Human biomonitoring of dioxins, furans, and non-ortho dioxin-like polychlorinated biphenyls (PCBs) in blood plasma from Old Crow, Yukon, Canada (2019).

Dioxins, furans, and dioxin-like polychlorinated biphenyls (PCBs) are a group of persistent and toxic chemicals that are known to have human health effects at low levels. These chemicals have been produced for commercial use (PCBs) or unintentionally as by-products of industry or natural processes (PCBs, dioxins, and furans). Additionally, dioxin-like PCBs were formerly used in electrical applications before being banned internationally (2004). These chemicals are widely dispersed in the environment as they can contaminate air and travel hundreds to thousands of kilometers before depositing on land or water, thereafter, potentially entering food chains. Community concerns surrounding the safety of traditional foods prompted a human biomonitoring project in Old Crow, Yukon Territory (YT), Canada (2019). Through collaborative community engagement, dioxins and like compounds were identified as a priority for exposure assessment from biobanked samples. In 2022, biobanked plasma samples (n = 54) collected in Old Crow were used to measure exposures to seven dioxins, ten furans, and four dioxin-like PCBs. 1,2,3,6,7,8-HxCDD, 1,2,3,7,8,9-HxCDD, 1,2,3,4,6,7,8-HpCDD, OCDD, 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF, PCB 126, and PCB 169 were detected in at least 50 % of samples. Among these analytes, the only congener at elevated levels was PCB 169, which was approximately ∼2-fold higher than the general population of Canada. No significant sex-based or body mass index (BMI) differences in biomarker concentrations were observed. Generally, the concentrations of the detected congeners increased with age, except for 1,2,3,4,6,7,8-HpCDD. For the first time, this research measures dioxin and like-compound exposures in Old Crow, advancing the information available on chemical exposures in the Arctic. Further research could be directed towards the investigation of PCB 169 exposure sources and temporal monitoring of exposures and determinants.

Dietary Intake Estimated From a 24-Hour Recall Questionnaire in the Dene and Métis Communities of the Northwest Territories, Canada.

Background: Food security and nutrient deficiencies are frequent issues for people living in northern remote regions of Canada. Objective: The objective of this study is to describe the nutrient intake of residents living in the Dene/Métis communities of the Dehcho and Sahtú regions of the Northwest Territories. Methods: A 24-h dietary recall survey was used to collect information from participants of a study completed in 9 communities during the winter seasons of January 2016 to March 2018. Intakes for food groups, vitamins, macroelements, and microelements were calculated. Nutrient intakes were compared with the available DRIs. Results: In total, there were 197 participants. On average, 37% of their energy was consumed from fat, and fruit/vegetable consumption was low (2.8 servings). Some vitamin levels (i.e., folate and vitamins A, B-6, C, and D) indicated a risk of nutritional deficiency for at least half of the participants. Of the nutrients examined, the nutrients least likely to meet the DRIs, according to the age/sex category of respondents were vitamin D (6%-20%), fiber (0%-11%), and calcium (4%-30%). Males tended to have a higher rate of nutrient adequacy above the DRIs. Importantly, 52% of the childbearing age female participants appeared deficient in folate, 48% deficient in zinc, 41% deficient in B12, and 22% deficient in iron, which might affect pregnancy and children's development. Conclusions: A focus on supporting a higher intake of nutrient-dense foods would benefit the health of these communities. Nutrition and health promotion programs should be implemented to improve public health efforts in the region.

Sources of exposure to lead in Arctic and subarctic regions: a scoping review.

Understanding lead exposure pathways is a priority because of its ubiquitous presence in the environment as well as the potential health risks. We aimed to identify potential lead sources and pathways of lead exposure, including long-range transport, and the magnitude of exposure in Arctic and subarctic communities. A scoping review strategy and screening approach was used to search literature from January 2000 to December 2020. A total of 228 academic and grey literature references were synthesised. The majority of these studies (54%) were from Canada. Indigenous people in Arctic and subarctic communities in Canada had higher levels of lead than the rest of Canada. The majority of studies in all Arctic countries reported at least some individuals above the level of concern. Lead levels were influenced by a number of factors including using lead ammunition to harvest traditional food and living in close proximity to mines. Lead levels in water, soil, and sediment were generally low. Literature showed the possibility of long-range transport via migratory birds. Household lead sources included lead-based paint, dust, or tap water. This literature review will help to inform management strategies for communities, researchers, and governments, with the aim of decreasing lead exposure in northern regions.

Dietary Intakes of Traditional Foods for Dene/Métis in the Dehcho and Sahtú Regions of the Northwest Territories.

A dietary transition away from traditional foods and toward a diet of the predominantly unhealthy market is a public health and sociocultural concern throughout Indigenous communities in Canada, including those in the sub-Arctic and remote regions of Dehcho and Sahtú of the Northwest Territories, Canada. The main aim of the present study is to describe dietary intakes for macronutrients and micronutrients in traditional and market food from the Mackenzie Valley study. We also show the trends of contributions and differences of dietary intakes over time from 1994 data collected and reported by the Centre for Indigenous People's Nutrition and Environment (CINE) in 1996. Based on 24-h dietary recall data, the study uses descriptive statistics to describe the observed dietary intake of the Dene First Nations communities in the Dehcho and Sahtú regions of the NWT. Indigenous people in Canada, like the sub-Arctic regions of Dehcho and Sahtú of the NWT, continue to consume traditional foods, although as a small percentage of their total dietary intake. The observed dietary intake calls for action to ensure that traditional food remains a staple as it is critical for the wellbeing of Dene in the Dehcho and Sahtú regions and across the territory.

Hair to blood mercury concentration ratios and a retrospective hair segmental mercury analysis in the Northwest Territories, Canada.

Concentrations of total mercury were measured in blood and hair samples collected as part of a human biomonitoring project conducted in First Nations communities of the Mackenzie Valley, Northwest Territories, Canada. Hair (n = 443) and blood (n = 276) samples were obtained from six communities in the Dehcho region and three communities in the Sahtú region of the Mackenzie Valley. The aim of this paper was to calculate hair to blood mercury ratios (for matched samples) and determine if: 1) ratios differed significantly between the two regions; 2) ratios differed from the 250:1 ratio proposed by the WHO; and, 3) point estimates of hair to blood mercury ratios could be used to estimate blood mercury concentrations. In addition, this paper aims to determine if there were seasonal patterns in hair mercury concentrations in these regions and if so, if patterns were related to among-season variability in fish consumption. The majority of mercury levels in hair and blood were below relevant health-based guidance values. The geometric mean hair (most recent segment) to blood mercury ratio (stratified by region) was 619:1 for the Dehcho region and 1220:1 for the Sahtú region. Mean log-transformed hair to blood mercury ratios were statistically significantly different between the two regions. Hair to blood ratios calculated in this study were far higher (2-5 times higher) than those typically reported in the literature and there was a large amount of inter-individual variation in calculated ratios (range: 114:1 to 4290:1). Using the 250:1 ratio derived by the World Health Organisation to estimate blood mercury concentrations from hair mercury concentrations would substantially over-estimate blood mercury concentrations in the studied regions. However, geometric mean site-specific hair to blood mercury ratios can provide estimates of measures of central tendency for blood mercury concentrations from hair mercury concentrations at a population level. Mercury concentrations were determined in segments of long hair samples to examine exposure of participants to mercury over the past year. Hair segments were assigned to six time periods and the highest hair mercury concentrations were generally observed in hair segments that aligned with September/October and November/December, whereas the lowest hair mercury concentrations were aligned with March/April and May/June. Mean log-transformed hair mercury concentrations were statistically significantly different between time periods. Between time periods (e.g., September/October vs. March/April), the geometric mean mercury concentration in hair differed by up to 0.22 µg/g, and the upper margins of mercury exposure (e.g., 95th percentile of hair mercury) varied by up to 0.86 µg/g. Results from self-reported fish consumption frequency questionnaires (subset of participants; n = 170) showed total fish intake peaked in late summer, decreased during the winter, and then increased during the spring. Visual assessment of results indicated that mean hair mercury concentrations followed this same seasonal pattern. Results from mixed effects models, however, indicated that variability in hair mercury concentrations among time periods was not best explained by total fish consumption frequency. Instead, seasonal trends in hair mercury concentrations may be more related to the consumption of specific fish species (rather than total wild-harvested fish in general). Future work should examine whether seasonal changes in the consumption of specific fish species are associated with seasonal changes in hair mercury concentrations.

Biomarkers of poly- and perfluoroalkyl substances (PFAS) in Sub-Arctic and Arctic communities in Canada.

Polyfluoroalkyl substances and perfluoroalkyl substances (PFAS) are a family of anthropogenic chemicals that are used in food packaging, waterproof clothing, and firefighting foams for their water and oil resistant properties. Though levels of some PFAS appear to be decreasing in Canada's south, environmental levels have been increasing in the Arctic due to long-range transport. However, the implications of this on human exposures in sub-Arctic and Arctic populations in Canada have yet to be established. To address this data gap, human biomonitoring research was completed in Old Crow, Yukon, and the Dehcho region, Northwest Territories. Blood samples were collected from adults residing in seven northern First Nations and were analyzed by liquid chromatography mass spectrometry. A total of nine PFAS were quantified: perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOS), perfluorohexane sulphonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA), perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulphonic acid (PFBS). In the Dehcho (n = 124), five PFAS had a detection rate greater than 50% including PFOS, PFOA, PFHxS, PFNA, and PFDA. In addition to these PFAS, PFUdA was also detected in at least half of the samples collected in Old Crow (n = 54). Generally, male participants had higher concentrations of PFAS compared to female participants, and PFAS concentrations tended to increase with age. For most PFAS, Old Crow and Dehcho levels were similar or lower to those measured in the general Canadian population (as measured through the Canadian Health Measures Survey or CHMS) and other First Nations populations in Canada (as measured through the First Nations Biomonitoring Initiative or FNBI). The key exception to this was for PFNA which, relative to the CHMS (0.51 µg/L), was approximately 1.8 times higher in Old Crow (0.94 µg/L) and 2.8 times higher in Dehcho (1.42 µg/L) than observed in the general Canadian population. This project provides baseline PFAS levels for participating communities, improving understanding of human exposures to PFAS in Canada. Future research should investigate site-specific PFNA exposure sources and monitor temporal trends in these regions.

Game bird consumption in Dene communities of the Northwest Territories, Canada.

OBJECTIVE: Game bird consumption is an important part of the diet of Indigenous populations in Canada and, as part of country food consumption, is associated with improved nutritional status. The objective of this project was to document the consumption of game birds for Dene First Nations in the Northwest Territories (NWT), Canada. DESIGN: Participants were invited to complete a FFQ using an iPad to document the types of country foods consumed, as well as consumption frequency and preparation methods, including thirteen types of game birds. SETTING: The project was implemented in nine communities in the Dehcho and Sahtú regions of the NWT, Canada. PARTICIPANTS: A total of 237 children and adult participants from Dene First Nations in the Mackenzie Valley region of the NWT took part in the current study. RESULTS: FFQ findings indicated that game birds were frequently consumed in both Dehcho and Sahtú communities. Canada goose and mallard were found to be consumed by the largest number of participants. Five different species (including Canada goose and mallard) were found to be consumed by at least 25 % of participants over the last year. When consuming game birds, most participants reported consuming the meat as well as most, if not all, other parts of the bird. CONCLUSIONS: Differences were observed since the last country food assessment in the 1990s in the same regions. These findings increase knowledge of the current Dene diet patterns and support the understanding of diet transition.

Human biomonitoring results of contaminant and nutrient biomarkers in Old Crow, Yukon, Canada.

Several large-scale human biomonitoring projects have been conducted in Canada, including the Canadian Health Measures Survey (CHMS) and the First Nations Biomonitoring Initiative (FNBI). However, neither of these studies included participants living in the Yukon. To address this data gap, a human biomonitoring project was implemented in Old Crow, a fly-in Gwich'in community in the northern Yukon. The results of this project provide baseline levels of contaminant and nutrient biomarkers from Old Crow in 2019. Samples of hair, blood, and/or urine were collected from approximately 44% of community residents (77 of 175 adults). These samples were analyzed for contaminants (including heavy metals and persistent organic pollutants (POPs)), and nutrients (including trace elements and omega-3 fatty acids). Levels of these analytes were compared to health-based guidance values, when available, and results from other human biomonitoring projects in Canada. Levels of lead (GM 0.64 µg/g creatinine in urine/24 µg/L blood), cadmium (GM 0.32 µg/g creatinine in urine/0.85 µg/L blood), and mercury (GM < LOD in urine/0.76 µg/L blood/0.31 µg/g hair) were below select health-based guidance values for more than 95% of participants. However, compared to the general Canadian population, elevated levels of some contaminants, including lead (approximately 2× higher), cobalt (approximately 1.5× higher), manganese (approximately 1.3× higher), and hexachlorobenzene (approximately 1.5× higher) were observed. In contrast, levels of other POPs, including insecticides such as dichlorodiphenyltrichloroethane (DDT), its metabolite, dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyls (PCBs) were similar to, or lower than, those reported in the general Canadian population. This study can be used along with future biomonitoring programs to evaluate the effectiveness of international initiatives designed to reduce the contaminant burden in the Arctic, including the Stockholm Convention and the Minamata Convention. Regionally, this project complements environmental monitoring being conducted in the region, informing local and regional traditional food consumption advisories.

Human biomonitoring of metals in sub-Arctic Dene communities of the Northwest Territories, Canada.

A human biomonitoring project investigating environmental exposures to metals from hair, blood and urine samples was implemented in the Northwest Territories, Canada, between January 2016 and March 2018. This study reports the metal biomarker levels from nine Dene communities located in the Dehcho and Sahtú regions to identify contaminants of interest. Levels of metals in the urine (n = 198), blood (n = 276) and hair (n = 443) samples were generally similar to those seen in other biomonitoring studies in Canada, but lead levels in blood (GM = 16 µg/L; 95th percentile = 71 µg/L) and urine (GM = 0.59 µg/L, 0.69 µg/g of creatinine; 95th percentile = 4.2 µg/L, 4.0 µg/g of creatinine) were higher than those observed in the Canadian Health Measure Survey (CHMS, cycles 2 and 5). Hair mercury (but not blood mercury) appeared higher than observed in participants from the CHMS cycle 5. The vast majority of participants had biomarker levels below the biomonitoring guidance values established for mercury and lead. Based on a comparative analysis of biomarker statistics relative to a nationally-representative survey, metals and essential trace elements of particular interest for follow-up research include: lead, manganese, mercury, and selenium. This project provided baseline biomarker levels in participating regions, which is essential to track changes in the future, and identify the contaminants to prioritize for further investigation of exposure determinants.

Food frequency questionnaire assessing traditional food consumption in Dene/Métis communities, Northwest Territories, Canada.

Food Frequency Questionnaires (FFQ) can be used to document food consumption and to estimate the intake of contaminants for Indigenous populations. The objective of this project was to refine and implement an FFQ to estimate the consumption of traditional locally harvested foods for Dene/Métis in the Northwest Territories, Canada. The strategy consisted of: 1) refining the FFQ through three focus groups and, 2) implementing the FFQ in Indigenous communities. Participants were asked to complete the FFQ using an iPad to document the types of traditional foods consumed over the past 12 months, as well as the consumption frequency, the portion size, and the preparation methods. Focus groups supported the refinement of the FFQ on the format, the list of foods, and the preparation methods listed in the questionnaire. The refined FFQ was then implemented with participants (n = 237). Findings indicated that the traditional foods most frequently consumed were moose, whitefish and lake trout. Participants who consumed fish and land animals reported, on average, a portion size for one serving of between 126 and 143 g, depending on age and sex. These findings increase knowledge of the current traditional food consumption of Dene/Métis communities and will support the assessment of contaminant exposure.

Polycyclic aromatic hydrocarbons (PAHs) levels in urine samples collected in a subarctic region of the Northwest Territories, Canada.

Traditional food consumption for Indigenous peoples is associated with improved nutrition and health but can also pose potential risks via exposure to contaminants. Polycyclic aromatic hydrocarbons (PAHs) are compounds of interest due to their widespread presence (e.g., their metabolites are detected in up to 100% of the Canadian population) and their toxicological potential. To better understand the range of exposures faced by Indigenous populations in northern Canada and to address a contaminant of emerging concern identified by the Arctic Monitoring and Assessment Programme, a multi-year biomonitoring study investigated levels of PAH exposure in subarctic First Nations communities of the Northwest Territories, Canada. Secondary data analysis of banked samples from a subset of the cross-sectional study was done. PAHs and cotinine markers in the urine samples (n = 97) of participants from two regions from the Mackenzie Valley (Dehcho and Sahtú) was completed by liquid and gas chromatography coupled with mass spectrometry. Also, participants completed a 24-hr recall food survey. When compared according to age/sex categories, the GM of several biomarkers (1-hydroxypyrene, 1-naphthol, 2-hydroxyfluorene, 2-hydroxyphenanthrene, 2-naphthol, 3-hydroxyfluorene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyfluorene, 9-hydroxyphenanthrene) appeared higher than observed for the general Canadian population. The PAHs levels observed were, however, below clinical levels associated with adverse health outcomes. Altogether, these elevated biomarkers are metabolites of pyrene, naphthalene, fluorene and phenanthrene. Statistically significant non-parametric associations were observed between several biomarkers and i) the consumption of cooked meat in the last 24 h; and, ii) smoking status (self-reported status and adjusted on urine cotinine level). This work is the first to report PAH levels in a northern Canadian population and provides local baseline data for monitoring the effects of changes to climate and lifestyle over time. These findings will support regional and territorial decision makers in identifying environmental health priorities.

Implementation of human biomonitoring in the Dehcho region of the Northwest Territories, Canada (2016-2017).

BACKGROUND: Human biomonitoring represents an important tool for health risk assessment, supporting the characterization of contaminant exposure and nutrient status. In communities where country foods (locally harvested foods: land animals, fish, birds, plants) are integrated in the daily diet, as is the case in remote northern regions where food security is a challenge, such foods can potentially be a significant route of contaminant exposure. To assess this issue, a biomonitoring project was implemented among Dene/Métis communities of the Dehcho region of the Northwest Territories, Canada. METHODS: Participants completed dietary surveys (i.e., a food frequency questionnaire and 24-h recall) to estimate food consumption patterns as well as a Health Messages Survey to evaluate the awareness and perception of contaminants and consumption notices. Biological sampling of hair, urine and blood was conducted. Toxic metals (e.g., mercury, lead, cadmium), essential metals (e.g., copper, nickel, zinc), fatty acids, and persistent organic pollutants (POPs) were measured in samples. RESULTS: The levels of contaminants in blood, hair and urine for the majority of participants were below the available guidance values for mercury, cadmium, lead and uranium. However, from the 279 participants, approximately 2% were invited to provide follow up samples, mainly for elevated mercury level. Also, at the population level, blood lead (GM: 11 µg/L) and blood cadmium (GM: 0.53 µg/L) were slightly above the Canadian Health Measures Survey data. Therefore, although country foods occasionally contain elevated levels of particular contaminants, human exposures to these metals remained similar to those seen in the Canadian general population. In addition, dietary data showed the importance and diversity of country foods across participating communities, with the consumption of an average of 5.1% of total calories from wild-harvested country foods. CONCLUSION: This project completed in the Mackenzie Valley of the Northwest Territories fills a data gap across other biomonitoring studies in Canada as it integrates community results, will support stakeholders in the development of public health strategies, and will inform environmental health issue prioritization.

Cadmium exposure in First Nations communities of the Northwest Territories, Canada: smoking is a greater contributor than consumption of cadmium-accumulating organ meats.

Traditional food consumption among northern populations is associated with improved nutrition but occasionally can also increase contaminant exposure. High levels of cadmium in the organs of moose from certain regions of the Northwest Territories, Canada, led to the release of consumption notices. These notices recommended that individuals limit their consumption of kidney and liver from moose harvested from the Southern Mackenzie Mountain. A human biomonitoring project was designed to better characterize exposure and risks from contaminants, including cadmium, among Dene/Métis communities of the Northwest Territories Mackenzie Valley, Canada. The project included a dietary assessment (food frequency questionnaire) to estimate moose and caribou organ (kidney and liver) consumption, as well as urine and blood sampling for the measurement of cadmium concentration using mass spectrometry. For a subset of the samples, urine cotinine was also quantified. The results from this biomonitoring research show that cadmium levels in urine (GM = 0.32 µg L-1) and blood (GM = 0.58 µg L-1) are similar to those observed in other populations in Canada. For the 38% of participants reporting eating game organs, current traditional food consumption patterns were not associated with cadmium biomarker levels. Instead, smoking appeared to be the main determinant of cadmium exposure. These results are supporting ongoing efforts at the community and territorial level to identify health priorities and design follow up plans in response to environmental monitoring data.

Design of a human biomonitoring community-based project in the Northwest Territories Mackenzie Valley, Canada, to investigate the links between nutrition, contaminants and country foods.

Community-based projects place emphasis on a collaborative approach and facilitate research among Indigenous populations regarding local issues and challenges, such as traditional foods consumption, climate change and health safety. Country foods (locally harvested fish, game birds, land animals and plants), which contribute to improved food security, can also be a primary route of contaminant exposure among populations in remote regions. A community-based project was launched in the Dehcho and Sahtù regions of the Northwest Territories (Canada) to: 1) assess contaminants exposure and nutrition status; 2) investigate the role of country food on nutrient and contaminant levels and 3) understand the determinants of message perception on this issue. Consultation with community members, leadership, local partners and researchers was essential to refine the design of the project and implement it in a culturally relevant way. This article details the design of a community-based biomonitoring study that investigates country food use, contaminant exposure and nutritional status in Canadian subarctic First Nations in the Dehcho and Sahtù regions. Results will support environmental health policies in the future for these communities. The project was designed to explore the risks and benefits of country foods and to inform the development of public health strategies.

Time courses and variability of pyrethroid biomarkers of exposure in a group of agricultural workers in Quebec, Canada.

PURPOSE: Cypermethrin is a pyrethroid pesticide widely used in agriculture. Exposure can be assessed through biomonitoring. However, interpretation of results requires a proper knowledge of the toxicokinetics of the exposure biomarkers of interest. This study aimed at characterizing typical urinary time courses of biomarkers of exposure to cypermethrin in farm workers in Quebec following an exposure episode, distribution of values and variability, and predictors of elevated excretion levels. METHODS: Workers provided total voids before seasonal spraying and during three consecutive days following an exposure period. Personal factors, professional tasks, and exposure conditions were documented by questionnaire. The urinary metabolites cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (DCCA) and 3-phenoxybenzoic acid (3-PBA) were quantified. RESULTS: Time courses showed significant variations of metabolite levels through time, although a clear profile typical of an acute exposure episode was not observed for several workers. However, maximum urinary levels in most exposed workers were generally reached 18-32 h following the onset of an exposure episode. Group comparison showed that applicators had higher excretions than workers performing inspection, harvest, or weeding. CONCLUSIONS: Time-dependent variations in excretions indicate the importance of serial urinary collections for a proper interpretation of a worker exposure pattern. In the context of group comparison, the alternative based on observed time courses and peak levels in most exposed workers would be the collection of urine samples prior to an exposure episode, at the end-of-shift after exposure onset and following morning void. When spot samples can only be collected for population exposure assessment, Monte Carlo simulations showed that iterative random selection of single urinary values from individual time courses observed in this study to predict distribution of values in the group of workers converged to similar central tendencies.

Detailed Urinary Excretion Time Courses of Biomarkers of Exposure to Permethrin and Estimated Exposure in Workers of a Corn Production Farm in Quebec, Canada.

Permethrin is a synthetic pyrethroid insecticide widely used in agriculture. Farm workers are thus regularly exposed during spraying season. To help interpret routine biomonitoring results, a proper knowledge of the time courses of biomarkers of exposure is necessary. The kinetics of biomarkers of exposure to permethrin has recently been documented in volunteers exposed to permethrin under controlled conditions but there is a lack of detailed time profiles following real exposure conditions. This study aimed at obtaining data on the excretion time courses of permethrin metabolites in agricultural workers following typical exposure conditions in the field. Twelve workers exposed to permethrin were recruited from a corn production farm in the Montérégie, Quebec, Canada. They provided all their urine voided over a period of 3 days following the onset of a spraying episode of permethrin or work in a treated area. Three major metabolites of permethrin, trans- and cis- 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-l-carboxylic acid metabolites (trans-DCCA, cis-DCCA), and 3-phenoxybenzoic acid (3-PBA), were analyzed. For the applicator, a progressive rise in excretion values was observed with a single peak being reached 29h following the onset of the 3.5h exposure and ensuing elimination with a half-life of 6.4h for trans-DCCA and 8.7h for 3-PBA. In the other workers (supervisor and corn pickers), excretion profiles were generally more compatible with multiple entries in the treated area during the 3-day sampling period and rapid elimination between exposure episodes. In general, 3-PBA was found in slightly higher levels than trans-DCCA, except for the applicator and a harvester. For both trans-DCCA and 3-PBA in a given worker, excretion values expressed as creatinine-normalized concentrations were less variable than those expressed as excretion rates per kilogram body weight. Time-dependent variability in excretion values of workers confirms the need for serial urine sampling of at least two biomarkers of exposure, with minimally pre-exposure, end-of-shift sample the day of onset of exposure, and following morning void.

Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.

Biomonitoring of pyrethroid exposure is largely conducted but human toxicokinetics has not been fully documented. This is essential for a proper interpretation of biomonitoring data. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers have been documented and compared with previously available kinetic data following permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of cypermethrin acutely. The same volunteers were exposed to permethrin earlier. Blood samples were taken over 72 h after treatment and complete timed urine voids were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3-phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and permethrin, were quantified. Blood and urinary time courses of all three metabolites were similar following cypermethrin and permethrin exposure. Plasma levels of metabolites reached peak values on average ≈ 5-7 h post-dosing; the elimination phase showed mean apparent half-lives (t½ ) for trans-DCCA, cis-DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing. Corresponding mean values obtained from urinary rate time courses were peak values at ≈ 9 h post-dosing and apparent elimination t½ of 6.3, 6.4 and 6.4 h for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data confirm that the kinetics of cypermethrin is similar to that of permethrin in humans and that their common biomarkers of exposure may be used for an overall assessment of exposure.

Toxicokinetics of permethrin biomarkers of exposure in orally exposed volunteers.

Permethrin is a widely used pyrethroid insecticide for which the toxicokinetics of exposure biomarkers in humans is not fully documented. The time courses of key biomarkers of permethrin exposure were thus assessed in accessible biological matrices of orally exposed volunteers. Six volunteers ingested 0.1 mg/kg body weight of permethrin (60:40 trans/cis). Blood samples were withdrawn at fixed periods over 72 h following ingestion and complete timed-urine voids were collected over 84 h post-dosing. Cis-and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acids (cis-and trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were quantified in samples. In plasma, peak concentrations of cis-DCCA, trans-DCCA and 3-PBA were reached about ≈7 h post-dosing, and elimination appeared monophasic with a mean apparent elimination half-life (t½) of 6.2, 7.1 and 6.5 h, respectively. In urine, elimination rate time courses of cis-DCCA, trans-DCCA and 3-PBA evolved in parallel with plasma, with respective mean apparent elimination t½ of 4.5, 5.4 and 5.7 h. Over the 84 h period post-treatment, 43-46% of administered molar dose were excreted in urine as trans-DCCA (molar % of trans-permethrin) and 3-PBA. Results show similarities in the different metabolite profiles and a rapid equilibrium between urine and plasma levels; data should help interpret the significance of biological measurements and optimal sampling strategies.