What determines skin sensitization potency-myths, maybes and realities. Part 1. The 500 molecular weight cut-off

BACKGROUND: It is widely accepted that there is a molecular weight (MW) cut-off of 500, such that single chemicals with MWs higher than 500 cannot be skin sensitizers. If true, this could serve as a useful principle for designing non-sensitizing chemicals. OBJECTIVES: To assess whether the 500 MW cut-off is a myth or a reality. METHODS: A database of 699 chemicals tested for skin sensitization in guinea pigs or mice was analysed to establish the number of tested chemicals with MW> 500, and to establish whether any of these were sensitizers. RESULTS: Only 13 (2%) of the 699 chemicals in the database have MW> 500. Of the 13 tested compounds with MW> 500 in the database, five are sensitizers and eight are non-sensitizers. CONCLUSIONS: The 500 MW cut-off for skin sensitization is a myth, probably derived from the widespread misconception that ability to efficiently penetrate the stratum corneum is a key determinant of sensitization potency. The scarcity of sensitizers with MW> 500 simply reflects the general scarcity of chemicals with MW> 500.