Dermal Absorption Read-Across for Agrochemicals: A Case Study with Triclopyr Formulations Using In Vitro Human Studies

Abstract

Dermal absorption data are required on agrochemical formulations to conduct risk assessments for subpopulations who may be exposed dermally to the formulation and/or its spray dilution, for example, operators/sprayers, bystanders (incidental and residential), and re-entry workers. In the absence of formulation-specific data, the European Food Safety Authority (EFSA) guidance proposes highly conservative default values and very limited opportunities for read-across to existing data. In this case study, data from GLP and OECD 428 test guideline-compliant in vitro dermal absorption studies using human skin for 5 formulations containing triclopyr-butoxyethyl ester (BEE) were analyzed to develop triclopyr-specific read-across approach. Four emulsifiable concentrate and one emulsion-in-water formulations were tested as “concentrates” (undiluted product; concentration range was 90–240 gacidequivalent(a.e.)/L) and/or as 1 or 2 representative “spray dilutions” (product diluted with water; concentration range was 0.3–10.3 g(a.e.)/L). Worst-case dermal absorption values (according to EFSA guidance calculations) ranged between 1% and 4% for the concentrates and 8% and 20% for the spray dilutions. Increases in percentage dermal absorption were seen with decreased triclopyr-BEE concentration, but these were not linear. Logarithmic functions describe the absorption trend with concentration for the concentrates (R2=0.8505), spray dilutions (R2=0.7993), or both (R2=0.9439). Human in vivo dermal absorption data available for one of the above formulations showed consistency with the in vitro data. This case study demonstrates that an existing dataset for an active substance may be used for read-across purposes for an untested formulation as an alternative approach to testing.