A Tiered Approach for Assessing Individual and Combined Risk of Pyrethroids Using Human Biomonitoring Data

Abstract

Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014–2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1–0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future.

Child exposure to organophosphate and pyrethroid insecticides measured in urine, wristbands, and household dust and its implications for child health in South Africa: A panel study

“…This is aligned with what has been reported in Europe, where human biomonitoring data revealed low health concerns related to PYR exposure. 91 Nevertheless, it should be noted that in this study, the calculated exposure is likely to be poorly estimated as specific PYR biomarkers (e.g., cis -DBCA, 91 the specific biomarker for deltamethrin) were not available for use. Therefore, further studies tackling this limitation will allow us to understand better the health risks of single and cumulative exposure to PYRs for our population.…”

Applicability of Food Monitoring Data for Assessing Relative Exposure Contributions of Pyrethroids in Retrospective Human Biomonitoring Risk Estimations

“…This assessment is based on aggregated human biomonitoring data (as percentiles for each country and age group) from HBM4EU-aligned studies described in a previous publication [ 9 ]. Concentrations of pyrethroid metabolites 3-PBA, F-3-PBA, Σ(cis-DCCA + trans-DCCA) (3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropanoic acid), cis-DBCA (cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid), and CIF3CA (chlorotrifluorovinylcyclo-propane carboxylic acid (or cis-3-[2-chloro-3,3,3-trifluoroprop-1-enyl]-2,2-dimethylcyclopropanecarboxylic acid)), expressed as ug/l urine were selected.…”

“…The expected levels of urinary pyrethroid metabolites for each diet were estimated as described previously [ 16 ] using the molar urinary fractions for pyrethroids proposed by Tarazona et al [ 9 ]. Briefly, the urinary levels expected for each metabolite at any daily dietary exposure of the parent pesticide can be estimated according to the following equation: where Fue is the molar urinary fraction of the metabolite, and MWratio is the ratio between the molecular weights of the metabolite and the parent pesticide.…”

“…The calculated values were then compared with the respective HBM-GV Gen Pop for adults and children to estimate the hazard quotients (HQs) associated with the measured values for each pyrethroid and for the combined exposure to all pyrethroids contributing to the urinary metabolite levels. The HBM-GV Gen Pop proposed in the previous assessment [ 9 ] was updated according to the new ADI values proposed by EFSA if needed (see also Table S1 and File S1 in the Supplementary Material for details). The total risk for the aggregate exposure was estimated by summing up the HQs obtained for each active substance.…”

“…However, even the more specific metabolites, corresponding to the acid moiety, are frequently shared by two or more active substances, each with different toxicity potency, adding complexity to the interpretation of biomonitoring results as health indicators. In a previous work [ 9 ], a tiered retrospective risk assessment approach for assessing pyrethroid urinary metabolites was proposed. Potential concerns, particularly for children, were identified at the screening level.…”