Collection for Occupational Health and Safety, 8(3):Doc068.DOI: https://doi.org/10.34865/bb7509e8_3adKeywordsdichloromethane; biological tolerance value; BAT value; developmental toxicity; prenatal toxicity; pregnancy risk groupCitation Note:Weistenhöfer W, Michaelsen S, Schriever-Schwemmer G, Drexler H, Hartwig A, MAK Commission. Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BAT value. Assessment Values in Biological Material – Translation of the German version from 2023. MAK Collect Occup Health Saf. 2023 Sep;8(3):Doc068. https://doi.org/10.34865/bb7509e8_3adManuscript completed:21 Sep 2022Publication date:29 Sep 2023License: This work is licensed under a Creative Commons Attribution 4.0 International License.Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BAT valueAssessment Values in Biological Material – Translation of the German version from 2023W. Weistenhöfer1S. Michaelsen2G. Schriever-Schwemmer2H. Drexler3,*A. Hartwig4,*MAK Commission5,*1 Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute and Outpatient Clinic of Occupational, Social, and Environmental Medicine, Henkestraße 9–11, 91054 Erlangen, Germany2 Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany3 Head of the working group “Assessment Values in Biological Material” of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute and Outpatient Clinic of Occupational, Social, and Environmental Medicine, Henkestraße 9–11, 91054 Erlangen, Germany4 Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany5 Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany* email: H. Drexler (hans.drexler@fau.de), A. Hartwig (andrea.hartwig@kit.edu), MAK Commission (arbeitsstoffkommission@dfg.de)AbstractIn 2014, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re-evaluated the maximum workplace concentration (MAK  value) of dichloromethane [75-09-2] and set a MAK  value of 50  ml  dichloromethane/m3 (180  mg/m3). In humans, exposure to 50  ml/m3 of dichloromethane led to CO-Hb levels in the range of 3%, which is above the endogenous CO-Hb range of 0.4–2.6% in non-smoking pregnant women. There is no information available on the CO-Hb level at which oxygen deficiency occurs in the foetal tissues. As a result, the possibility of prenatal toxicity cannot be excluded even if the MAK value of 50 ml dichloromethane/m3 is observed. Based on this finding, classification in Pregnancy Risk Group B has been confirmed. In 2015, the biological tolerance value (BAT value) of 500 μg dichloromethane/l blood was derived in correlation to the MAK value. Pregnancy Risk Group B is therefore also valid for the BAT value. The possibility of prenatal toxicity cannot be excluded even when adhering to the BAT value of 500 μg dichloromethane/l blood.The MAK Collection for Occupational Health and Safety 2023, Vol 8, No 3 1Assessment Values in Biological Material – DichloromethaneBAT value (2015) 500 μg dichloromethane/l bloodSampling time: immediately after exposureMAK value (2014) 50 ml/m3 ≙ 180 mg/m3Peak limitation (2014) Category II, Excursion factor 2Absorption through the skin (2014) HCarcinogenicity (2014) Category 5Prenatal toxicity (2014) Group BIn 2014, a maximum workplace concentration (MAK value) of 50 ml/m3 (180 mg/m3) (due to neurotoxic effects and the formation of CO-Hb) as well as an assignment to Pregnancy Risk Group B was established for dichloromethane (translated in Hartwig and MAK Commission 2016). In humans, exposure to 50 ml dichloromethane/m3 leads to CO-Hb levels in the range of 3%. In 2015, a biological tolerance value (BAT value) of 500 μg dichloromethane/l blood was derived in correlation to the MAK value (translated in Bolt et al. 2018). When setting BAT values, as of 2019, the adoption of the pregnancy risk group valid for the respective MAK value is explicitly verified (DFG 2019). This addendum evaluates whether Pregnancy Risk Group B can similarly be adopted for the BAT value of dichloromethane.Prenatal toxicityHuman data have to be used when evaluating prenatal toxicity, as humans react more sensitively to neurotoxicity compared to animals, and, in terms of neurotoxicity, a foetus is at least as susceptible as an adult. Due to the insufficient data on developmental toxicity and developmental neurotoxicity in humans, dichloromethane would be assigned to Pregnancy Risk Group D.Carbon monoxide, which has been assigned to Pregnancy Risk Group B, is a metabolite of dichloromethane (translated in Henschler 1992). Endogenous formation of CO is increased by a factor of 1.5–3 in pregnant women compared to non-pregnant women. Non-smoking pregnant women have an average CO-Hb value of 0.4–2.6%, whereas this value is 0.4–1.1% in non-pregnant women (Longo 1970).Carbon monoxide can cross the placenta whereby increased CO-Hb levels and the resulting O2 deficiency may lead to such foetal effects as reduced birth weight and an increased heart rate. In equilibrium conditions, the proportion of CO-Hb in foetal blood is somewhat higher than that of the mother’s blood. The foetal CO-Hb value exhibits a delayed increase over several hours and is 10 to 15% higher than that of the mother (Astrup et al. 1972; Longo 1970). Since foetal effects above the maximum endogenous CO-Hb value for pregnant women (CO-Hb value up to 2.6%), even at exposures at the level of the MAK value of dichloromethane (CO-Hb value of 3%), could not be ruled out, dichloromethane like its metabolite carbon monoxide has been assigned to Pregnancy Risk Group B.Evaluation of a pregnancy risk group for the BAT valueWorkplace exposure to 50 ml dichloromethane/m3 leads to a CO-Hb value in the range of 3% (Soden et al. 1996), which is above the endogenous CO-Hb value of 0.4–2.6% in non-smoking pregnant women. Since no information is available as to which CO-Hb level results in oxygen deficiency in foetal tissues, the possibility of foetal effects cannot be excluded at a CO-Hb value of about 3%, and dichloromethane is therefore assigned to Pregnancy Risk Group B. As the BAT value for dichloromethane was derived in correlation to the MAK value of 50 ml dichloromethane/m3,the possibility of prenatal effects cannot be excludedby compliance with the BAT value of 500 μg dichloromethane/l blood.The MAK Collection for Occupational Health and Safety 2023, Vol 8, No 3 2Assessment Values in Biological Material – DichloromethaneSince the CO-Hb value itself is subject to variations and since exposures other than dichloromethane, such as smoking, may add to the CO-Hb level and cannot be controlled, the derivation of a NOAEC (no observed adverse effect concen-tration) for maternal CO-Hb entails too much uncertainty. For this reason, no information can be given on the prerequis-ite for classification in Pregnancy Risk Group C (Hartwig and MAK Commission 2016).NotesCompeting interestsThe established rules and measures of the Commission to avoid conflicts of interest (www.dfg.de/mak/conflicts_interest) ensure that the content and conclusions of the publication are strictly science-based.ReferencesAstrup P, Olsen HM, Trolle D, Kjeldsen K (1972) Effect of moderate carbon-monoxide exposure on fetal development. Lancet 300(7789): 1220–1222.https://doi.org/10.1016/s0140-6736(72)92270-2Bolt HM, Weistenhöfer W, Drexler H, Hartwig A, MAK Commission (2018) Addendum to dichloromethane. BAT Value Documentation, 2016. MAK Collect Occup Health Saf 3(4): 2050–2053. https://doi.org/10.1002/3527600418.bb7509e2218DFG (Deutsche Forschungsgemeinschaft), editor (2019) List of MAK and BAT Values 2019. Maximum Concentrations and Biological Tolerance Values at the Workplace. Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, report 55. Weinheim: Wiley-VCH. https://doi.org/10.1002/9783527826889Hartwig A, MAK Commission (2016) Dichloromethane. MAK Value Documentation, 2015. MAK Collect Occup Health Saf 1(3): 1704–1742.https://doi.org/10.1002/3527600418.mb7509e5916Henschler D, editor (1992) Carbon monoxide. MAK Value Documentation, 1981. In: Occupational Toxicants. Volume 4. Weinheim: VCH. p. 79–95. Also available from https://doi.org/10.1002/3527600418.mb63008e0004Longo LD (1970) Carbon monoxide in the pregnant mother and fetus and its exchange across the placenta. Ann N Y Acad Sci 174(1): 312–341.https://doi.org/10.1111/j.1749-6632.1970.tb49798.xSoden KJ, Marras G, Amsel J (1996) Carboxyhemoglobin levels in methylene chloride-exposed employees. J Occup Environ Med 38(4): 367–371.https://doi.org/10.1097/00043764-199604000-00014The MAK Collection for Occupational Health and Safety 2023, Vol 8, No 3 3

Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BAT value

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Dichloromethane – Addendum: evaluation of a pregnancy risk group for the BAT value

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