Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

This paper reviews key elements in the assessment of human health effects from combined exposure to multiple chemicals taking into consideration current knowledge and challenges to identify areas where scientific advancement is mostly needed and proposes a decision-making scheme on the basis of existing methods and tools. The assumption of dose addition and estimation of the hazard index (HI) is considered as a starting point in component-based risk assessments. When, based on the generic HI approach, an unacceptable risk is identified, more specific risk assessment options may be implemented sequentially or in parallel depending on problem formulation, characteristics of the chemical group under assessment, exposure levels, data availability and resources. For prospective risk assessments, the reference point index/margin of exposure (RPI/MOET) (Option 1) or modified RPI/normalized MOET (mRPI/nMOET) (Option 2) approaches may be implemented focusing on the specific mixture effect. Relative potency factors (RPFs) may also be used in the RPI approach since a common uncertainty factor for each mixture component is introduced in the assessment. Increased specificity in the risk assessment may also be achieved when exposure of selected population groups is considered (Option 3/exposure). For retrospective risk assessments, human biomonitoring data available for vulnerable population groups (Option 3/susceptibility) may present more focused scenarios for consideration in human health risk management decisions. In data-poor situations, the option of using the mixture assessment factor (MAF) is proposed (Option 4), where an additional uncertainty factor is applied on each mixture component prior to estimating the HI. The magnitude of the MAF may be determined by the number of mixture components, their individual potencies and their proportions in the mixture, as previously reported. It is acknowledged that implementation of currently available methods and tools for human health risk assessment from combined exposure to multiple chemicals by risk assessors will be enhanced by ongoing scientific developments on new approach methodologies (NAMs), integrated approaches to testing and assessment (IATA), uncertainty analysis tools, data sharing platforms, risk assessment software as well as guideline development to meet legislative requirements.

In the frame of a “greener agriculture”, the development of new natural pesticides that are safer than their synthetic counterparts is gaining ground. Nonetheless, the origin of their nature does not necessarily imply their eco-friendliness. Hence, specific ecotoxicological studies are needed, with products being subjected to hazard and consequent risk assessment, for registration purposes. We have previously described on the strong nematicidal activity of Melia azedarach (chinaberry), Petroselinum crispum (parsley) and Eruca sativa (rocket) against the nematode Meloidogyne incognita. With this study the effect of the above-mentioned nematicidal botanicals on Eisenia fetida, Enchytraeus albidus, Daphnia magna and Danio rerio (Zebrafish) is reported, being all model organisms for the study of ecotoxicology of pesticides under registration. The implemented protocols are according to the OECD standards used for the evaluation of formulates under authorization. NOEC values were estimated to be higher than the highest concentrations assessed as recommended by OECD guidelines (≥1000 mg test item/kg dry soil). According to the presented results, all tested botanical nematicidals proved ecofriendly, not hindering the reproduction of juvenile worms of Eisenia fetida, and Enchytraeus albidus. Notably, Petroselinum crispum exhibited beneficial effects on reproduction of Eisenia fetida, as the number of juveniles increased. M. azedarach extract demonstrated moderate toxicity to zebrafish embryos (LC₅₀ was 51.41 ± 1.67 mg/L), yet it did not elicit adverse effects on the zebrafish liver. Thus, chinaberry, parsley and rocket are promising to be developed into new “green” nematicides.