RESUMEN
This work attempts to evaluate dermal exposure (DE) of farm workers to dimethoate after 4 h of routine application to a lemon plantation. Dimethoate was measured on the workers' clothes as well as in stratum corneum (SC) and in saliva. In vitro permeation tests (IVPT) were performed through rat, pig and human skin and pig buccal, esophageal and sublingual mucosas. The mean of dimethoate DE was 342.19 ± 487.14 mg/d, the percentage of toxic dose per hour was higher than the other pesticides, and the SC penetration factors ranged between 0.5 and 14.81 and 0.05-53.96 % for back of neck and arms respectively. In the supporting IVPT study, dimethoate absorption through human skin was 14.75 % and the default value in the absence of experimental data for this product is 70%. These results show that in family farming the deficiency of correct clothing during the application of pesticides leaves workers more vulnerable.
Asunto(s)
Plaguicidas , Absorción Cutánea , Agricultura , Animales , Dimetoato/toxicidad , Humanos , Plaguicidas/metabolismo , Ratas , Piel/metabolismo , PorcinosRESUMEN
Abstract Bioequivalence (BE) assessment of topical drug products is a long-standing challenge. Agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published several drafts in recent years suggesting different approaches as alternative to evaluate the BE. A proposed Topical Classification System (TCS) has even been discussed. Given the above, the objective of this research was to use in vitro and in vivo BE approaches to evaluate Brazilian marketed mupirocin (MPC) ointments, previously classified as TCS class The in vitro permeation test (IVPT) was performed by applying formulations to pig skin by Franz cells. The in vivo methodology was dermatopharmacokinetic (DPK). These approaches (in vivo tape stripping and IVPT) demonstrated capability of distinguishing among different formulations, thus making them useful methodologies for BE evaluation.