Does industry take the susceptible subpopulation of asthmatic individuals into consideration when setting derived no-effect levels?
Asthma, a chronic respiratory disease, can be aggravated by exposure to certain chemical irritants. The objectives were first to investigate the extent to which experimental observations on asthmatic subjects are taken into consideration in connection with the registration process under the EU REACH regulation, and second, to determine whether asthmatics are provided adequate protection by the derived no-effect levels (DNELs) for acute inhalation exposure. We identified substances for which experimental data on the pulmonary functions of asthmatics exposed to chemicals under controlled conditions are available. The effect concentrations were then compared with DNELs and other guideline and limit values. As of April 2015, only 2.6% of 269 classified irritants had available experimental data on asthmatics. Fourteen of the 22 identified substances with available data were fully registered under REACH and we retrieved 114 reliable studies related to these. Sixty-three of these studies, involving nine of the 14 substances, were cited by the REACH registrants. However, only 17 of the 114 studies, involving four substances, were regarded as key studies. Furthermore, many of the DNELs for acute inhalation were higher than estimated effect levels for asthmatics, i.e., lowest observed adverse effect concentrations or no-observed adverse effect concentrations, indicating low or no safety margin. We conclude that REACH registrants tend to disregard findings on asthmatics when deriving these DNELs. In addition, we found examples of DNELs, particularly among those derived for workers, which likely do not provide adequate protection for asthmatics. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd.
Unit of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Mia K V
MK
Johansson
Unit of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Gunnar
G
Johanson
Unit of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Swedish Toxicology Sciences Research Center (Swetox), Södertälje, Sweden.
Mattias
M
Öberg
Unit of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. linda.schenk@ki.se.|Department of Philosophy and History, Royal Institute of Technology, Stockholm, Sweden. linda.schenk@ki.se.
Linda
L
Schenk
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D001249:Asthma / Q000139:chemically induced*; D005062:European Union; D033161:Government Regulation; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis* / Q000331:legislation & jurisprudence / Q000592:standards; D008452:Maximum Allowable Concentration; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure / Q000032:analysis* / Q000331:legislation & jurisprudence / Q000592:standards; D016272:Occupational Health / Q000331:legislation & jurisprudence* / Q000592:standards; D020711:Threshold Limit Values; D017132:Workplace / Q000592:standards
D000395:Air Pollutants, Occupational
EU; REACH; SCOEL; asthma; chemicals regulation; guideline values; inhalation; policy; risk assessment