Endocrine Disruption: Current approaches for regulatory testing and assessment of plant protection products are fit for purpose

Abstract

The ongoing debate concerning the regulation of endocrine disruptors, has increasingly led to questions concerning the current testing of chemicals and whether this is adequate for the assessment of potential endocrine disrupting effects. This paper describes the current testing approaches for plant protection product (PPP) active substances in the European Union and the United States and how they relate to the assessment of endocrine disrupting properties for human and environmental health. This includes a discussion of whether the current testing approaches cover modalities other than the estrogen, androgen, thyroid and steroidogenesis (EATS) pathways, sensitive windows of exposure, adequate assessment of human endocrine disorders and wildlife species, and the determination of thresholds for endocrine disruption. It is concluded, that the scope and nature of the core and triggered data requirements for PPP active substances are scientifically robust to address adverse effects mediated through endocrine mode(s) of action and to characterise these effects in terms of dose response.

The effects on the endocrine system under hepatotoxicity induction by phenobarbital and di(2-ethylhexyl)phthalate in intact juvenile male rats

“…Many chemicals indirectly affect the endocrine system via lead (representative) toxicities such as hepatotoxicity, renal toxicity, and body weight loss (Kortenkamp et al, 2012). Toxicity studies in compliance with the US Environmental Pro-tection Agency (EPA) or Office of Economic Cooperation and Development (OECD) test guidelines provide scientific information regarding direct or indirect effects on the endocrine system (U.S. EPA, 2011; Day et al, 2018). Indirect effects that are non-specific secondary consequences of lead toxicity should not be considered when evaluating EDCs (Stump et al, 2014).…”

Thresholds of adversity and their applicability to endocrine disrupting chemicals

“…Also, it is noteworthy that all of these publications tend to portray endocrine disruption as a "special" form of toxicity and endocrinology as a "special" form of biology. The views put forward do not reflect the balance of the available evidence and contrast with mainstream scientific thinking (Rhomberg and Goodman 2012;Borgert et al 2013Borgert et al , 2018Dekant and Kehrer 2013;Testai et al 2013;Autrup et al 2015;Matthiessen et al 2017;Day et al 2018;Clahsen et al 2019).…”

Overview of the effects of chemical mixtures with endocrine disrupting activity in the context of real‑life risk simulation (RLRS): An integrative approach (Review)

“…Exposure to such substances is of particular concern in sensitive periods, such as the prenatal period, as these exposures can lead to irreversible changes in the developing organs and increase the susceptibility to develop diseases later in life. Nevertheless, there is still controversy concerning the possible role of exposure at real-life concentrations to environmental chemicals and certain endocrine-related human diseases, such as hormone-related cancers, reproductive disorders, obesity, diabetes and neurodevelopment disorders (20). Certainly, EDs interfere with brain development through changes in thyroid hormone levels that are essential for the development of the nervous system.…”

“…Existing assays are currently focused on the estrogen, androgen, thyroid and steroidogenesis (EATS) pathways and less on non-EATS modalities. However, standard chronic apical toxicity tests are capable of detecting most downstream effects of perturbation of the non-EATS pathways (20).…”