Specific effects on the thyroid relevant for performing a dietary cumulative risk assessment of pesticide residues: 2024 update.

EFSA updated its previous work on the establishment of specific effects that are considered relevant for grouping pesticide residues targeting the thyroid and for performing the retrospective assessment of dietary cumulative risk (CRA). The two specific effects already selected in 2019 leading to the two cumulative assessment groups (CAGs) 'hypothyroidism' and 'C-cell hypertrophy, hyperplasia and neoplasia' were reconfirmed. Compared to 2019, the list of indicators that can be used to identify these specific effects was refined to only include histopathological changes. In a second phase of the work, data will be extracted on indicators of the specific effects from the dossiers on active substances (a.s.) used as plant protection products. The criteria for including a.s. into CAGs were also updated, together with the hazard characterisation methodology and the lines of evidence for assessing CAG-membership probabilities. The tasks related to the data extraction and the establishment of the CAGs on hypothyroidism and on C-cell hypertrophy, hyperplasia and neoplasia are beyond the scope of this report. This part of the CRA process has been outsourced and will be the subject of a separate report.

Retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides.

EFSA established cumulative assessment groups and conducted retrospective cumulative risk assessments for two types of craniofacial alterations (alterations due to abnormal skeletal development, head soft tissue alterations and brain neural tube defects) for 14 European populations of women in childbearing age. Cumulative acute exposure calculations were performed by probabilistic modelling using monitoring data collected by Member States in 2017, 2018 and 2019. A rigorous uncertainty analysis was performed using expert knowledge elicitation. Considering all sources of uncertainty, their dependencies and differences between populations, it was concluded with varying degrees of certainty that the MOET resulting from cumulative exposure is above 100 for the two types of craniofacial alterations. The threshold for regulatory consideration established by risk managers is therefore not exceeded. Considering the severity of the effects under consideration, it was also assessed whether the MOET is above 500. This was the case with varying levels of certainty for the head soft tissue alterations and brain neural tube defects. However, for the alterations due to abnormal skeletal development, it was found about as likely as not that the MOET is above 500 in most populations. For two populations, it was even found more likely that the MOET is below 500. These results were discussed in the light of the conservatism of the methodological approach.

Health effects of living near an incinerator: A systematic review of epidemiological studies, with focus on last generation plants.

Huge reductions in incinerators' emissions occurred over time, and results of older studies cannot be directly generalized to modern plants. We conducted a systematic review of the epidemiologic evidence of the health effects of incinerators, classifying plants in three generations, according to emission limits. A systematic search identified 63 epidemiologic studies, published in English, investigating health effects of incinerators on humans. We focused on cancer, cardio-cerebrovascular diseases (CVD) and respiratory diseases, pregnancy outcomes and congenital anomalies. Only six studies in the general population were on third generation incinerators providing data on pregnancy outcomes and congenital anomalies. Given the heterogeneity of methods, the abundance of ecological/semi-ecological studies and the lack of reliable quantitative measures of exposure in several studies we did not perform any meta-analysis. No excesses emerged concerning all cancers and lung cancer. An excess of non-Hodgkin lymphoma was reported in some earlier studies, but not for second generation plants. Possible excesses of soft tissue sarcomas were confined to earlier incinerators and the areas closer to the plants. No clear association emerged for CVD and diseases of the respiratory system. Several different pregnancy outcomes were considered, and no consistent association emerged, in spite of a few positive results. Studies were negative for congenital anomalies as a whole. Sporadic excesses were reported in a few studies for specific types of anomalies, but no consistent pattern emerged. Evaluation of the evidence was hindered by heterogeneity in reporting and classification of outcomes across studies. Direct evidence from third generation plants is scarce. Methodological issues in study design (mainly related to exposure assessment, confounding and ecological design) and analysis make interpretation of results complex. In spite of this, the overall evidence suggests that, if there were any excesses at all for older incinerators, they were modest at most. Additional monitoring of third generation plants needs to overcome methodological weaknesses.

The use of in vitro testing to refine cumulative assessment groups of pesticides: The example of teratogenic conazoles.

The most relevant issues in cumulative risk assessment (CRA) are the identification of cumulative assessment groups and the hypothesis of dose-additivity, at relevant human exposures. In vitro methods can provide meaningful data to help solving those issues. Integration of in vitro studies, selected in vivo studies, and PBPK modeling for teratogenic conazoles confirmed that in vitro studies may give results in a cheaper and faster fashion. In particular, in vitro studies with explanted rat embryos provided support for dose-additivity for conazoles causing cranio-facial malformations. Although this could not be immediately quantitatively transferred to the in vivo situation, they provided indication on how to conduct targeted in vivo studies. In addition, by means of PBPK modeling, it was possible to estimate the dose in humans associated with a defined teratogenic risk and also to conclude that for cumulative risk assessment only exposures occurring within a short period of time (a day or less) need to be cumulated. Although PBPK modeling cannot be widely applied, at least in the short term, it should be considered if available. It is recommended to incorporate in vitro testing and PBPK modeling, whenever available and feasible in the process of risk assessment, particularly of CRA.

Risk assessment and management of occupational exposure to pesticides in agriculture.

Nearly 50% of the world labour force is employed in agriculture. Over the last 50 years, agriculture has deeply changed with a massive utilisation of pesticides and fertilisers to enhance crop protection and production, food quality and food preservation. Pesticides are also increasingly employed for public health purposes and for domestic use. Pesticide are unique chemicals as they are intrinsically toxic for several biological targets, are deliberately spread into the environment, and their toxicity has a limited species selectivity. Pesticide toxicity depends on the compound family and is generally greater for the older compounds; in humans, they are responsible for acute poisonings as well as for long term health effects, including cancer and adverse effects on reproduction. Due to their intrinsic toxicity, in most countries a specific and complex legislation prescribes a thorough risk assessment process for pesticides prior to their entrance to the market (pre-marketing risk assessment). The post-marketing risk assessment takes place during the use of pesticides and aims at assessing the risk for exposed operators. The results of the risk assessment are the base for the health surveillance of exposed workers. Occupational exposure to pesticides in agriculture concerns product distributors, mixers and loaders, applicators, bystanders, and rural workers re-entering the fields shortly after treatment. Assessing and managing the occupational health risks posed by the use of pesticides in agriculture is a complex but essential task for occupational health specialists and toxicologists. In spite of the economic and social importance of agriculture, the health protection of agricultural workforce has been overlooked for too many years, causing an heavy tribute paid in terms of avoidable diseases, human sufferance, and economic losses. Particularly in the developing countries, where agricultural work is one of the predominant job, a sustainable model of development calls for more attention to occupational risks in agriculture. The experience of many countries has shown that prevention of health risk caused by pesticides is technically feasible and economically rewarding for the individuals and the whole community. A proper risk assessment and management of pesticide use is an essential component of this preventative