The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls.

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Phthalate and BPA Exposure in Women and Newborns through Personal Care Product Use and Food Packaging.

Phthalates and bisphenol A (BPA) are used in some personal care products (PCPs) and containers for food processing and packaging. The Plastics and Personal-Care Product use in Pregnancy (P4) Study (2009-10) explored the association between PCP use during pregnancy and the postpartum period among 80 pregnant women and 55 infants and BPA and phthalate concentrations in multiple maternal and infant urine specimens collected throughout the study (n = 1260 samples). The type, frequency, and timing of PCP and food packaging use 24 h before and during the urine collection period was collected at 5 time points for the mother using prospective diaries. Infant urine was collected up to 2 times before 3 months of age, and mothers answered questions about infant feeding and PCP use on their baby. In mothers, monoethyl phthalate (MEP) metabolite concentrations were significantly higher when women reported using makeup or body lotion in the last 24 h. MEP concentrations were consistently higher when the usage occurred within 0-6 h before the urine sample collection for almost all of the PCP categories. Infant lotion or baby powder application in the previous 24 h was associated with higher phthalate metabolite concentrations in infants. Total BPA metabolite concentrations were lower in exclusively breastfed infants compared to those who were exclusively formula fed or breastfed with supplementation. Given that PCPs tend to undergo frequent formulation changes, which could impact the relative importance of a certain product type as a source of exposure, continued research of this type is warranted.

Development of Biomonitoring Equivalents for chlordane and toxaphene with application to the general Canadian population.

Biomonitoring Equivalents (BEs) were developed for chlordane and toxaphene using one-compartment pharmacokinetic models and compared with biomonitoring data from the Canadian Health Measures Survey, Cycle 1 (2007-2009). A secondary objective was to examine the toxicities of the components of technical chlordane in a HEPG2 cell culture experiment. Oral reference doses were identified from national and international regulatory agencies and sources. Pharmacokinetic parameters were obtained from experimental data in rodent models. A set of BEs have been derived for the main chlordane isomers, cis-chlordane, trans-chlordane, cis-nonachlor, and trans-nonachlor, and the chlordane metabolite, oxychlordane. BEs were also derived for the main toxaphene isomers found in biota, Parlar No. 26, 50 and 62. Among the general Canadian population, no exceedances of chlordane or toxaphene BEs were observed. Based on the LC50 from the in vitro study, trans-nonachlor was the most toxic, and the trans-isomers were more toxic than the cis-isomers. The derived BE values can be used as screening guidelines to assess the risk of biomonitoring data in human populations. The results of an in vitro experiment suggest that trans-nonachlor is more toxic than technical chlordane and, therefore, the BE for this compound may need to be further lowered.

Paraben Concentrations in Maternal Urine and Breast Milk and Its Association with Personal Care Product Use.

Parabens are broad-spectrum antimicrobial preservatives and fragrances used in a wide range of personal care products, pharmaceuticals, and food providing the opportunity for people to be exposed on a daily basis. In 2009-2010, 80 pregnant women from Ottawa Canada participated in the Plastics and Personal-Care Product Use in Pregnancy (P4) Study. A subset of women (n = 31) who provided multiple spot urine samples (n = 542) collected over two 24-h periods had their samples analyzed for methylparaben (MP), n-propylparaben (PP), ethylparaben (EP), butylparaben (BP), isobutylparaben (IBP), and benzylparaben (BzP). These parabens were also measured in breast milk samples collected at approximately 3 months postpartum (n = 56 women). Women kept a diary of products that they used 24 h prior to and during the collection. All parabens measured in maternal urine had moderate to high reproducibility. Women who used lotions in the past 24 h had significantly higher geometric mean paraben concentrations (80-110%) in their urine than women who reported no use in the past 24 h. Women who used shampoo, conditioner, and cosmetics also showed 70-80% higher BP concentrations in their urine. Breast milk samples had >50% detection for MP, PP, and EP.

Urinary and breast milk biomarkers to assess exposure to naphthalene in pregnant women: an investigation of personal and indoor air sources.

BACKGROUND: Naphthalene exposures for most non-occupationally exposed individuals occur primarily indoors at home. Residential indoor sources include pest control products (specifically moth balls), incomplete combustion such as cigarette smoke, woodstoves and cooking, some consumer and building products, and emissions from gasoline sources found in attached garages. The study aim was to assess naphthalene exposure in pregnant women from Canada, using air measurements and biomarkers of exposure. METHODS: Pregnant women residing in Ottawa, Ontario completed personal and indoor air sampling, and questionnaires. During pregnancy, pooled urine voids were collected over two 24-hour periods on a weekday and a weekend day. At 2-3 months post-birth, they provided a spot urine sample and a breast milk sample following the 24-hour air monitoring. Urines were analyzed for 1-naphthol and 2-naphthol and breast milk for naphthalene. Simple linear regression models examined associations between known naphthalene sources, air and biomarker samples. RESULTS: Study recruitment rate was 11.2% resulting in 80 eligible women being included. Weekday and weekend samples were highly correlated for both personal (r = 0.83, p < 0.0001) and indoor air naphthalene (r = 0.91, p < 0.0001). Urine specific gravity (SG)-adjusted 2-naphthol concentrations collected on weekdays and weekends (r = 0.78, p < 0.001), and between pregnancy and postpartum samples (r = 0.54, p < 0.001) were correlated.Indoor and personal air naphthalene concentrations were significantly higher post-birth than during pregnancy (p < 0.0001 for signed rank tests); concurrent urine samples were not significantly different. Naphthalene in breast milk was associated with urinary 1-naphthol: a 10% increase in 1-naphthol was associated with a 1.6% increase in breast milk naphthalene (95% CI: 0.2%-3.1%). No significant associations were observed between naphthalene sources reported in self-administered questionnaires and the air or biomarker concentrations. CONCLUSIONS: Median urinary concentrations of naphthalene metabolites tended to be similar to (1-naphthol) or lower (2-naphthol) than those reported in a Canadian survey of women of reproductive age. Only urinary 1-naphthol and naphthalene in breast milk were associated. Potential reasons for the lack of other associations include a lack of sources, varying biotransformation rates and behavioural differences over time.

Risk assessment supporting the establishment of a maximum residue limit for ractopamine in beef liver, applicable in the Arab Republic of Egypt.

In 2012, the Codex Alimentarius Commission adopted maximum residue limits (MRLs) for ractopamine in pig and cattle tissues. Egypt, a country that records a high consumption of beef liver, conducted a health risk assessment to estimate the risks associated with the adoption of Codex MRLs and the possible adoption of alternative values that may offer higher protection. Ractopamine was characterized based on previous assessments performed by international regulatory agencies, and an acceptable daily intake was set at 1 µg/kg bw for both chronic and acute ractopamine exposure. Beef liver consumption data for the Egyptian population were collected through a field survey (529 households, 1929 individuals). The standard body weight of 60 kg was used, as well as 70 kg, as a potentially more representative weight for the Egyptian population. Simulations showed that when the MRL for ractopamine in beef liver is set to 40 µg/kg (Codex MRL) or 20 µg/kg, the health-based guidance value of 1 µg/kg bw was not exceeded, as a result of chronic or acute exposure. An MRL of 20 µg/kg of ractopamine in beef liver was shown to provide optimum protection of Egyptian consumers, considering other potential sources of ractopamine intake and abnormally high consumption patterns, and was therefore recommended for adoption in Egypt. This study presents the inputs, model, and results of the probabilistic risk assessment that supported such recommendation. PRACTICAL APPLICATION: Residues of veterinary drugs, such as ractopamine, accumulate in animal tissues and may pose a risk to consumers. Establishing maximum residue limits (MRLs) will help importers by giving them the necessary visibility for commercial trade. It will also benefit Egyptian consumers, large consumers of beef liver, who will be better protected with a lower MRL than the internationally recommended one.

Methylmercury blood guidance values for Canada.

Exposure to methylmercury (MeHg) from fish and marine mammal consumption continues to present a public health concern. To date, developmental neurotoxicity is the most sensitive health outcome, forming the basis for health-risk assessments and the derivation of biomonitoring guidance values. This article summarizes existing Health Canada MeHg blood guidance values for general population and expands them to include a harmonized provisional interim blood guidance value of 8 microg/L based on the existing provisional Tolerable Daily Intake for children, pregnant women and women of childbearing age. Associated public health actions, according to age, sex, and level of exposure are recommended.

Polychlorinated Biphenyls and Polychlorinated Dioxins-Furans in Lake Trout and Whitefish Composite Samples from Commercial Fisheries in Lakes Erie, Huron, and Superior.

Polychlorinated biphenyls (PCBs; sum of 36 congeners) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs; sum of 17 2,3,7,8-substituted congeners) were measured in 93 composite samples prepared from individual lake trout (Salvelinus namaycush) and whitefish (Coregonus clupeaformis) samples collected from Lake Erie, Lake Huron, and Lake Superior. All samples had detectable concentrations of PCBs and PCDD/Fs; maximum PCB concentrations in both trout (750 ng g-1 whole weight [ww]) and whitefish (210 ng g-1 ww) were found in composites from fish collected from Lake Huron. The maximum toxic equivalent concentration was found in a lake trout composite sample from Lake Huron (53 pg g-1 ww). PCB and PCDD/F congener profiles were comparable to patterns observed in fishes collected from other regions of Canada, although concentrations were above those found in other regions. A positive correlation was found between PCB concentrations determined using the historical Aroclor equivalency method and those determined using the sum of the congeners measured (r2 = 0.871; Spearman correlation r = 0.917) or using the six indicator PCB congeners (28, 52, 101, 138, 153, and 180; r2 = 0.850; Spearman correlation r = 0.935). PCBs were the dominant contributor to the overall toxic equivalent concentrations in the fish composite samples tested. These findings provide insight into PCB and PCDD/F concentrations in two commercially important fish species over a discrete time period.

The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds.

In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden.

Maternal and early life exposure to phthalates: The Plastics and Personal-care Products use in Pregnancy (P4) study.

Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n-octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates.

Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines.

The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated the relationship with organochlorine body burden in adult volunteers from this population. We determined plasma concentrations of PCBs and chlorinated pesticides by high-resolution gas chromatography (HRGC) with electron capture detection. DLC concentrations were measured by the dioxin-receptor chemically activated luciferase expression (DR-CALUX) assay and in a subset of participants, by HRGC/high-resolution mass spectrometry. We measured cotinine, d-glucaric acid, and porphyrins in morning urine samples and determined liver CYP1A2 activity in vivo using the caffeine breath test. Neither DLC concentrations as measured by the DR-CALUX nor PCB-153 concentrations, the latter representing total PCB exposure, were correlated with biomarkers of effects. Smoking (morning urinary cotinine concentration) was positively related to CYP1A2 activity as measured by the caffeine breath test (p < 0.01). Liver CYP1A2 activity was in turn negatively correlated with PCB-105:PCB-153 and PCB-118:PCB-153 congener ratios (p < 0.05). Hence, despite the relatively high body burden of PCBs and DLCs in this population, only smoking had a significant correlation with biomarkers of hepatic enzyme induction. Our data are consistent with smoking-induced liver CYP1A2 activity altering heme metabolism and increasing the biotransformation of mono-ortho PCB congeners.

Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability.

Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.

Maternal and infant exposure to environmental phenols as measured in multiple biological matrices.

BACKGROUND: Results of recent national surveys have shown the high prevalence of exposure to bisphenol A (BPA) and triclosan (TCS) among the general population; however biomonitoring data for pregnant women and infants are limited. METHODS: Women (n=80) were recruited from early prenatal clinics and asked to collect urine samples multiple times during pregnancy and once 2-3 months post-partum. Samples of infant urine and meconium as well as breast milk and infant formula were also collected. Biospecimens were analyzed by GC-MS/MS for BPA, TCS and triclocarban (TCC). RESULTS: Triclosan was detected in over 80% of the maternal urines (geometric mean (GM): 21.61 µg/L), 60% of the infant urines (GM: 2.8 µg/L), 46% of the breast milk and 80% of the meconium samples. Triclocarban was rarely detected in any of the biospecimens. Median total BPA concentrations were 1.21 and 0.24 µg/L in maternal and infant urines, respectively. Free BPA was detected in only 11% of infant urine samples. The meconium of female infants had significantly higher concentrations of total BPA and TCS than those of males, while no differences were observed in infant urine concentrations by sex. CONCLUSIONS: We found widespread exposure among pregnant women and infants to environmental phenols, with large inter-individual variability in exposure to triclosan. These data will contribute to the risk assessment of these chemicals, especially in susceptible sub-populations.

Polybrominated diphenyl ethers: human tissue levels and toxicology.

PBDEs are being released to the environment in wastes from their production facilities, degradation, or leaching and volatilization from products that contain PBDEs during the product's useful life. Brominated diphenyl ether congeners BDE-47, -99, and -153 are ubiquitous in the environment and are regarded as the most dominant congeners present in wildlife and humans. The tetra- to hexa-BDE are most likely the congeners to which humans are exposed through food consumption. Knowledge of PBDE uptake, metabolism, elimination, and enzyme induction is restricted largely to rodents (rats and mice) in vitro and in vivo. Feeding studies have shown that excretion of higher brominated BDEs is much greater than lower brominated BDEs. Penta-BDE is more toxic than octa- and deca-BDE following oral administration (oral LD50 in rats, 0.5-5 g/kg). In rodents, repeated exposure to PBDEs results in thyroid hormone disruption, developmental neurotoxicity, some changes of fetal development, and hepatotoxic effects. The observed chronic NOELs depend upon the technical mixture type (i.e., deca-, octa-, or penta- and their congener composition), animal species, and study protocol. Values range from 0.6 to 100 mg/kg in rats and from I to 100 mg/kg in mice. PBDEs are neither mutagenic nor genotoxic. Immunotoxicity in mice is observed following exposure to BDE-47 at 18 mg/kg/d, where splenocyte number decreased. Mice exposed neonatally to a single oral dose of BDE-47(10.5 mg/kg) or BDE-99 (12 mg/kg) on Pnd10 (period of rapid brain growth and development) show permanent impairment of spontaneous motor behavior when reaching adulthood. BDE-99 also induced adverse effects on learning and memory functions of mice. The estimated daily intake based on food consumption for PBDEs ranges from 44 to 51 ng/d, with fish contributing almost one-half. The BDE-99 body burden from a human milk survey can be estimated at 0.64 microg/kg, well below the experimental body burden of 0.4 mg/kg BDE-99 associated with behavioral alterations in neonatal mice. When considering the outlier value for PBDE-99 at 229 ng/g, this would result in an estimated PBDE-99 body burden of 46 microg/kg, or a MOS of only 9. However, no toxicokinetics data are available for humans, and the actual margin of safety may be much smaller if based on levels in critical target organs or tissues.

Toxicity of the chlordane metabolite oxychlordane in female rats: clinical and histopathological changes.

Due to widespread usage of the pesticide chlordane until the 1980's, this toxic and persistent mixture has accumulated in the food chain. The Arctic acts as a global sink for these and other persistent organic pollutants, which bioaccumulate in the marine and freshwater food chains. As a result, humans consuming diets high in Arctic fish and marine mammal fat can ingest higher levels of chlordane contaminants than humans consuming "southern" diets. The most abundant constituents of the chlordane mixture are trans-chlordane, cis-chlordane, trans-nonachlor, cis-nonachlor and heptachlor; oxychlordane is the major metabolite of the chlordanes and nonachlors. In humans the predominant chlordane-related contaminants detected in breast milk and adipose tissues are trans-nonachlor and oxychlordane. The present studies were undertaken to provide toxicological data on oxychlordane for the purpose of clarifying target organ toxicity and risks to human health associated with ingesting contaminated foods. Female rats were gavaged with oxychlordane at doses ranging from 0.01 to 10 mg/kg body weight/day for up to 28 days. In terms of general toxicity oxychlordane had a steep dose-response curve: 10 mg/kg oxychlordane was acutely toxic and 1 mg/kg oxychlordane caused no measurable effects. Weight loss, reduced feed consumption and thymic atrophy were the hallmarks of acute oxychlordane toxicity. At lower doses rats showed signs of hepatic changes indicative of microsomal enzyme induction. Oxychlordane was more bioaccumulative and was toxic at levels approximately 8 times lower than trans-nonachlor and cis-nonachlor. Thus, ingestion of trans-nonachlor and related chlordane contaminants in foods results in the formation of a metabolite that is more toxic and bioaccumulative than the parent contaminants.

Future human health research directions for the Canadian Northern Contaminants Program.

Studies conducted in the mid-1980s and early 1990s demonstrated that persistent organic pollutants (POPs) and metals were reaching the Arctic ecosystem at unexpectedly high levels, many of which had no Arctic or Canadian sources. Epidemiological and toxicological studies in Canada and in other countries have found that these contaminants may pose a risk to human health. The objective of this paper is to provide the foundation for the discussion on future northern human health research under the Northern Contaminants Program (NCP) in Canada. This short discussion of human health priorities will help guide a path forward for future northern human health research in Canada to address on-going and new health concerns related to contaminants exposure in the Canadian Arctic.

Melamine in infant formula sold in Canada: occurrence and risk assessment.

An analytical method incorporating simple liquid extraction followed by mixed mode cation exchange/reversed phase solid phase extraction and liquid chromatography-tandem mass spectrometry was developed and validated for the analysis of melamine (MEL) in liquid and powdered infant formula. The method used two different MEL stable isotope labeled internal standards to monitor analyte recoveries and to account for matrix effects. The method is sensitive (limit of quantitation of 4 ng/g), accurate, and precise (during validation, recoveries corrected by internal recovery standard averaged between 92 and 104% for all fortification levels and matrices). The method was used to analyze 94 samples of infant formula purchased from major retailers in Ottawa, ON, Canada, to examine whether or not Canadian infants are exposed to background levels of MEL. MEL was detected in 71 of the 94 products analyzed at concentrations ranging from 4.31 to 346 ng/g (median = 16 ng/g). A comparison of estimated dietary exposures to the recently recommended World Health Organization toxicological reference value for melamine suggests that the presence of low levels of MEL in infant formula purchased in Canada does not represent a health risk.

Reconstruction of methylmercury intakes in indigenous populations from biomarker data.

Significant amounts of methylmercury (MeHg) can bioaccumulate in fish and sea mammals. To monitor MeHg exposure in individuals, organic and inorganic mercury are often measured in blood samples or in hair strands, the latter being by far the best integrator of past exposure. With knowledge of the MeHg kinetics in humans, the levels of both biomarkers can be related to MeHg body burden and intakes. In the present study, we use the toxicokinetic model of Carrier et al. (2001) describing the distribution and excretion of MeHg in humans, to reconstruct the history of MeHg intakes of indigenous women of the Inuvik region in Canada starting from total mercury concentrations in hair segments. From these reconstructed MeHg intakes, the corresponding simulated mercury blood concentrations are found to be good predictors of the concentrations actually measured in blood samples. An important conclusion of this study is that, for almost all subjects, the reconstructed history of their MeHg intakes provides much lower intake values than intakes estimated from questionnaires on food consumption and estimated MeHg levels in these foods; the mean value of the reconstructed MeHg intakes is 0.03 microg/kg/day compared with the mean value of 0.20 microg/kg/day obtained from questionnaires. The model was also used to back-calculate the MeHg intakes from concentrations in hair strands collected from aboriginals of the Amazon region in Brazil, a population significantly more exposed than the population of the Inuvik region.