Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties

Abstract

Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.

Crop Protection Compounds: A Source of Endocrine Disruptors in Uruguay?

“…Whereas in relation to potentially endocrine disrupting compounds, six fungicides, five herbicides and five insecticides were identified. The analysis of effects on endocrine system was complemented with information from several scientific articles [9,10,[23][24][25][26] and according to the crop protection compound priorities are: acetochlor, chlorpyrifos methyl, mancozeb, metolachlor and tebuconazole ( Table 3).…”

“…Currently, more than 2 million hectares are destined to agriculture and approximately 50% correspond to soybean crops. In addition, the imported volumes of agrochemicals significatively increase, particularly herbicides (10,200,404 kg AI in 2017).…”

“…In the agricultural production, a wide variety of crop protection compounds are used and several of them may interfere with endocrine system functioning [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. According to Kavlock et al [16], an "endocrine disrupting compound" (EDC) is "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body, which are responsible for the maintenance of homeostasis, reproduction, development and or behavior."…”

Endocrine disruptors: strategies for determination and occurrence in marine environments

“…For instance, the herbicide diuron is capable of inhibiting the androgens (Thibaut & Porte, 2004) while the DDT metabolites mimic the action of estrogens (Bulayeva & Watson, 2004). However the possibilities and pathways of pesticides may cause disturbance in endocrine systems as well as their endpoints in individuals still is not well understood (Ventura et al, 2016;Monteagudo et al, 2016;Marx-Stoelting et al, 2014). PAHs are generated in the processes of incomplete combustion or pyrolysis of organic matter (e.g., coal, oil, gas and wood) and traditionally have been used as tracers of burning fuels Sun et al, 2013;Da Rocha, et al, 2009) and oil refineries (Bayat et al, 2015;Zrafi-nouira et al, 2010).…”

Science-based decision matrix for the identification of endocrine disruptors for regulatory purposes

“…Typical severe effects comprise (but are not limited to) tumours, irreversible forms of organ damage, malformations or infertility'' (Marx-Stoelting et al 2014). Effects described as severe would thus support categorisation into a higher category (cat 1 or 2) in the decision matrix, while effects described as mild or slight would support categorisation into a lower category (cat 2 or 3) in the decision matrix.…”