Pesticide residues in food - acute dietary exposure

Consumer risk assessment is a crucial step in the regulatory approval of pesticide use on food crops. Recently, an additional hurdle has been added to the formal consumer risk assessment process with the introduction of short-term intake or exposure assessment and a comparable short-term toxicity reference, the acute reference dose. Exposure to residues during one meal or over one day is important for short-term or acute intake. Exposure in the short term can be substantially higher than average because the consumption of a food on a single occasion can be very large compared with typical long-term or mean consumption and the food may have a much larger residue than average. Furthermore, the residue level in a single unit of a fruit or vegetable may be higher by a factor (defined as the variability factor, which we have shown to be typically ×3 for the 97.5th percentile unit) than the average residue in the lot. Available marketplace data and supervised residue trial data are examined in an investigation of the variability of residues in units of fruit and vegetables. A method is described for estimating the 97.5th percentile value from sets of unit residue data. Variability appears to be generally independent of the pesticide, the crop, crop unit size and the residue level. The deposition of pesticide on the individual unit during application is probably the most significant factor. The diets used in the calculations ideally come from individual and household surveys with enough consumers of each specific food to determine large portion sizes. The diets should distinguish the different forms of a food consumed, eg canned, frozen or fresh, because the residue levels associated with the different forms may be quite different. Dietary intakes may be calculated by a deterministic method or a probabilistic method. In the deterministic method the intake is estimated with the assumptions of large portion consumption of a ‘high residue’ food (high residue in the sense that the pesticide was used at the highest recommended label rate, the crop was harvested at the smallest interval after treatment and the residue in the edible portion was the highest found in any of the supervised trials in line with these use conditions). The deterministic calculation also includes a variability factor for those foods consumed as units (eg apples, carrots) to allow for the elevated residue in some single units which may not be seen in composited samples. In the probabilistic method the distribution of dietary consumption and the distribution of possible residues are combined in repeated probabilistic calculations to yield a distribution of possible residue intakes. Additional information such as percentage commodity treated and combination of residues from multiple commodities may be incorporated into probabilistic calculations. The IUPAC Advisory Committee on Crop Protection Chemistry has made 11 recommendations relating to acute dietary exposure.

A systematic review of the effect of dietary exposure that could be achieved through normal dietary intake on learning and performance of school-aged children of relevance to UK schools

The aim of the present review was to perform a systematic in-depth review of the best evidence from controlled trial studies that have investigated the effects of nutrition, diet and dietary change on learning, education and performance in school-aged children (4-18 years) from the UK and other developed countries. The twenty-nine studies identified for the review examined the effects of breakfast consumption, sugar intake, fish oil and vitamin supplementation and 'good diets'. In summary, the studies included in the present review suggest there is insufficient evidence to identify any effect of nutrition, diet and dietary change on learning, education or performance of school-aged children from the developed world. However, there is emerging evidence for the effects of certain fatty acids which appear to be a function of dose and time. Further research is required in settings of relevance to the UK and must be of high quality, representative of all populations, undertaken for longer durations and use universal validated measures of educational attainment. However, challenges in terms of interpreting the results of such studies within the context of factors such as family and community context, poverty, disease and the rate of individual maturation and neurodevelopment will remain. Whilst the importance of diet in educational attainment remains under investigation, the evidence for promotion of lower-fat, -salt and -sugar diets, high in fruits, vegetables and complex carbohydrates, as well as promotion of physical activity remains unequivocal in terms of health outcomes for all schoolchildren.

Market Basket Survey Shows Elevated Levels of As in South Central U.S. Processed Rice Compared to California: Consequences for Human Dietary Exposure:consequences for human dietary exposure

We report the largest market basket survey of arsenic (As) in U.S. rice to date. Our findings show differences in transitional-metal levels between polished and unpolished rice and geographical variation in As and selenium (Se) between rice processed in California and the South Central U.S. The mean and median As grain levels for the South Central U.S. were 0.30 and 0.27 µg As g-1, respectively, for 107 samples. Levels for California were 41% lower than the South Central U.S., with a mean of 0.17 µg As g-1 and a median of 0.16 µg As g-1 for 27 samples. The mean and median Se grain levels for the South Central U.S. were 0.19 µg Se g-1. Californian rice levels were lower, averaging only 0.08 and 0.06 µg Se g-1 for mean and median values, respectively. The difference between the two regions was found to be significant for As and Se (General Linear Model (GLM):? As p < 0.001; Se p < 0.001). No statistically significant differences were observed in As or Se levels between polished and unpolished rice (GLM:? As p = 0.213; Se p = 0.113). No significant differences in grain levels of manganese (Mn), cobalt (Co), copper (Cu), or zinc (Zn) were observed between California and the South Central U.S. Modeling arsenic intake for the U.S. population based on this survey shows that for certain groups (namely Hispanics, Asians, sufferers of Celiac disease, and infants) dietary exposure to inorganic As from elevated levels in rice potentially exceeds the maximum intake of As from drinking water (based on consumption of 1 L of 0.01 mg L-1 In. As) and Californian state exposure limits. Further studies on the transformation of As in soil, grain As bioavailability in the human gastrointestinal tract, and grain elemental speciation trends are critical.

Variation in arsenic speciation and concentration in Paddy Rice related to Dietary Exposure

Ingestion of drinking water is not the only elevated source of arsenic to the diet in the Bengal Delta. Even at background levels, the arsenic in rice contributes considerably to arsenic ingestion in subsistence rice diets. We set out to survey As speciation in different rice varieties from different parts of the globe to understand the contribution of rice to arsenic exposure. Pot experiments were utilized to ascertain whether growing rice on As contaminated soil affected speciation and whether genetic variation accounted for uptake and speciation. USA long grain rice had the highest mean arsenic level in the grain at 0.26 µg As g-1 (n = 7), and the highest grain arsenic value of the survey at 0.40 µg As g-1. The mean arsenic level of Bangladeshi rice was 0.13 µg As g-1 (n = 15). The main As species detected in the rice extract were AsIII, DMAV, and AsV. In European, Bangladeshi, and Indian rice 64 ± 1% (n = 7), 80 ± 3% (n = 11), and 81 ± 4% (n = 15), respectively, of the recovered arsenic was found to be inorganic. In contrast, DMAV was the predominant species in rice from the USA, with only 42 ± 5% (n = 12) of the arsenic being inorganic. Pot experiments show that the proportions of DMAV in the grain are significantly dependent on rice cultivar (p = 0.026) and that plant nutrient status is effected by arsenic exposure. Ingestion of drinking water is not the only elevated source of arsenic to the diet in the Bengal Delta. Even at background levels, the arsenic in rice contributes considerably to arsenic ingestion in subsistence rice diets. We set out to survey As speciation in different rice varieties from different parts of the globe to understand the contribution of rice to arsenic exposure. Pot experiments were utilized to ascertain whether growing rice on As contaminated soil affected speciation and whether genetic variation accounted for uptake and speciation. USA long grain rice had the highest mean arsenic level in the grain at 0.26 µg As g-1 (n = 7), and the highest grain arsenic value of the survey at 0.40 µg As g-1. The mean arsenic level of Bangladeshi rice was 0.13 µg As g-1 (n = 15). The main As species detected in the rice extract were AsIII, DMAV, and AsV. In European, Bangladeshi, and Indian rice 64 ± 1% (n = 7), 80 ± 3% (n = 11), and 81 ± 4% (n = 15), respectively, of the recovered arsenic was found to be inorganic. In contrast, DMAV was the predominant species in rice from the USA, with only 42 ± 5% (n = 12) of the arsenic being inorganic. Pot experiments show that the proportions of DMAV in the grain are significantly dependent on rice cultivar (p = 0.026) and that plant nutrient status is effected by arsenic exposure.

Dietary exposure to aflatoxin from maize and groundnut in young children from Benin and Togo, West Africa

Aflatoxins are a family of fungal toxins that are carcinogenic to man and cause immunosuppression, cancer and growth reduction in animals. We conducted a cross-sectional study among 480 children (age 9 months to 5 years) across 4 agroecological zones (SS, NGS, SGS and CS) in Benin and Togo to identify the effect of aflatoxin exposure on child growth and assess the pattern of exposure. Prior reports on this study [Gong, Y.Y., Cardwell, K., Hounsa, A., Egal, S., Turner, Hall, A.J., Wild, C.P., 2002. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. British Medical Journal 325, 20-21, Gong, Y.Y., Egal, S., Hounsa, A., Turner, P.C., Hall, A.J., Cardwell, K., Wild, C.P., 2003. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning and weaning foods. International Journal of Epidemiology, 32, 556-562] showed that aflatoxin exposure among these children is widespread (99%) and that growth faltering is associated with high blood aflatoxinalbumin adducts (AF-alb adducts), a measure of recent past exposure. The present report demonstrates that consumption of maize is an important source of aflatoxin exposure for the survey population. Higher AF-alb adducts were correlated with higher A. flavus (CFU) infestation of maize (p=0.006), higher aflatoxin contamination (ppb) of maize (p<0.0001) and higher consumption frequencies of maize (p=0.053). The likelihood of aflatoxin exposure from maize was particularly high in agro-ecological zones where the frequency of maize consumption (SGS and CS), the presence of allatoxin in maize (SGS) or the presence of A. flavus on maize (NGS and SGS) was relatively high. Socio-economic background did not affect the presence of A. flavus and aflatoxin in maize, but better maternal education was associated with lower frequencies of maize consumption among children from the northernmost agro-ecological zone (SS) (p=0.001). The impact of groundinit consumption on aflatoxin exposure was limited in this population. High AF-alb adduct levels were correlated with high prevalence of A. flavus and aflatoxin in groundinit, but significance was weak after adjustment for weaning status, agro-ecological zone and maternal socio-economic status (resp. p = 0.091 and p = 0.083). Ingestion of A. flavus and aflatoxin was high in certain agro-ecological zones (SS and SGS) and among the higher socio-economic strata due to higher frequencies of groundnut consumption. Contamination of groundnuts was similar across socio-economic and agroecological boundaries.

In conclusion, dietary exposure to aflatoxin from groundnut was less than from maize in young children from Benin and Togo. Intervention strategies that aim to reduce dietary exposure in this population need to focus on maize consumption in particular, but they should not ignore consumption of groundnuts. (c) 2005 Elsevier B.V. All rights reserved.

Dietary exposure to aflatoxin and fumonisin among Tanzanian children as determined using biomarkers of exposure

SCOPE: The study aims to evaluate the status of dietary exposure to aflatoxin and fumonisin in young Tanzanian children, using previously validated biomarkers of exposure. METHODS AND RESULTS: A total of 148 children aged 12-22 months, were recruited from three geographically distant villages in Tanzania; Nyabula, Kigwa, and Kikelelwa. Plasma aflatoxin-albumin adducts (AF-alb) and urinary fumonisin B1 (UFB1) were measured by ELISA and LC-MS, respectively. AF-alb was detectable in 84% of children, was highest in fully weaned children (p <0.01) with higher levels being associated with higher maize intake (p <0.05). AF-alb geometric mean (95% CI) was 43.2 (28.7-65.0), 19.9 (13.5-29.2), and 3.6 (2.8-4.7) pg/mg albumin in children from Kigwa, Nyabula, and Kikelelwa, respectively. UFB1 was detectable in 96% of children and the level was highest in children who had been fully weaned (p <0.01). The geometric UFB1 mean (95% CI) was 327.2 (217.1-493.0), 211.7 (161.1-278.1), and 82.8 (58.3-117.7) pg/mL in Kigwa, Nyabula, and Kikelelwa, respectively. About 82% of all the children were exposed to both mycotoxins. CONCLUSION: Young children in Tanzania are chronically exposed to both aflatoxin and fumonisin through contaminated diet, although the level of exposure varies markedly between the three villages studied.

FoodCAP: acid-labile protein adducts of heterocyclic amines in human blood are not viable biomarkers of HCA dietary exposure

Intake of heterocyclic amines (HCAs, carcinogens produced during cooking of meat/fish, the most abundant being PhIP, DiMeIQx and MeIQx) is influenced by many factors including type/thickness of meat and cooking method/temperature/duration. Thus, assessment of HCA dietary exposure is difficult. Protein adducts of HCAs have been proposed as potential medium-term biomarkers of exposure, e.g. PhIP adducted to serum albumin or haemoglobin. However, evidence is still lacking that HCA adducts are viable biomarkers in humans consuming normal diets. The FoodCAP project, supported by World Cancer Research Fund, developed a highly sensitive mass spectrometric method for hydrolysis, extraction and detection of acid-labile HCAs in blood and assessed their validity as biomarkers of exposure. Multiple acid/alkaline hydrolysis conditions were assessed, followed by liquid-liquid extraction, clean-up by cation-exchange SPE and quantification by UPLC-ESI-MS/ MS. Blood was analysed from volunteers who completed food diaries to estimate HCA intake based on the US National Cancer Institute’s CHARRED database. Standard HCAs were recovered quantitatively from fortified blood. In addition, PhIP/MeIQx adducts bound to albumin and haemoglobin prepared in vitro using a human liver microsome system were also detectable in blood fortified at low ppt concentrations. However, except for one sample (5pg/ml PhIP), acid-labile PhIP, 7,8-DiMeIQx, 4,8-DiMeIQx and MeIQx were not observed above the 2pg/ml limit of detection in plasma (n=35), or in serum, whole blood or purified albumin, even in volunteers with high meat consumption (nominal HCA intake >2µg/day). It is concluded that HCA blood protein adducts are not viable biomarkers of exposure. Untargeted metabolomic analyses may facilitate discovery of suitable markers.

Interventions Targeting Child Undernutrition in Developing Countries May Be Undermined by Dietary Exposure to Aflatoxin

Child undernutrition, a form of malnutrition, is a major public health burden in developing countries. Supplementation interventions targeting the major micronutrient deficiencies have only reduced the burden of child undernutrition to a certain extent, indicating that there are other underlying determinants that need addressed. Aflatoxin exposure, which is also highly prevalent in developing countries, may be considered to be an aggravating factor for child undernutrition. Increasing evidence suggests that aflatoxin exposure can occur in any stage of life including in utero through a trans-placental pathway and in early childhood (through contaminated weaning food and family food). Early life exposure to aflatoxin is associated with adverse effects on low birth weight, stunting, immune suppression and liver function damage. The mechanisms underlying impaired growth and aflatoxin exposure are still unclear but intestinal function damage, reduced immune function and alteration in the insulin-like growth factor axis caused by liver damage, are suggested hypotheses. Given the fact that both aflatoxin and child undernutrition are common in sub-Saharan Africa, effective interventions aimed at reducing undernutrition cannot be satisfactorily achieved until the interactive relationship between aflatoxin and child undernutrition is clearly understood, and an aflatoxin mitigation strategy has taken effect in those vulnerable mothers and children.

Dietary exposure to aflatoxin and micronutrient status among young children from Guinea

SCOPE: Aflatoxin exposure coincides with micronutrient deficiencies in developing countries. Animal feeding studies have postulated that aflatoxin exposure may be exacerbating micronutrient deficiencies. Evidence available in human subjects is limited and inconsistent. The aim of the study was to investigate the relationship between aflatoxin exposure and micronutrient status among young Guinean children.

METHOD AND RESULTS: A total of 305 children (28.8 ± 8.4 months) were recruited at groundnut harvest (rainy season), of which 288 were followed up 6 months later post-harvest (dry season). Blood samples were collected at each visit. Aflatoxin-albumin adduct levels were measured by ELISA. Vitamin A, vitamin E and β-carotene concentrations were measured using HPLC methods. Zinc was measured by atomic absorption spectroscopy. Aflatoxin exposure and micronutrient deficiencies were prevalent in this population and were influenced by season, with levels increasing between harvest and post-harvest. At harvest, children in the highest aflatoxin exposure group, compared to the lowest, were 1.98 (95%CI: 1.00, 3.92) and 3.56 (95%CI: 1.13, 11.15) times more likely to be zinc and vitamin A deficient.

CONCLUSION: Although children with high aflatoxin exposure levels were more likely to be zinc and vitamin A deficient, further research is necessary to determine a cause and effect relationship. 

Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study.

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA-protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1e5 pg/ml plasma and recoveries 91e115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid-labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA peptide markers and use of untargeted proteomic and metabolomic approaches.

Long-term dietary exposure to lead in young European children: comparing a pan-European approach with a national exposure assessment

Long-term dietary exposures to lead in young children were calculated by combining food consumption data of 11 European countries categorised using harmonised broad food categories with occurrence data on lead from different Member States (pan-European approach). The results of the assessment in children living in the Netherlands were compared with a long-term lead intake assessment in the same group using Dutch lead concentration data and linking the consumption and concentration data at the highest possible level of detail. Exposures obtained with the pan-European approach were higher than the national exposure calculations. For both assessments cereals contributed most to the exposure. The lower dietary exposure in the national study was due to the use of lower lead concentrations and...

Gender-specific modulation of immune system complement gene expression in marine medaka Oryzias melastigma following dietary exposure of BDE-47

BDE-47 is one of the most widely found congeners of PBDEs in marine environments. The potential immunomodulatory effects of BDE-47 on fish complement system were studied using the marine medaka Oryzias melastigma as a model fish. Three-month-old O. melastigma were subjected to short-term (5 days) and long-term (21 days) exposure to two concentrations of BDE-47 (low dose at 290 +/- 172 ng/day; high dose at 580 +/- 344 ng/day) via dietary uptake of BDE-47 encapsulated in Artemia nauplii. Body burdens of BDE-47 and other metabolic products were analyzed in the exposed and control fish. Only a small amount of debrominated product, BDE-28, was detected, while other metabolic products were all under detection limit. Transcriptional expression of six major complement system genes involved in complement activation: C1r/s (classical pathway), MBL-2 (lectin pathway), CFP (alternative pathway), F2 (coagulation pathway), C3 (the central component of complement system), and C9 (cell lysis) were quantified in the liver of marine medaka. Endogenous expression of all six complement system genes was found to be higher in males than in females (p < 0.05). Upon dietary exposure of marine medaka to BDE-47, expression of all six complement genes were downregulated in males at day 5 (or longer), whereas in females, MBl-2, CFP, and F2 mRNAs expression were upregulated, but C3 and C9 remained stable with exposure time and dose. A significant negative relationship was found between BDE-47 body burden and mRNA expression of C1r/s, CFP, and C3 in male fish (r = -0.8576 to -0.9447). The above findings on changes in complement gene expression patterns indicate the complement system may be compromised in male O. melastigma upon dietary exposure to BDE-47. Distinct gender difference in expression of six major complement system genes was evident in marine medaka under resting condition and dietary BDE-47 challenge. The immunomodulatory effects of BDE-47 on transcriptional expression of these complement components in marine medaka were likely induced by the parent compound instead of biotransformed products. Our results clearly demonstrate that future direction for fish immunotoxicology and risk assessment of immunosuppressive chemicals must include parallel evaluation for both genders.

Urinary excretion of cadmium among Torres Strait Islanders (Australia) at risk of elevated dietary exposure through traditional foods

This study explored urinary cadmium levels among Torres Strait Islanders in response to concerns about potential health impact of high levels of cadmium in some traditional seafood (dugong and turtle liver and kidney). Cadmium levels were measured by inductively coupled mass spectrometry in de-identified urine samples collected during general screening programs in 1996 in two communities with varying dugong and turtle catch statistics. Statistical analysis was performed to identify links between cadmium levels and demographic and background health information. Geometric mean cadmium level among the sample group was 0.83 mu g/g creatinine with 12% containing over 2 mu g/g creatinine. Cadmium level was most strongly associated with age (46% of variation), followed by sex (females > males, 7%) and current smoking status (smokers > non-smokers, 4.7%). Adjusting model conditions suggested further positive associations between cadmium level and diabetes (p = 0.05) and residence in the predicted higher exposure community (p = 0.07). Positive correlations between cadmium and body fat in bivariate analysis were eliminated by control for age and sex. This study found only suggestive differences in cadmium levels between two communities with predicted variation in exposure from traditional foods. However, the data indicate that factors linked with higher cadmium accumulation overlap with those of renal disease risk (i.e. older, females, smokers, diabetes) and suggest that levels may be sufficient to contribute to renal pathology. More direct assessment of exposure and health risks of cadmium to Torres Strait Islanders is needed given the disproportionate level of diet-related disease and the cultural importance of dugong and turtle. This study highlights the need to consider social and cultural variation in exposure and to de. ne "safe'' cadmium levels during diabetes given its rising global prevalence.

Dietary exposure assessments for children in Europe (the EXPOCHI project): rationale, methods and design

[EN]The number of dietary exposure assessment studies focussing on children is very limited. Children are however a vulnerable group due to their higher food consumption level per kg body weight. Therefore, the EXPOCHI project aims [1] to create a relational network of individual food consumption databases in children, covering different geographical areas within Europe, and [2] to use these data to assess the usual intake of lead, chromium, selenium and food colours.