title: Cancer risk of immunosuppressants in manufacturing.
abstract: During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop. An internal workshop was conducted to compare several pharmaceutical substances with the intrinsic property to cause immunosuppression, with the attempt to define the risk of healthy employees to develop cancer due to exposure to immunosuppressive substance at work and to determine the appropriate hazard classification for regulatory purposes. Data are discussed with emphasis on cyclosporine to reason the dose-response relationship and the safe level for occupational exposure. Our review indicates that if the exposure to cyclosporine at the workplace is below the threshold necessary to induce immunosuppression, the risk to develop cancer is negligible. Non-mutagenic immunosuppressants do not contribute to malignancies in occupational setting if their air concentrations do not exceed the immunosuppressive threshold limited with occupational exposure limits (OELs), which is for cyclosporine 17.5μg/m(3).
authors.affiliation: Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland. Electronic address: ester.lovsin_barle@novartis.com.
authors.forename: Ester Lovsin
authors.initials: EL
authors.lastname: Barle
authors.affiliation: Novartis Pharma AG NIBR, Postfach, CH-4002 Basel, Switzerland. Electronic address: gian_christian.winkler@novartis.com.
authors.forename: Gian Christian
authors.initials: GC
authors.lastname: Winkler
authors.affiliation: Novartis Pharma AG NIBR, Postfach, CH-4002 Basel, Switzerland. Electronic address: peter.ulrich@novartis.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Ulrich
authors.affiliation: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, United States. Electronic address: christopher.perino@novartis.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Perino
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 NIBR, Postfach, CH-4002 Basel, Switzerland. Electronic address: alessandro.probst@novartis.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Probst
authors.affiliation: Novartis Tiergesundheit AG, CH-4002 Basel, Switzerland. Electronic address: silke.thielen@novartis.com.
authors.forename: Silke
authors.initials: S
authors.lastname: Thielen
authors.affiliation: Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland. Electronic address: rudolf.bechter@novartis.com.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bechter
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Cancer risk; Cyclosporine; Immunosuppression; Occupational exposure; Pharmaceutical production