title: Classification of dermal sensitizers in pharmaceutical manufacturing.
abstract: Workers in development and manufacturing of pharmaceuticals are at risk for occupational contact dermatitis (OCD) of irritative (ICD) or allergic (ACD) origin, due to contacts with reactive intermediates (IM) and drug substances (DS). We examined, if alternative methods could replace presently used animal tests for identification of ACD in pharmaceutical development and manufacturing, without apparent loss of worker health, in line with regulations. The status of alternative methods for regulatory toxicology for consumer products has recently been reviewed by the Organisation for Economic Co-operation and Development (OECD) and the European Commission's Joint Research Center (JRC) for the European Chemicals Agency (ECHA). They concluded that prediction of skin sensitization potential, extent and quality by in vitro methods, for regulatory assessments, will depend on the regulatory purpose and level of confidence required. Some alternative methods are currently in validation. Current Globally Harmonized System (GHS) regulations on classification, labeling and packaging of substances and mixtures depend on human and animal data, whereas alternative methods may provide supportive evidence. Since the levels of workplace skin exposure to DS and IM in manufacturing of pharmaceuticals are usually not known, it is not possible to conduct quantitative risk assessments based on threshold calculations for contact sensitizers.
authors.affiliation: Novartis Pharma AG NIBR, Postfach, CH-4002 Basel, Switzerland. Electronic address: gian_christian.winkler@novartis.com.
authors.forename: Gian C
authors.initials: GC
authors.lastname: Winkler
authors.affiliation: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080, USA. Electronic address: christopher.perino@novartis.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Perino
authors.affiliation: University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Electronic address: selene.araya@unibas.ch.
authors.forename: Selene H
authors.initials: SH
authors.lastname: Araya
authors.affiliation: Bechter Consulting GmbH, Stadtweg 37, CH-4310 Rheinfelden, Switzerland. Electronic address: rudolf@bechter.ch.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bechter
authors.affiliation: Novartis International AG, Postfach, CH-4002 Basel, Switzerland. Electronic address: martin.kuster@novartis.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuster
authors.affiliation: Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland. Electronic address: ester.lovsin_barle@novartis.com.
authors.forename: Ester
authors.initials: E
authors.lastname: Lovsin Barle
mesh_terms: D000485:Allergens / Q000145:classification* / Q000633:toxicity; D000818:Animals; D003257:Consumer Product Safety; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D004345:Drug Industry / Q000331:legislation & jurisprudence; D064420:Drug-Related Side Effects and Adverse Reactions; D033161:Government Regulation; D006801:Humans; D016273:Occupational Exposure; D016272:Occupational Health; D018570:Risk Assessment / Q000331:legislation & jurisprudence / Q000379:methods; D012867:Skin; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000485:Allergens
keywords: Classification; Contact sensitizer; Drug development; Drug research; Occupational contact dermatitis; Occupational health; Pharmaceutical manufacturing; Quantitative risk assessment; Worker safety