Toxicological Reference Values Research Articles

Setting of residue definitions and toxicological reference values for ethiprole.

In accordance with Article 6 of Regulation (EC) No 396/2005, the original evaluating Member State (EMS), the United Kingdom, received an application from Bayer CropScience to set an import tolerance for the non-approved active substance ethiprole in rice. In the framework of the assessment process, the application was re-allocated to the Netherlands and the purpose of the application was changed to only set European residue definitions and toxicological reference values for the active substance ethiprole. Based on the assessment of the available toxicological data, an acceptable daily intake of 0.002 mg/kg bw per day and an acute reference dose of 0.005 mg/kg bw were derived. The data submitted in support of the request were found to be sufficient to derive residue definitions in primary crops and in processed commodities. The residue definition for enforcement was derived as 'ethiprole'. Adequate analytical methods for enforcement are available to control the residues of ethiprole in dry commodities at the validated LOQ of 0.002 mg/kg. A residue definition for risk assessment was derived as the 'sum of ethiprole, ethiprole-sulfone (RPA097973) and ethiprole-amide (RPA112916), expressed as ethiprole'. This residue definition is applicable for foliar treatment in all primary crops, for both foliar and soil treatments in cereals crops, and is also valid for processed commodities.

Targeted review of the maximum residue levels (MRLs) for dimethomorph.

In accordance with Article 43 of Regulation (EC) No 396/2005, the European Commission requested EFSA to perform a targeted risk assessment for dimethomorph considering the residue definition and the toxicological reference values (TRVs) derived during the renewal of the approval of dimethomorph and the most recent version of the EFSA Pesticide Residues Intake Model (PRIMo) (rev.3.1). EFSA confirmed that the current TRVs are sufficiently protective for consumers, including the identified hazard indicative of endocrine disruption. Furthermore, EFSA identified all the codex maximum residue limits (CXLs) and import tolerances that are covered by existing maximum residue levels (MRLs) and performed chronic and acute dietary risk assessment to support risk managers during the decision-making. A screening of all existing MRLs was also performed. The exposure calculations performed by EFSA showed that the existing MRLs, including the ones based on CXLs or import tolerances, do not lead to consumers intake concerns.

Arsenic content in tissues, Fungus combs, Herbs, Termite mounds and Soils of termites of the genus Macrotermes and assessment of the health risk associated with their food use in the industrial zone of the Societe Nouvelle Des phosphates du Togo (SNPT)

Arsenic is present in different environmental matrices of the phosphate mining and processing area of the Société Nouvelle des Phosphates du Togo; including termite tissues, termite waste, termite mounds, termite Fungus combs, soils and nearby herbs. Arsenic levels vary across matrices, with termite waste having the highest concentration (approximately 27.01 mg/kg) compared to the outside herbs, which have the lowest. Phosphate mining sites, including Hahotoé-Kpogamé and Akoumapé, have higher levels of As contamination in soils and termite tissues compared to the phosphate processing site. A positive correlation is observed between As levels in termite tissues and termite waste; suggesting an ability of termites to eliminate arsenic via their waste. Regarding health risks, the hazard quotient (HQ) for arsenic in termites exceeds 1, and for non-threshold effects, the excess individual risk (EIR) assessment gives EIR > 10-4 in both adults and children; which would mean that termite consumption poses a significant health risk, including cancer risks for human populations, particularly children. However, it should be noted that the estimation in this study includes total As (organic and inorganic). Since the toxicological reference values were calculated on the basis of inorganic arsenic, which presents more hazard and whose fraction represents 10% of total As, the daily exposure dose values for adults and children represent 1.40.10-4 mg/kg/d and 1.02.10-4 mg/kg/d of inorganic arsenic, respectively. These doses will then become lower than the toxicological reference value (TRV) with the consequence of hazard quotient (HQ) lower than 1 and resulting in low risks of carcinogenic effects. It is therefore necessary to specifically determine the inorganic fraction to refine the risk assessment and to extend this study to other trace elements in the prospected area.

Roe deer exposure to trace metals and pesticides in forests and agricultural plains of North-eastern France.

Human activities related to agriculture and industrial development result in the emission of different types of pollutants in the environment. The phytosanitary pressure depends on the time of the year, the type of habitat, and the used treatments. Wildlife, particularly ungulates, can be exposed to pesticides and trace metals through their herbivorous diet directly impregnated by the environmental contamination. Wild game thus plays a sentinel role but can also represent a risk for human health by exposing venison consumers to these contaminants. The present study explored this dual problem in two types of habitat: forests and agricultural plains located in North-eastern France. Samples of liver and muscle were taken from ten roe deer, five caught on the forests and five others in the plains, to determine contaminant levels. There was no significant difference in contamination of roe deer livers according to the habitat for three trace metals (chromium, nickel, and copper), while lead concentrations were higher in samples from the plain (0.85 vs. 0.74mg·kg-1 dry matter DM; P < 0.01). Conversely, zinc concentrations were higher in forest roe deer (110 vs. 95mg·kg-1 DM; P < 0.05). Cadmium concentrations did not differ significantly between the two habitats, but forest samples showed strong inter-individual variability, with some values close to those observed on the plains and others higher (1.8 vs. 0.3mg·kg-1 DM for forest and plain, respectively; P = 0.11). Mercury was not detected in any sample. The majority of pesticides investigated were not detected. Only a few pesticides were in trace amount (from 1 to 8µg·kg-1 fresh matter), either in the liver (e.g., heptachlor and oxychlordane) or in both tissues, liver and muscle (e.g., pyridalyl). Some compounds were only detected in plain (e.g., cypermethrin and fenpropidin) and others in forest (piperonyl butoxide and pyridalyl) samples. Analyses mainly detected insecticides in samples taken from forests and agricultural plains. Fungicides and a few herbicides were mainly detected in plain sampled animals. Pesticides and copper concentrations in roe deer tissues were lower than maximum residue levels established for farm (copper) or wild terrestrial (pesticides) animals. Cadmium concentrations were also lower than the maximum level for most samples, except for some forest roe deer. However, both forest and plain roe deer exceeded the maximum level for lead in liver. Human exposure was simulated according to different amounts of meat consumed and compared with toxicological reference values. This study highlighted an overall low risk to human health for both pesticides, copper and lead, with more reservations about cadmium for some roe deer shot in forest. The differences in roe deer contamination between forests and agricultural plains for some trace elements and organic pollutants confirmed the sentinel role of this species.

Identification and health risk assessment of volatile and semi-volatile migrants along with chemical elements in food contact water-borne coating paper

Water-borne coating paper, with its food contact potential, raises concerns due to unknown contaminants. Herein, the presence and migration of volatile and semi-volatile compounds, along with chemical elements from two water-borne coating paperboards were investigated using 4 % acetic acid, 50 % ethanol, and 95 % ethanol, while also evaluating associated health risks. The results showed that the overall migration to 95 % ethanol from both papers indicated the non-compliance with the reference limit of 10 mg/dm2. Utilizing an optimized direct immersion-solid-phase microextraction coupled to gas chromatography-mass spectrometry method, a total of 66 migrants were identified, among which 16 and 7 were classified as Cramer Ⅲ and Cramer Ⅱ, respectively, linked to coating and paper raw materials. Additionally, 28 chemical elements released from papers were analysed using inductively coupled plasma mass spectrometry, where higher levels of elements (i.e., Na, K) were observed in the migration of 4 % acetic acid, potentially from additives or raw materials used in papermaking processes. More importantly, health risk assessment based on the Threshold of Toxicological Concern approach or worst-case dietary intake assumption indicated that, the estimated daily intake of most migrants and chemical elements through human exposure fell below toxicological reference values. However, certain migrants (e.g., 2-ethylhexyl acrylate, methyl benzoate, phenanthrene, and longifolene) exhibited concerning migration levels in 50 % ethanol and 95 % ethanol that exceed their safety thresholds and may pose health risks. Overall, understanding the migration and potential risk of migrants are imperative for ensuring the safety of using commercially available water-borne coating paper in food contact applications.

Heavy metals (Pb, Cd, Ni) in insect-based products for human consumption sold by e-commerce in the EU market: Occurrence and potential health risk associated with dietary exposure

Ensuring the safety of insect-based products (IBPs) is essential considering their potential as food source in the future. Among food contaminants, heavy metals represent a concern for food safety. In this study, the concentrations of lead (Pb), cadmium (Cd), and nickel (Ni) in 52 IBPs marketed on European e-commerce were assessed. The analyses were conducted with Graphite Furnace Atomic Absorption Spectrometry. The impact of consuming IBPs on the toxicological reference values for each analyzed heavy metal was also assessed, to characterize the potential human health risks. Results showed a statistically significant higher concentration of Pb in products containing a percentage greater than 50% of insects compared to those with lower percentage of inclusion. Specifically, 70% of samples containing 100% insect powder exceeded the Pb levels established by regulation, while 10% exceeded the Cd limits. The Ni values, higher respect to other studies, were compared with the mean values reported by the EFSA monitoring plan on foodstuff, showing that our data mainly fell between grain and other vegetables products, which have a greater nickel content respect to products of animal origin. According to EFSA, the health risk assessment conducted suggests that consuming products containing A. diaperinus, A. domesticus, L. migratoria, and T. molitor as proposed does not significantly contribute to overall dietary exposure to heavy metals. However, 4.24% of the Margins of Exposure for Pb were above 1 but below 10, suggesting a very low health risk, while 12.30% of the Margins of Exposure for Ni were lower than 30, indicating potential health risks for sensitized individuals. The importance of rigorous monitoring of heavy metal contamination to ensure the safety of IBPs and the need for continued research to mitigate potential health risks associated with their consumption were highlighted.

Ambient air concentrations of plant protection products: Data collection for the combined air concentration database and associated risk assessment

CropLife Europe collected literature values from monitoring studies measuring air concentrations of Plant Protection Products (PPPs) that may be inhaled by humans located in rural areas but not immediately adjacent to PPP applications. The resulting “Combined Air Concentration Database” (CACD) was used to determine whether air concentrations of PPPs reported by the French “Agency for Food, Environmental and Occupational Health & Safety” (ANSES) are consistent with those measured by others to increase confidence in values of exposure to humans. The results were put into risk assessment context. Results show that 25–90% of samples do not contain measurable PPP concentrations. Measured respirable fractions were below EU default air concentrations used for risk assessment for resident exposure by the European Food Safety Authority. All measured exposures in the CACD were also below established toxicological endpoints, even when considering the highest maximum average reported concentrations and very conservative inhalation rates. The highest recorded air concentration was for prosulfocarb (0.696 μg/m³ measured over 48 h) which is below the EFSA default limit of 1 μg/m³ for low volatility substances. In conclusion, based on the CACD, measured air concentrations of PPPs are significantly lower than EFSA default limits and relevant toxicological reference values.

Biocide and other semi-volatile organic compound concentrations in settled indoor dust of CRESPI daycare centers and implication for public health

This study investigates the presence of biocides and other semi-volatile organic compounds (SVOCs) in cleaning products used in daycare centers and health impact through ingestion of settled dust by young children. In Paris metropolitan area, 106 daycares area were investigated between 2019–2022. Fifteen substances were analyzed in settled indoor dust by gas chromatography-tandem mass spectrometry. Detection rates and concentrations ranged from 5 to 100%, and <LOD to 14,267 ng/g, respectively. Galaxolide and benzophenone showed highest median concentration respectively 884 ng/g and 819 ng/g. The daily intakes (DI) of the substances through settled dust ingestion were evaluated and compared to those from food, inhalation, and dermal contact reported in the literature. Daily intakes from settled dust for musks, triclosan, geraniol, benzophenone, 2-phenylphenol, bifenthrin, and 4-n-nonylphenol were lower than those reported in the literature. The proportion of dust ingestion to total DI was negligible, except for benzophenone (DI=34%) for children aged 3 to 11 months. The DIs were well below the respective toxicological reference values for isothiazolinones, 4-tert-butylphenol, chlorocresol, and diclosan. Our results suggest that exposure to these biocides and the other SVOCs, taken individually, by dust ingestion in daycares, is not a major public health concern. Benzophenone, presumed carcinogen for humans, may require further investigation because of its presence in several daycares.

Biomonitoring Equivalents for ethylene thiourea

Ethylene thiourea, or ETU, is used in the rubber industry and is a degradation product and impurity in some fungicides. The general public may be exposed to low concentrations of residues of ETU in a variety of ways, including food treated with ethylene bis-dithiocarbamate (EBDC) fungicides or migration from rubber products. Biomonitoring of ETU in urine is useful for an assessment of integrated exposures to ETU across different sources and routes of exposure. In this evaluation, we review available health-based risk assessments and toxicological reference values (TRVs) for ETU and derive Biomonitoring Equivalent (BE) values for interpretation of population biomonitoring data. BEs were derived based on existing TRVs derived by Health Canada, yielding a BE of 27 μg of total ETU/L in urine associated with the Acceptable Daily Intake (ADI) and 6.7 μg/L associated with a 1e-6 cancer risk. These BEs are based on an analytical method that involves a digestion step to liberate conjugated ETU, thus producing ‘total’ ETU in urine. The BE values derived in this manuscript can serve as a guide to help public health officials and regulators interpret population based ETU biomonitoring data in a public health risk context.

PBPK modeling to support risk assessment of pyrethroid exposure in French pregnant women

BackgroundPyrethroids are widely used pesticides and are suspected to affect children's neurodevelopment. The characterization of pyrethroid exposure during critical windows of development, such as fetal development and prenatal life, is essential to ensure a better understanding of pyrethroids potential effects within the concept of Developmental Origins of Health and Disease. ObjectiveThe aim of this study was to estimate maternal exposure of French pregnant women from biomonitoring data and simulate maternal and fetal internal concentrations of 3 pyrethroids (permethrin, cypermethrin and deltamethrin) using a multi-substance pregnancy-PBPK (physiologically based pharmacokinetics) model. The estimated maternal exposures were compared to newly proposed toxicological reference values (TRV) children specific also called draft child-specific reference value to assess pyrethroid exposure risk during pregnancy i.e. during the in utero exposure period. MethodsA pregnancy-PBPK model was developed based on an existing adult pyrethroids model. The maternal exposure to each parent compound of pregnant women of the Elfe (French Longitudinal Study since Childhood) cohort was estimated by reverse dosimetry based on urinary biomonitoring data. To identify permethrin and cypermethrin contribution to their common urinary biomarkers of exposure, an exposure ratio based on biomarkers in hair was tested. Finally, exposure estimates were compared to current and draft child-specific reference values derived from rodent prenatal and postnatal exposure studies. ResultsThe main contributor to maternal pyrethroid diet intake is cis-permethrin. In blood, total internal concentrations main contributor is deltamethrin. In brain, the major contributors to internal pyrethroid exposure are deltamethrin for fetuses and cis-permethrin for mothers. Risk is identified only for permethrin when referring to the draft child-specific reference value. 2.5% of the population exceeded permethrin draft child-specific reference value. ConclusionsA new reverse dosimetry approach using PBPK model combined with human biomonitoring data in urine and hair was proposed to estimate Elfe pregnant population exposure to a pyrethroids mixture with common metabolites.

A Survey of the Levels of Selected Metals in U.S. Meat, Poultry, and Siluriformes Fish Samples Taken at Slaughter and Retail, 2017–2022

The U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) conducts surveillance of metallic elements in U.S. meat, poultry, and Siluriformes fish samples collected immediately postmortem as part of its National Residue Program (NRP). From 2017 to 2022, 13,966 samples were analyzed under the NRP. The Federal Emergency Response Network (FERN) Cooperative Agreement Program (CAP) tests meat, poultry, and Siluriformes fish products collected at retail in the United States for metals. From 2018 to 2022, 2,902 samples were analyzed by FERN CAP laboratories. Meat and poultry samples collected by FSIS show that most metals were not detected at all or were detected infrequently. Meat is a rich source of iron and zinc, and iron was detected in 22% (1,255/5,623) and zinc was detected in 48% (2,742/5,676) of meat and poultry samples, respectively. The percentage of samples testing positive for manganese, molybdenum, lead, and cadmium were higher in the FERN CAP retail samples than in FSIS samples. Expected human exposure from average levels of lead and cadmium found in meat and poultry was compared to toxicological reference values and was not found to exceed these values. Detections of arsenic and mercury were found more often in Siluriformes fish samples (2017–2022) than in terrestrial animals. Trace amounts of arsenic and mercury were detected in 8% and 4% of Siluriformes samples, respectively, but were not detected at levels that raise concern. On the whole, both the FSIS and FERN CAP datasets provide reassuring evidence of the safety of the FSIS-regulated food supply with regard to the studied elements.

Distribution of Pesticides and Polychlorinated Biphenyls in Food of Animal Origin in Croatia.

Pesticides and polychlorinated biphenyls (PCBs) are persistent environmental pollutants. When entering the food chain, they can represent a public health problem due to their negative effects on health. In this study, concentrations of organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), pyrethroids, carbamates, and PCBs-a total 73 compounds-were determined in a total of 2268 samples of fat tissues (beef, pork, sheep, goat, poultry, game, horse, rabbit) and processed fat, meat, and processed meat products collected in Croatia during an 8-year period. In fatty tissues, 787 results exceeded the limits of quantification (LOQ): 16 OCPs, eight OPPs, six pyrethroids, one carbamate, and seven PCBs. The most positive results in fat samples were found for OCPs, with a frequency of quantification in the range of 57.5-87.5%. Hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (DDE) were quantified in the highest percentages, in the ranges of 5.5-66.7% and 5.4-55.8%. Concentrations above the MRL values were determined for chlorpyrifos in pork fat and for resmethrin in six fat samples and one pâté. In 984 samples of meat and meat products, only 62 results exceeded the LOQ values. The highest frequency of quantification was determined for OCPs (25 samples), of which 40% were DDT isomers (60% DDE). Frequency quantifications of PCBs in fat samples were between 7.23 and 36.7%. An evaluation of the health risk assessment showed that the consumption of fat, meat, and meat products does not pose a threat to consumer health, since all EDI values were well below the respective toxicological reference values.

Statement on the refined environmental risk assessment and impact of the new classification for captan.

On 24 July 2020, the EFSA conclusion on the peer review of the pesticide risk assessment of the active substance captan drawn in the context of the renewal of approval of the active substance captan conducted in accordance with Commission Implementing Regulation (EC) No 844/2012 was approved. In December 2023, the European Commission asked EFSA to provide a statement on its view as regards the RMS's revised environmental risk assessment concerning some uses in pome fruits and cherries and the potential impact of the recent new classification recommended by RAC on the toxicological reference values of captan stated in the EFSA Conclusion. The current statement contains the conclusions of the considerations related to the environmental revised risk assessment performed by the RMS, Austria, and to the new classification proposed by RAC on the toxicological reference values.

Updated reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate-methyl.

In compliance with Article 43 of Regulation (EC) No 396/2005, EFSA received from the European Commission in 2020 a mandate to provide its reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate-methyl. Specifically, EFSA was asked to assess whether thiophanate-methyl or carbendazim has clastogenic potential and, in case clastogenic potential can be excluded, to derive toxicological reference values necessary for consumer risk assessment and assessment of maximum residue levels (MRLs). Although these active substances are no longer authorised within the European Union, MRLs were established by the Codex Alimentarius Commission (codex maximum residue limits; CXLs), and import tolerances are in place. Based on the assessment of the available data, toxicological reference values and MRL proposals were derived and a consumer risk assessment was carried out. Some information required by the regulatory framework was found to be missing and a possible acute risk to consumers was identified. Hence, the consumer risk assessment was considered indicative only and all MRL proposals derived by EFSA still require further consideration by risk managers. In October 2022, to ensure that MRLs derived by EFSA in its assessment of 2021 are safe for consumers also in view of endocrine-disrupting properties, EFSA was requested to carry out a follow-up assessment taking into account the scientific criteria for identifying endocrine disruptors (ED). Based on the outcome of the assessment, the experts agreed that the reference values are also covering the concern related to the identified hazards indicative of endocrine disruption for thiophanate-methyl. No further considerations on the impact of the ED assessment on the current reference values were needed for carbendazim since the ED criteria are not met for this substance. Therefore, the risk assessment and the MRL recommendations derived in 2021 are confirmed.

Targeted review of maximum residue levels (MRLs) for chlorfenapyr.

In accordance with Article 43 of Regulation (EC) 396/2005, EFSA received a request from the European Commission to review the existing maximum residue levels (MRLs) for the non-approved active substance chlorfenapyr in view of the possible lowering of the MRL set for tea. This current EU MRL is based on an import tolerance established in 2007. EFSA reviewed the toxicological data assessed by other scientific bodies, proposing toxicological reference values to be used for an indicative risk assessment, noting that the values are affected by additional, non-standard uncertainties. According to the indicative chronic and acute dietary risk assessment the existing MRL for tea does not pose an unacceptable risk for consumers. Further risk management discussions are required to decide which of the risk management options proposed by EFSA should be implemented in the EU MRL legislation.

Targeted review of maximum residue levels (MRLs) for dicofol.

In accordance with Article 43 of Regulation (EC) 396/2005, EFSA received a request from the European Commission to review the existing maximum residue levels (MRLs) for the non-approved active substance dicofol in view of the possible lowering of the MRL. EFSA investigated the origin of the current EU MRLs. All existing EU MRLs reflect previously authorised uses in the EU or are based on obsolete Codex Maximum Residue Limits. Furthermore, in view of the limitations of the toxicological dataset and related uncertainties, the existing toxicological reference values derived at the EU level cannot be confirmed for dicofol. EFSA therefore proposed lowering all existing EU MRLs for dicofol to the limit of quantification.

Biomonitoring Equivalents for N,N-Diethyl-meta-toluamide (DEET)

N,N-Diethyl-meta-toluamide (DEET) is widely used as an effective mosquito and tick repellent. DEET is absorbed systemically after applications to skin. Once absorbed, DEET is rapidly metabolized with the predominant metabolite being m-dimethylaminocarbonyl benzoic acid (DBA). DEET and metabolites are predominantly excreted in urine after being absorbed systemically. Exposures to DEET are typically biomonitored via measures of DEET and DBA in urine. In this evaluation, we review available health-based risk assessments and toxicological reference values (TRVs) for DEET and derive Biomonitoring Equivalent (BE) values for interpretation of population biomonitoring data. BEs were derived based on existing TRVs derived by Health Canada, yielding 38 and 23 mg/L DBA in urine for adults and 57 and 34 mg/L DBA in urine in children for the acute oral and intermediate dermal TRVs, respectively. The BEs for unchanged DEET in urine are 21 and 12 mg/L in adults and 4.5 and 2.7 mg/L in children for the acute oral and intermediate dermal TRVs. The BE values derived in this manuscript can serve as a guide to help public health officials and regulators interpret population based DEET biomonitoring data in a public health risk context.

Deeper insights into the effects of low dietary levels of polychlorinated biphenyls on pig metabolism using gas chromatography-high resolution mass spectrometry metabolomics

Polychlorinated biphenyls (PCBs) are a class of contaminants of great concern, linked to the development of many chronic diseases. Adverse effects of PCBs have been documented in humans after accidental and massive exposure. However, little is known about the effect of chronic exposure to low-dose PCB mixtures, and studies regarding scattered lifetime exposures to non-dioxin-like (NDL)-PCBs are especially missing. In this work, serum samples from pigs chronically exposed through their diet during 22 days to Aroclor 1260 (i.e. a commercially available mixture of NDL-PCBs) underwent a metabolomics analysis using gas chromatography-high resolution mass spectrometry (GC-HRMS), with the objective to investigate the effect of exposure to low doses of NDL-PCBs (few ng/kg body weight (b.w.) per day). The study showed that the serum profiles of 84 metabolites are significantly altered by the administration of Aroclor 1260, of which 40 could be identified at level 1. The aggregate interpretation of the results of this study, together with the outcome of a previous one involving LC-HRMS profiling, provided a substantial and concise overview of the effect of low dose exposure to NDL-PCBs, reflecting the hepatotoxic and neurotoxic effects already reported in literature at higher and longer exposures. These results are intended to contribute to the debate on the current toxicological reference values for these substances.

Modification of the existing maximum residue levels for mefentrifluconazole in various commodities.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF Agro B.V. Arnhem (NL) Freienbach Branch submitted a request to the competent national authority in Austria to modify the existing maximum residue levels (MRLs) for the active substance mefentrifluconazole in various crops and swine liver and other swine products. The data submitted in support of the request were found to be sufficient to derive MRL proposals. Adequate analytical methods for enforcement are available to control the residues of mefentrifluconazole in the plant commodities under consideration and in animal matrices at the validated limit of quantification (LOQ) of 0.01 mg/kg. New data relevant to the data gaps on storage stability and feeding studies of triazole derivative metabolites (TDMs), that were identified during the peer review of confirmatory data of the TDMs, were submitted in support of the present MRL application. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of mefentrifluconazole according to the reported agricultural practices is unlikely to present a risk to consumer health. EFSA noted a narrow safety margin with regard to acute exposure to mefentrifluconazole residues from the intake of spinaches if residues occur at the level of the proposed MRL. EFSA also performed an indicative risk assessment for the TDMs based on uses of mefentrifluconazole only. The estimated exposure for TDMs did not exceed the toxicological reference values.

Reassessment of the cadmium toxicological reference value for use in human health assessments of foods

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 μg Cd/g creatinine for females aged 50–60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 μg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21–0.36 μg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63–1.8 μg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.