Can acute dermal systemic toxicity tests be replaced with oral tests? A comparison of route-specific systemic toxicity and hazard classifications under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)

Regul Toxicol Pharmacol. 2013 Jun;66(1):30-7. doi: 10.1016/j.yrtph.2013.02.005. Epub 2013 Feb 24.

Abstract

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification criteria to determine the dermal classification reduced the concordance to 15% and the relative 'under-classification' to 1%, but increased the relative 'over-classification' to 84%. Both under- and over-classification are undesirable, and mitigation strategies are discussed. Finally, no substance with an oral LD50 of >2000mg/kg was classified for acute systemic toxicity by the dermal route, suggesting that dermal testing for acute systemic toxicity of such substances adds nothing to the hazard characterisation and should be removed from routine regulatory data requirements.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Databases, Factual
  • Hazardous Substances / administration & dosage
  • Hazardous Substances / classification
  • Hazardous Substances / toxicity*
  • Humans
  • Lethal Dose 50
  • Rats
  • Skin Tests / methods*
  • Toxicity Tests, Acute / methods*

Substances

  • Hazardous Substances