Toxicological data analysis to support grouping of pesticide active substances for cumulative risk assessment of effects on liver, on the nervous system and on reproduction and development

Wolterink, Gerrit; Kesteren, Petra van; Mahieu, Karin; Ven, Bianca van de; Ossendorp, Bernadette C.; Ruggeri, Lucia; Tosti, Luca; Metruccio, Francesca; Schlitt, Christian; Moretto, Angelo; Printemps, Nathalie; Gouze, M.-E.; Charles, Sandrine; Angeli, Karine; Fastier, A.; Mercier, Thierry Le

doi:10.2903/sp.efsa.2013.en-392

Cited by 10 publications

(11 citation statements)

References 34 publications

(28 reference statements)

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“…The assessment of mixtures of chemicals is very complex for toxicologists and regulators (Monosson, ; Kienzler et al, ) and is currently a major challenge in many countries worldwide (Feron et al, ; Simmons, ). Even though significant progress has been made in investigating the toxicity of mixtures in the last 15 years (Crépet et al, ; EFSA, ; Wolterink et al, ), the new methodologies still have several limitations. Notably, there is no consistent terminology to describe various aspects of exposure and the effect of mixtures.…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet

Kopp

Vignard

Mirey

et al. 2018

Environ and Mol Mutagen

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Through diet, people are exposed simultaneously to a variety of contaminants (e.g. heavy metals, mycotoxins, pesticides) that could have combined adverse effects on human health. A previous study identified six main mixtures of food contaminants to which French adult consumers are exposed. These complex mixtures are comprised of 11 to 19 chemicals that have numerous toxic properties. In the present study, we investigated the genotoxic effects of these food contaminants, as single molecules and in mixtures that reflect their occurrence in the French diet, using the γH2AX assay in two human cell lines (HepG2, LS-174 T). Results of detailed analysis of the 49 individual contaminants (including 21 tested in this study) demonstrated a positive genotoxic response to 14 contaminants in HepG2 and 12 in LS-174 T cells. Next, our results indicated that two mixtures out of six triggered significant γH2AX induction after 24 hr of treatment, at concentrations for which individual compounds did not induce any DNA damage, suggesting more than additive interactions between chemicals. γH2AX positive mixtures were then tested for mutagenicity with the innovative in vitro PIG-A assay in HepG2 cells coupled with the soft agar colony formation assay. The two γH2AX positive mixtures led to a significant increase in the frequency of PIG-A GPI-deficient cells and in the number of colonies formed in soft agar. In conclusion, our study demonstrates that two mixtures of contaminants present in the French diet induce genotoxicity and mutagenicity, and that the combined effects of single molecules present in these mixtures are likely not additive, highlighting potential problems for hazard assessment of mixtures. Environ. Mol. Mutagen. 59:742-754, 2018. © 2018 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet

Kopp

Vignard

Mirey

et al. 2018

Environ and Mol Mutagen

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“…Brain and/or erythrocyte AChE inhibition was considered adverse when it reached a statistically significant (p < 0.05) decrease of 20% or more compared to concurrent control groups. Data collection spreadsheets elaborated by EFSA's contractors (RIVM, ICPS, ANSES, 2013, 2016 were used to the purpose of the toxicological characterisation. Only studies assessed as 'acceptable' in the final DAR or RAR were considered.…”

Section: Cumulative Assessment Groups (Cags)mentioning

confidence: 99%

“…This transfer of information was performed by EFSA contractors. The methodology to collect 30 EFSA, 2006 and report the information is precisely described in 2 external scientific reports (RIVM, ICPS, ANSES, 2013, 2016.…”

Section: Ethephon (Op)mentioning

confidence: 99%

Cumulative dietary risk assessment of chronic acetylcholinesterase inhibition by residues of pesticides

Anastassiadou¹,

Choi²,

Čoja³

et al. 2021

EFS2

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A retrospective cumulative risk assessment of dietary exposure to pesticide residues was conducted for chronic inhibition of acetylcholinesterase. The pesticides considered in this assessment were identified and characterised in a previous scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2016, 2017 and 2018, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained by means of a two-dimensional probabilistic model, which was implemented in SAS ® software. The characterisation of cumulative risk was supported by an uncertainty analysis based on expert knowledge elicitation. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides contributing to the chronic inhibition of acetylcholinesterase does not exceed the threshold for regulatory consideration established by risk managers.

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“…A second project was outsourced to re-evaluate the data and, to specifically identify pesticides having effects on the nervous system, the liver and the reproductive and developmental system. In addition, pesticides approved from 31 May 2009 until 1 January 2012 were included in the scope of the second project (Wolterink et al, 2013).…”

Section: Identification Of Cumulative Assessment Groups Of Pesticidesmentioning

confidence: 99%

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

2013

EFS2

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The development of harmonised terminology and frameworks for the human risk assessment of combined exposure to multiple chemicals ("chemical mixtures") is an important area for EFSA and a number of activities have already been undertaken, i.e. in the fields of pesticides and contaminants. The first step prior to a risk assessment of combined exposure to multiple chemicals is problem formulation defining the relevant exposure, hazard and population to be considered. In practice, risk assessment of multiple chemicals is conducted using a tiered approach for exposure assessment, hazard assessment and risk characterisation. Higher tiers require increasing knowledge about the group of chemicals under assessment and the tiers can range from tier 0 (default values, data poor situation) to tier 3 (full probabilistic models). This scientific report reviews the terminology, methodologies and frameworks developed by national and international agencies for the human risk assessment of combined exposure to multiple chemicals and provides recommendations for future activities at EFSA in this area. SUMMARYHuman risk assessment of combined exposure to multiple chemicals (chemical mixtures) poses several challenges to scientists, risk assessors and risk managers, particularly the complexity of the terminology and problem formulation, the diversity of chemical entities, and the toxicological profiles and exposure patterns in test species and humans. This scientific report aims to describe the terminology and methodologies, review frameworks developed by national and international agencies and discuss future activities at EFSA in this area.

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Toxicological data analysis to support grouping of pesticide active substances for cumulative risk assessment of effects on liver, on the nervous system and on reproduction and development

Abstract: Suggested citation: Vv.Aa.; Toxicological data analysis to support grouping of pesticide active substances for cumulative risk assessment of effects on liver, on the nervous system and on reproduction and development. Supporting Publications

Cited by 10 publications

References 34 publications

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet

Cumulative dietary risk assessment of chronic acetylcholinesterase inhibition by residues of pesticides

International Frameworks Dealing with Human Risk Assessment of Combined Exposure to Multiple Chemicals

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