Assessment of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption.
Dermal absorption is an integral part of non-dietary human safety risk assessments for agrochemicals. Typically, dermal absorption data for agrochemical active substances are generated from the undiluted formulation concentrate and its spray dilutions. European Food Safety Authority (EFSA) guidance, which combines highly conservative default values, very limited opportunities for read-across from existing data and other overly conservative conclusions, was the driver for this assessment. To investigate the reliability of the EFSA guidance, a homogeneous data-set of 190 GLP and OECD guideline compliant in vitro human skin studies, chosen to match the test method preferred by EU data requirements, was evaluated. These studies represented a wide range of active substances, formulation types, and concentrations. In alignment with EFSA guidance on human exposure assessment, a conservative estimate of absorption (95th percentile) was chosen to define defaults, which were also based on the EFSA worst-case assumption that all material in skin, excluding the first two tape strips, is absorbed. The analysis supports dermal absorption defaults of 6% for liquid concentrates, 2% for solid concentrates, and 30% for all spray dilutions, irrespective of the active substance concentration. Relatively high dermal absorption values for organic solvent-based formulations, compared to water-based or solid concentrates, support their use as worst-case surrogate data for read-across to other formulation types. The current review also shows that dermal absorption of sprays does not increase linearly with increasing dilution, and provides a novel, science-based option for extrapolation from existing data.
Dow AgroSciences Ltd., 3B Park Square, Milton Park, Abingdon, OX14 4RN Oxfordshire, UK. Electronic address: maggarwal@dow.com.
M
M
Aggarwal
E. I. du Pont de Nemours and Company, DuPont Crop Protection, Stine-Haskell Research Center, P.O. Box 30, Newark, Delaware 19714-0030, USA.
M
M
Battalora
Bayer SAS, Bayer CropScience, 355 rue dostoievski, CS 90153 Valbonne, 06906 Sophia Antipolis, France.
P
P
Fisher
Dr. Knoell Consult GmbH, 8 Marie-Curie Street, Leverkusen, 51377, Germany.
A
A
Hüser
Syngenta Ltd., Bracknell, Berkshire, RG42 6EY, UK.
R
R
Parr-Dobrzanski
DuPont de Nemours GmbH Deutschland, 173-175 Hugenottenallee, Neu-Isenburg 63263, Germany.
M
M
Soufi
Dr. Knoell Consult GmbH, 8 Marie-Curie Street, Leverkusen, 51377, Germany.
V
V
Mostert
Makhteshim Agan Europe, Makhteshim Agan Holding B.V., Schaffhausen, Switzerland.
C
C
Strupp
Syngenta Ltd., Bracknell, Berkshire, RG42 6EY, UK.
P
P
Whalley
BASF Oesterreich GmbH, Millennium Tower, 25, Handelskai 94-96, Wien 1200, Austria.
C
C
Wiemann
Dow AgroSciences Ltd., 3B Park Square, Milton Park, Abingdon, OX14 4RN Oxfordshire, UK.
R
R
Billington
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D010575:Pesticides / Q000493:pharmacokinetics*; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
D010575:Pesticides
Agrochemicals; Dermal absorption; Human skin; In vitro; Pesticides; Plant protection products