Publikation:
Risk assessment for irritating chemicals - derivation of extrapolation factors

Kurzanzeige
dc.contributor.authorMangelsdorf, Inge
dc.contributor.authorSchröder, Katrin
dc.contributor.authorEscher, Sylvia E.
dc.contributor.authorKolossa-Gehring, Marike
dc.contributor.authorDebiak, Malgorzata
dc.date.accessioned2024-06-16T13:52:32Z
dc.date.available2024-06-16T13:52:32Z
dc.date.issued2021
dc.description.abstractIrritation of the eyes and the upper respiratory tract are important endpoints for setting guide values for chemicals. To optimize the use of the often-limited data, we analysed controlled human exposure studies (CHS) with 1-4 h inhalation of the test substance, repeated dose inhalation studies in rodents, and Alarie-Tests and derived extrapolation factors (EF) for exposure duration, inter- and intraspecies differences. For the endpoint irritating effects in the respiratory tract in rodents, geometric mean (GM) values of 1.9 were obtained for the EF for subacute ->subchronic (n = 16), 2.1 for subchronic -> chronic (n = 40), and 2.9 for subacute -> chronic (n = 10) extrapolation. Based on these data we suggest an EF of 2 for subchronic -> chronic and of 4 for subacute -> chronic extrapolation. In CHS, exposure concentration determines the effects rather than exposure duration. Slight reversible effects during 4 h exposure indicate that an EF of 1 can be considered for assessing chronic exposures. To assess species extrapolation, 10 chemicals were identified with both, reliable rat inhalation studies and CHS. The GM of the ratio between the No Observed Adverse Effect Concentration (NOAEC) in rats and humans was 2.3 and increased to 3.6 when expanding the dataset to all available EF (n = 25). Based on these analyses, an EF of 3 is suggested to extrapolate from a NOAEC in a chronic rat study to a NOAEC in a CHS. The analysis of EFs for the extrapolation from a 50% decrease in respiratory frequency in the Alarie test in mice (RD50) to a NOAEC in a CHS resulted in a GM of 40, for both, the reliable (n = 11) and the overall dataset (n = 19). We propose to use the RD50 from the Alarie test for setting guide values and to use 40 as EF. Efs for intraspecies differences in the human population must account for susceptible persons, most importantly for persons with chemical intolerance (CI), who show subjective signs of irritation at low concentrations. The limited data available do not justify to deviate from an EF of 10 - 20 as currently used in different regulatory settings. © 2020 The Authors.en
dc.format.extent1 Onlineressource (9 pages)
dc.format.mediumonline resource
dc.identifier.doihttps://doi.org/10.60810/openumwelt-715
dc.identifier.urihttps://openumwelt.de/handle/123456789/3765
dc.language.isoeng
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectInnenraumluft
dc.subjectDatenextrapolation
dc.subjectRisikoanalyse
dc.titleRisk assessment for irritating chemicals - derivation of extrapolation factors
dc.title.alternativeRisk assessment for irritating chemicals - derivation of extrapolation factors
dc.typeWissenschaftlicher Artikel
dc.type.dcmitext
dc.type.mediumcomputer
dspace.entity.typePublication
local.bibliographicCitation.journalTitleInternational Journal of Hygiene and Environmental Health
local.bibliographicCitation.originalDOI10.1016/j.ijheh.2020.113668
local.bibliographicCitation.volume232 (2021)
local.collectionAufsätze
local.contributor.authorId02057506
local.contributor.authorId02101105
local.contributor.authorId02186630
local.contributor.authorId02163691
local.identifier.catalogId02481130
local.ingest.leader06343naa a2200000uu 4500
local.jointTitleRISK ASSESSMENT FOR IRRITATING CHEMICALS DERIVATION OF EXTRAPOLATION FACTORS
local.reviewtrue
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local.staffPublicationtrue
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relation.isAuthorOfPublication.latestForDiscovery0c3b6c3e-eff4-42d8-94e9-07a4fee4049c
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