RESUMEN
Pesticides must not pose unacceptable risks to human health, so risk assessments are conducted before products are authorised. Dermal exposure is often the main route of intake, so estimating realistic and trustworthy dermal absorption values is crucial for risk assessment. Although there are agreed test guidelines for in vitro dermal absorption studies, not every product is tested due to cost reasons. The present dataset consists of 945 individual in vitro experiments on the dermal absorption of human skin with 179 active substances of pesticides in 353 different mixtures, including concentrates and dilutions. The dataset was evaluated to identify the possible impacts of experimental conditions and physico-chemical properties on dermal absorption. The dataset was also analysed to assess the appropriateness of the pro rata correction for untested dilutions, and the set concentration cut-off to decide on the dilution status for choosing a default value on dermal absorption. The study found that the implementation of specific guidelines improved the harmonisation of study conduct, with support for approaches such as pro rata correction and default values. Further analysis of the specific co-formulants may identify influencing factors that may be more important than the experimental variables.
RESUMEN
This guidance on the assessment of dermal absorption has been developed to assist notifiers, users of test facilities and Member State authorities on critical aspects related to the setting of dermal absorption values to be used in risk assessments of active substances in Plant Protection Products (PPPs). It is based on the 'scientific opinion on the science behind the revision of the guidance document on dermal absorption' issued in 2011 by the EFSA Panel on Plant Protection Products and their Residues (PPR). The guidance refers to the EFSA PPR opinion in many instances. In addition, the first version of this guidance, issued in 2012 by the EFSA PPR Panel, has been revised in 2017 on the basis of new available data on human in vitro dermal absorption for PPPs and wherever clarifications were needed. Basic details of experimental design, available in the respective test guidelines and accompanying guidance for the conduct of studies, have not been addressed but recommendations specific to performing and interpreting dermal absorption studies with PPPs are given. Issues discussed include a brief description of the skin and its properties affecting dermal absorption. To facilitate use of the guidance, flow charts are included. Guidance is also provided, for example, when there are no data on dermal absorption for the product under evaluation. Elements for a tiered approach are presented including use of default values, data on closely related products, in vitro studies with human skin (regarded to provide the best estimate), data from experimental animals (rats) in vitro and in vivo, and the so called 'triple pack' approach. Various elements of study design and reporting that reduce experimental variation and aid consistent interpretation are presented. A proposal for reporting data for assessment reports is also provided. The issue of nanoparticles in PPPs is not addressed. Data from volunteer studies have not been discussed since their use is not allowed in EU for risk assessment of PPPs.
RESUMEN
The degradation of the natural estrogen 17ß-estradiol and the synthetic steroid hormone 17α-ethinylestradiol, two estrogens already detected in surface waters at low concentration levels, was investigated using continuous flow biofilm reactors and batch experiments. Biofilms in continuous flow experiments were created by natural organisms from river systems of the national park Unteres Odertal, Germany, whereas batch experiments were performed with isolated bacterial strains derived from biofilms. The analytical method, including solid phase extraction, silylation of analytes and measurement with GC/MS, was optimised for the target compounds 17ß-estradiol, 17α-ethinylestradiol and the possible metabolites estrone and estriol. The performance characteristics of the analytical method, namely recovery, standard deviations, method detection limits (MDL) and method quantification limits (MQL), were evaluated for accurate interpretation of degradation experiments. Continuous flow biofilm reactors were operated with two different nutrient media under dosage of estradiol and ethinylestradiol. Both estrogens were rapidly degraded within several hours; the metabolite estrone (from estradiol as well as from ethinylestradiol) was detected in significant amounts and was further decomposed. In additional batch experiments using isolated bacterial strains from the natural biofilms to decompose estradiol and ethinylestradiol, different metabolisms of isolates were explored. Five of the 15 isolated bacterial strains tested degraded estradiol and ethinylestradiol with different degradation rates. The results suggest that biofilms from national park Unteres Odertal possess a high capability to aerobically decompose natural and also synthetic estrogens so that these microorganisms could provide enhanced removal of pollutants in municipal water treatment plants.
Asunto(s)
Biopelículas/crecimiento & desarrollo , Reactores Biológicos/microbiología , Estrógenos/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Estradiol/análisis , Estradiol/metabolismo , Estrógenos/análisis , Estrona/análisis , Estrona/metabolismoRESUMEN
The degradation of the pharmaceuticals phenazone and metamizole, two pyrazolone-derivates in widespread use, using biofilms created by natural organisms from the national park Unteres Odertal, Germany, were investigated. An analytical method based on LC-MS/MS was optimised to determine the substances phenazone and methylaminoantipyrine (MAA), the hydrolysis product of metamizole (also known as dipyrone), as well as their metabolites 1,5-dimethyl-1,2-dehydro-3-pyrazolone (DP), acetaminoantipyrine (AAA), formylaminoantipyrine (FAA) and 4-aminoantipyrine (AA). Performance characteristics of the method were evaluated in terms of recovery, standard deviation, coefficient of variation, method detection limits (MDL) and method quantification limits (MQL). Degradation studies of phenazone and MAA were conducted using a laboratory-scale continuous flow biofilm reactor fed with different nutrient media and with variable hydraulic retention times of 24 and 32 h. MAA was degraded rapidly to FAA and AA, while phenazone was not degraded under the prevailing conditions even after 32 h. By operating the bioreactor in batch mode to study the phenazone degradation potential of the biofilm under limiting nutrient conditions, an elimination rate of 85% phenazone was observed, but because of the slow elimination rate and aerobic conditions, the metabolite DP was not detected. In additional batch experiments using bacterial isolates from the natural biofilm to decompose phenazone, some bacterial strains were able to form DP from phenazone in marginal concentrations over the sampling period of eight weeks. Obviously, the microorganisms need a reasonably long time to adapt their metabolisms to enable the removal of phenazone from water samples.