Comparison of the acceptable surface limits derived from the skin sensitization potency for workers and swab residue limits determined from the permitted daily exposure derived from the systemic effects

抄録

Allergic contact dermatitis is a common occupational and environmental health problem and setting of health-based exposure limits (HBELs) to prevent induction of skin sensitization is strongly desired. When manufacturing pharmaceuticals in a shared facility, cleaning validation using surface residue levels (SRLs) derived from permitted daily exposures (PDEs) is conducted to avoid cross-contamination from the perspective of protecting patients; however, it is unclear whether the SRLs are sufficient to prevent induction of skin sensitization for workers as well. In this study, we compared acceptable surface limits (ASLs) derived from acceptable exposure levels (AELs) based on EC1.6 obtained from local lymph node assay (LLNA): BrdU-ELISA for occupational risk management of skin sensitizers with PDE-based SRLs. ASLs for 1,4-phenylenediamine (GHS skin sensitization sub-category 1A), isoeugenol (sub-category 1A), and methyl methacrylate (sub-category 1B) were compared with SRLs based on the PDEs derived from their systemic effects. The results yielded an SRL for 1,4-phenylenediamine (PDE: 0.8 mg/day) of 30 mg/100 cm², almost 1,000 times higher than ASL (0.031 mg/100 cm²) derived from its skin sensitization potency. SRL for isoeugenol (PDE: 3.1 mg/day) was 130 mg/100 cm², over 500 times higher than ASL (0.18 mg/100 cm²). For methyl methacrylate (PDE: 5 mg/day) as well, SRL (200 mg/100 cm²) was higher, but it was within 20 times the ASL (10 mg/100 cm²). These results showed that ASL-based risk management is extremely important especially for strong sensitizers classified as GHS sub-category 1A for occupational skin sensitization risk management.