Prioritisation of pesticides and target organ systems for dietary cumulative risk assessment based on the 2019-2021 monitoring cycle.

Aiming at accelerating the implementation of cumulative risk assessment to pesticide residues, this report describes a two-step prioritisation analysis, on individual pesticides and on target organ systems, that allows to identify (i) low-priority substances expected to have a marginal contribution to cumulative risk, and (ii) high priority organ systems to be addressed in future cumulative risk assessments. The analysis encompassed 350 substances and 36 raw primary commodities of plant origin surveyed in the monitoring cycle 2019-2021, carried out in 30 population groups, covering 3 age classes, and 17 EU countries. Probabilistic exposure calculations, for chronic and acute effects, were executed on the occurrence and consumption data by a two-dimensional procedure, modelling variability and uncertainty. In the first step, the prioritisation method adopted allowed to reduce the number of substances by about 80%. These substances were in turn grouped based on their capacity to cause toxicological effects on common organ systems and, as second step, probabilistic combined exposure calculations were carried out for 16 target organ systems. This step allowed to identify the organ systems that need further assessment, reducing their initial number by about 70%. The organ systems would need to be prioritised as follows: reproductive and developmental toxicity, liver, kidney, male reproductive system, and haematopoietic system and haematology. The sources of uncertainty stemming from the modelling procedure and from methodological assumptions were discussed and their impact qualitatively assessed. Overall, it was concluded that the risk estimates for the different organ systems were more likely to be overestimated than underestimated.

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.

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

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.

Cumulative dietary risk characterisation of pesticides that have acute effects on the nervous system.

A retrospective acute cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, and functional alterations of the motor division. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the acute effects on the nervous system mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

Cumulative dietary risk characterisation of pesticides that have chronic effects on the thyroid.

A retrospective chronic cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the thyroid, hypothyroidism and parafollicular cell (C-cell) hypertrophy, hyperplasia and neoplasia. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the thyroid. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the chronic effects on the thyroid mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

Cumulative dietary exposure assessment of pesticides that have chronic effects on the thyroid using SAS® software.

Retrospective dietary exposure assessments were conducted for two groups of pesticides that have chronic effects on the thyroid: hypertrophy, hyperplasia and neoplasia of C-cells, and hypothyroidism. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the thyroid. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained for each group of pesticides by means of a 2-dimensional probabilistic model, which was implemented in SAS ® software. Results were validated against exposure estimates obtained by the Dutch National Institute for Public Health and the Environment (RIVM) using the Monte Carlo Risk Assessment (MCRA) software. Both tools produced nearly identical results and minor differences were mainly attributed to the random effect of probabilistic modelling. The exposure estimates obtained in this report are used in the final scientific report on the cumulative dietary risk characterisation of pesticides that have chronic effects on the thyroid. The latter combines the hazard assessment and exposure assessment into a consolidated risk characterisation including all uncertainties.

Cumulative dietary exposure assessment of pesticides that have acute effects on the nervous system using SAS® software.

Retrospective dietary exposure assessments were conducted for two groups of pesticides that have acute effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, and functional alterations of the motor division. The pesticides considered in this assessment were identified and characterised in the 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 2014, 2015 and 2016 and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained for each group of pesticides by means of a 2-dimensional Monte Carlo simulation, which was implemented in SAS ® software. Results were validated against exposure estimates obtained by the Dutch National Institute for Public Health and the Environment (RIVM) using the Monte Carlo Risk Assessment (MCRA) software. Both tools produced nearly identical results and minor differences were mainly attributed to the random effect of probabilistic modelling. The exposure estimates obtained in this report are used in the final scientific report on the cumulative dietary risk characterisation of pesticides that have acute effects on the nervous system. The latter combines the hazard assessment and exposure assessment into a consolidated risk characterisation including all related uncertainties.

Effect on public health of a possible increase of the maximum level for 'aflatoxin total' from 4 to 10 µg/kg in peanuts and processed products thereof, intended for direct human consumption or use as an ingredient in foodstuffs.

EFSA was asked to deliver a scientific opinion regarding the effect on public health of a possible increase of the maximum level (ML) for 'aflatoxin total' (AFT; sum of aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2) from 4 to 10 µg/kg in peanuts and processed products thereof. Aflatoxins are genotoxic and cause hepatocellular carcinomas in humans. The Panel on Contaminants in the Food Chain (CONTAM Panel) evaluated 8,085 samples of peanuts and 472 samples of peanut butter, with > 60% left-censored. The mean concentration of AFT in peanuts was 2.65/3.56 µg/kg (lower bound (LB)/upper bound (UB)) with a maximum of 1,429 µg/kg. The mean concentration in peanut butter was 1.47/1.92 µg/kg (LB/UB) with a maximum of 407 µg/kg. Peanut oil was not included since all data were left-censored and the ML does not apply for oil. Exposure was calculated for a 'Current ML' and 'Increased ML' scenario, and mean chronic exposure estimates for consumers only, amounted to 0.04-2.74 ng/kg body weight (bw) per day and 0.07-4.28 ng/kg bw per day, respectively. The highest exposures were calculated for adolescents and other children. The CONTAM Panel used the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives for the risk characterisation. Under the scenario of the current ML, the cancer risk was estimated to range between 0.001 and 0.213 aflatoxin-induced cancers per 100,000 person years. Under the scenario of the increased ML, it ranged between 0.001 and 0.333 aflatoxin-induced cancers per 100,000 person years. Comparing these data calculated under the current ML scenario with the yearly excess cancer risk of 0.014 shows a higher risk for consumers of peanuts and peanut butter in some surveys. The calculated cancer risks indicate that an increase of the ML would further increase the risk by a factor of 1.6-1.8.

Scientific opinion on pesticides in foods for infants and young children.

Following a request from the European Commission, the EFSA Panel on Plant Protection Products and their Residues (PPR Panel) prepared a scientific opinion to provide a comprehensive evaluation of pesticide residues in foods for infants and young children. In its approach to develop this scientific opinion, the EFSA PPR Panel took into account, among the others, (i) the relevant opinions of the Scientific Committee for Food setting a default maximum residue level (MRL) of 0.01 mg/kg for pesticide residues in foods for infants and young children; (ii) the recommendations provided by EFSA Scientific Committee in a guidance on risk assessment of substances present in food intended for infants below 16 weeks of age; (iii) the knowledge on organ/system development in infants and young children. For infants below 16 weeks of age, the EFSA PPR Panel concluded that pesticide residues at the default MRL of 0.01 mg/kg for food for infants and young children are not likely to result in an unacceptable exposure for active substances for which a health-based guidance value (HBGV) of 0.0026 mg/kg body weight (bw) per day or higher applies. Lower MRLs are recommended for active substances with HBGVs below this value. For infants above 16 weeks of age and young children, the established approach for setting HBGVs is considered appropriate. For infants below 16 weeks of age the approach may not be appropriate and the application of the EFSA guidance on risk assessment of substances present in food intended for infants below 16 weeks of age is recommended. The contribution of conventional food to the total exposure to pesticide residues is much higher than that from foods intended for infants and young children. Because of the increased intake of conventional food by young children, these have the highest exposure to pesticide residues, whereas infants 3-6 months of age generally have lower exposure. The impact of cumulative exposure to pesticide residues on infants and young children is not different from the general population and the EFSA cumulative risk assessment methodology is also applicable to these age groups. Residue definitions established under Regulation (EC) No 396/2005 are in general considered appropriate also for foods for infants and young children. However, based on a tier 1 analysis of the hydrolysis potential of pesticides simulating processing, the particular appropriateness of existing residue definitions for monitoring to cover processed food, both intended for infants and young children as well as conventional food, is questionable.

Risks for public health related to the presence of furan and methylfurans in food.

The European Commission asked EFSA for a scientific evaluation on the risk to human health of the presence of furan and methylfurans (2-methylfuran, 3-methylfuran and 2,5-dimethylfuran) in food. They are formed in foods during thermal processing and can co-occur. Furans are produced from several precursors such as ascorbic acid, amino acids, carbohydrates, unsaturated fatty acids and carotenoids, and are found in a variety of foods including coffee and canned and jarred foods. Regarding furan occurrence, 17,056 analytical results were used in the evaluation. No occurrence data were received on methylfurans. The highest exposures to furan were estimated for infants, mainly from ready-to-eat meals. Grains and grain-based products contribute most for toddlers, other children and adolescents. In adults, elderly and very elderly, coffee is the main contributor to dietary exposure. Furan is absorbed from the gastrointestinal tract and is found in highest amounts in the liver. It has a short half-life and is metabolised by cytochrome P450 2E1 (CYP2E1) to the reactive metabolite, cis-but-2-ene-1,4-dialdehyde (BDA). BDA can bind covalently to amino acids, proteins and DNA. Furan is hepatotoxic in rats and mice with cholangiofibrosis in rats and hepatocellular adenomas/carcinomas in mice being the most prominent effects. There is limited evidence of chromosomal damage in vivo and a lack of understanding of the underlying mechanism. Clear evidence for indirect mechanisms involved in carcinogenesis include oxidative stress, gene expression alterations, epigenetic changes, inflammation and increased cell proliferation. The CONTAM Panel used a margin of exposure (MOE) approach for the risk characterisation using as a reference point a benchmark dose lower confidence limit for a benchmark response of 10% of 0.064 mg/kg body weight (bw) per day for the incidence of cholangiofibrosis in the rat. The calculated MOEs indicate a health concern. This conclusion was supported by the calculated MOEs for the neoplastic effects.

[Audit of the quality of treatment of "near miss" patients in referral maternities in Southern Benin]. / Audit de la qualité de prise en charge des << échappées belle >> (near miss) dans les maternités de référence du Sud Bénin.

OBJECTIVES: Maternal mortality is highly associated with the provision of obstetric care. The provision of safe and timely emergency obstetric care (EOC) for women with severe obstetric complications is one of the main components of safe motherhood programs. In this research the objective was to determine the quality of EOC by examining its availability and its provision in a timely fashion. DESIGN: prospective observational study in qualified facilities providing EOC. SETTING: two teaching, two regional and three district hospitals in the southern part of Benin, West Africa. METHOD: The study was conducted from July to October 2003. Data collection tools used were based on the World Health organisation Guidelines for monitoring EOC. The midwives in charge of the survey started observation from the admission room and followed the provision of the care offered to the women admitted with near miss complications until they were discharged from hospital. The information about EOC, its availability, timeliness and patients' follow-up were recorded. RESULTS: The study sample included 557 women; immediate emergency care was given within 30 minutes for 61% of the patients. Surgical care (caesarean section and ectopic pregnancies surgery) was started within 60 minutes for 42% and 45 % of the women. In the near miss cases suffering anaemia, blood was not available for 12% of patients and blood transfusions were started within 60 minutes in 10% of cases. In the case of uterine rupture or pre-rupture, the time for starting caesarean section was 60 minutes for 58% of women. As to haemorrhagic near-miss cases, blood was not available in 44% of cases and if caesarean section was indicated, it was done within 60 minutes in 47% of the cases. Half of the patients with hypertension received treatment within 60 minutes after the decision to do so was taken. In infection cases, 53% of the patients received antibiotics treatment within 60 minutes. Generally, the quality of providing EOC in the facilities of the study was good in only 16.4% of cases. The quality of care was good in 31.4% of the cases with dystocia, 19% of the cases with hypertension, in 18% of the cases with haemorrhage, in 13.4% of the cases with infection, and in 6.4% of the cases with anaemia. CONCLUSION: Our study has shown that, often, EOC was not provided in a timely fashion. A reflection with all the health providers involved should lead to a better understanding of better ways to improve the quality of EOC.

Informing the TB suspect for sputum sample collection and communicating laboratory results in Nicaragua: a neglected process in tuberculosis case finding

OBJETIVO: valorar el proceso de información del paciente antes de la producción de esputo, la calidad de la muestra de esputo, y la transmisión de los resultados del examen microscópico del esputo a los sospechosos de tuberculosis (TB) en tres áreas de Nicaragua. MATERIAL Y MÉTODOS: (a) entrevistas dirigidas a sospechosos de TB cuya expectoración ha sido examinada para BK; (b) entrevistas dirigidas al personal de salud de tres áreas de estudio (c) la evaluación de la calidad de la expectoración. RESULTADOS: Un total de 115 sospechosos de TB y 33 trabajadores de la salud fueron entrevistados; 625 muestras de esputo fueron examinadas. Los resultados muestran varias debilidades en el proceso de información a los sospechosos antes de la producción de esputo. CONCLUSIÓN: Este estudio revela un aspecto del proceso de diagnóstico de la TB demasiado ignorado. Los resultados ilustran la importancia de evaluar de forma rutinaria el proceso completo de diagnóstico de la TB. Informing the TB suspect for sputum sample collection and communicating laboratory results in Nicaragua: a neglected process in tuberculosis case finding.

[The efficiency of different detection strategies of human African trypanosomiasis by T. b. gambiense]. / Efficience de differentes strategies de detection de la Trypanosomiase Humaine Africaine aT. b. gambiense.

INTRODUCTION: Population screening for human African trypanosomiasis (HAT) is often based on a combination of two screening tests: lymph node palpation (LN) and card agglutination test for trypanosomiasis (CATT). This decision analysis compared the efficiency of three alternative detection strategies: screening by LN only, CATT only and their combination (LN and CATT). METHOD: An HAT detection strategy was defined as the sequence of screening and confirmation. Efficacy was evaluated in terms of lives saved. The cost of screening and confirmation tests was estimated in US$. The different parameters in the decision tree were based on published literature and observations of the HAT control programme in the Democratic Republic of Congo. A sensitivity analysis was carried out on those parameters subject to uncertainty. RESULTS: The cost-effectiveness of a detection strategy based on CATT was US $125 per life saved, compared with US $517 for LN and US $452 for the combined. Marginal cost to add LN to CATT only was between US $1225 and US $5000 per life saved. Sensitivity analysis shows that these results are robust to variation. DISCUSSION: The CATT strategy was the most efficient. None of the strategies was able to avoid more than 60% of HAT deaths. This moderate efficacy is due to the low sensitivity of the confirmatory (diagnostic) tests. Substantial efficiency gains can be obtained by adopting a CATT only strategy and resources can be better allocated to more sensitive confirmatory tests or to increasing the coverage of populations at risk.

[The prepayment scheme in Rwanda (II): membership and use of services by beneficiaries]. / Le système de prépaiement au Rwanda (II): adhésion et utilisation des services par les bénéficiaires.

In Rwanda, the Ministry of Health is rebuilding the health sector destroyed during the genocide while trying to guarantee the financial accessibility of the population to the services through the setting up of a prepayment scheme. Membership remains low in the three pilot districts where the prepayment scheme was introduced four years before (15,6%). In two of these districts, the curative consultation and maternity utilisation has increased appreciably. The members of the prepayment scheme make greater use of the services than the rest of the population. There is a significantly higher prepayment scheme membership among households with a relatively high income and those with a large family (more than 5 family members). Overall, non-members of the prepayment scheme spend more on health services than members do. There are indications that developing the prepayment scheme would be very useful for the people in Rwanda if specific strategies geared to the poor were set up.

[The prepayment scheme in Rwanda (I): analysis of a pilot experiment]. / Le système de prépaiement au Rwanda (I): analyse d'une expérience pilote.

Rwanda has made the setting up of a prepayment scheme a priority in its health sector reform in order to make health services more financially accessible to the population. A pilot study was carried out in three districts. The yearly family subscription charge was fixed at 7.9 US dollars, which covers care delivered at Health Centre level as well as some services at the hospital. The beneficiaries and providers mention difficulties in order to mobilise the subscription charges all at a time, the insufficiency of the offer of services at the hospital and the absence of involvement of the political authorities in the process. The Ministry of Health did initiate the experiment but the choice of the privileged pilot districts prevents results from being extrapolated to the country taken as a whole with a view to a possible extension at a later stage. Given the relatively short time in which it has taken place, the population could neither understand the contingency and solidarity issues implied nor have the opportunity to feel personally involved in the system. As a conclusion, the study advocates the continuation of the experiment with a reinforcement of the coordination which should take the weak points identified into account.