Compounded conservatism in European re-entry worker risk assessment of pesticides

Kluxen, Felix M.; Felkers, Edgars; Baumann, Jenny; Morgan, Neil; Wiemann, Christiane; Stauber, Franz; Strupp, Christian; Adham, Sarah; Küster, Christian

doi:10.1016/j.yrtph.2021.104864

Cited by 19 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, lower doses are associated with a higher absolute amount absorbed, since stratum corneum residue was not removed by washing or due to a high skin association. It was previously argued that residue in the stratum corneum does not contribute to systemic dose (Aggarwal et al 2014 , 2015 ) and is not relevant for 24-h risk assessment (Kluxen et al 2021 ). The log–log plot shows how the absorption relationship is skewed for some active ingredients when generically including stratum corneum .…”

Section: Resultsmentioning

confidence: 99%

“…The current approach for non-dietary risk assessment binds resources because the assessment is complicated and time consuming. It also results in very conservative absorption estimates, as it compounds conservatism already built into the assay design (Kluxen et al 2021 ), which then often triggers further studies that also need to be incorporated in exposure assessments and risk evaluations.…”

Section: Discussionmentioning

confidence: 99%

“…However, as described above, in a functional biological system, the systemic concentration of a test item is dynamic as a function of at least penetration and excretion. Hence, the effect on small doses should be covered by the conservative nature of the assay system (Kluxen et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…One key issue in dermal penetration studies is that other ADME processes are not considered. First, because only cumulative penetration is assessed and further only the recovery of the (typically) radiolabeled compound equivalent is assessed independently of whether the amount penetrated corresponds to the original radiolabelled compound or degradates/metabolites thereof (Kluxen et al 2021 ). The in vitro studies ignore any excretion kinetic which is in counterbalance to the penetration.…”

Section: Methodsmentioning

confidence: 99%

“…EFSA applies much scrutiny to the in vitro dermal absorption assay evaluation, see EFSA dermal absorption guidance (EFSA 2017 ), to avoid hypothetical under-prediction of absorption. EFSA’s dermal absorption estimate derivation rules have been reviewed elsewhere (Kluxen et al 2021 ) and in practice only increase study-derived values without intending to derive realistic absorption estimates. True dermal absorption under-prediction is very unlikely based on the assay design and conduct itself because it only considers cumulative dermal penetration and no other toxicologically relevant absorption, distribution, metabolism and excretion (ADME)/kinetic or dynamic processes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Kluxen¹,

Felkers²,

McEuen

et al. 2022

Arch Toxicol

Self Cite

View full text Add to dashboard Cite

Dermal absorption values are used to translate external dermal exposure into potential systemic exposure for non-dietary risk assessment of pesticides. While the Environmental Protection Agency of the United States of America (US EPA) derives a common dermal absorption factor for active substances covering all related products, the European Food Safety Authority (EFSA) requests specific product-based estimates for individual concentrations covering the intended use rates. The latter poses challenges, because it disconnects exposure dose from applied dose in absorption studies, which may not be suitable in scenarios where concentration is not relevant. We analyzed the EFSA dermal absorption database, collected 33 human in vitro studies from CropLife Europe (CLE) companies, where ≥3 in-use dilution concentrations were tested, and 15 dermal absorption triple pack datasets. This shows that absolute dermal absorption correlates with absolute applied dose on a decadic logarithm-scale, which is concordant with the toxicological axiom that risk is driven by exposure dose. This method is radically different from the current European approach focused on concentrations and offers new insights into the relationship of internal and external exposure doses when utilizing data from in vitro studies. A single average dermal absorption value can be simply derived from studies with multiple tested concentrations, by calculating the y-intercept of a linear model on a decadic logarithm scale while assuming a slope of 1. This simplifies risk assessment and frees resources to explore exposure refinements. It also serves as a basis to harmonize dermal absorption estimation globally for use in exposure-driven risk assessments.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Kluxen¹,

Felkers²,

McEuen

et al. 2022

Arch Toxicol

Self Cite

View full text Add to dashboard Cite

show abstract

Protection by ordinary light clothing against pesticide spray drift for bystanders and residents

Felkers

Küster

Adham³

et al. 2023

J Consum Prot Food Saf

Self Cite

View full text Add to dashboard Cite

There are stringent EU regulatory requirements to assess pesticide exposure to bystanders and residents to direct spray drift. A “light clothing” adjustment factor (AF) of 0.82 is applied in the exposure assessment, based on simple assumptions for covered body surface and penetration through clothing. To assess the appropriateness of the AF, we collated data from 32 field studies. The mean and 25th percentile % reduction from ordinary light clothing (“reduction %”) in children and adults for all crops and standard and drift-reducing nozzles were 42.7% and 36.2%, resulting in AF of 0.573 and 0.638, respectively. Sources of variation were investigated, e.g. crop type, leaf coverage, buffer, spray pressure, and nozzle type, which indicated that reduction % could be impacted by several conditions. The reduction % is similar between crops; therefore, a single AF value covering all crops can be derived. One exception was for early-stage vineyard scenarios (the reduction % is lower (27%) than late stage (42–47%)) and could be considered individually to avoid unnecessary conservatism for the other scenarios. This evaluation demonstrates the current AF to be overly precautionary, and a more realistic, exposure scenario-relevant value could be applied for bystander/resident risk assessments.

show abstract

In silico prediction of dermal absorption from non-dietary exposure to plant protection products

Küster

Baumann²,

Braun³

et al. 2022

Computational Toxicology

View full text Add to dashboard Cite

Compounded conservatism in European re-entry worker risk assessment of pesticides

Cited by 19 publications

References 40 publications

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Protection by ordinary light clothing against pesticide spray drift for bystanders and residents

In silico prediction of dermal absorption from non-dietary exposure to plant protection products

Contact Info

Product

Resources

About