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Risks and Hazards Related to Mercury Handling and Manufacture
Mercury
Mercury exists in various forms: elemental (or metallic) and inorganic (to which people may be exposed through their occupation); and organic (e.g., methylmercury, to which people may be exposed through their diet). Mercury occurs naturally in the earth's crust.
Key facts[1]
- Mercury is a naturally occurring element that is found in air, water and soil.
- Exposure to mercury – even small amounts – may cause serious health problems, and is a threat to the development of the child in utero and early in life.
- Mercury may have toxic effects on the nervous, digestive and immune systems, and on lungs, kidneys, skin and eyes.
- Mercury is considered by WHO as one of the top ten chemicals or groups of chemicals of major public health concern.
- People are mainly exposed to methylmercury, an organic compound, when they eat fish and shellfish that contain the compound.
Hazard Identification
Methylmercury can enter the brain where it is oxidized and accumulated and eventually causes chronic exposure and, depending on the level of exposure, can lead to adverse human health effects (Sakamoto et al, 2004). The critical target for methylmercury toxicity is the nervous system, especially during its developmental stage.
Three epidemiological studies that have received significant attention are studies in the Faroe Islands (Grandjean, 1997), Seychelles (Myers, 1997) and New Zealand (Kjellstrom, 1982). The measure of exposure in these studies was hair mercury of the mothers of the children in the study.
The Faroe Islands population was exposed to methylmercury largely from contaminated pilot whalemeat, which contained very high levels of about 2 mg methylmercury/kg. The study of about 900 Faroese children showed that prenatal exposure to methylmercury resulted in europsychological deficits at 7 years of age Developmental delays were significantly associated with the methylmercury exposures, even excluding the children whose mothers had higher hair mercury levels (above 10 μg/g). These associations remained after adjustment for covariates and after exclusion of children with maternal hair mercury concentrations above 10 microgram(s) (50 nmol/g). Neuropsychological tests included Finger Tapping; Hand-Eye Coordination; reaction time on a Continuous Performance Test; Wechsler Intelligence Scale for Children-Revised Digit Spans, Similarities, and Block Designs; Bender Visual Motor Gestalt Test; Boston Naming Test; and California Verbal Learning Test (Children). (Grandjean et al., 1997).
The Seychelles Child Development Study analyzed developmental milestones similar to those determined in Iraq in a large controlled, prospective study of children exposed prenatally to methylmercury when their mothers ate fish. As part of this ongoing study, cohort children were evaluated at 6.5, 19, 29, and 66 months of age. At 19 months care-givers were asked at what age the child walked (n=720 out of 738) and talked (n=680). No effects on developmental tests up to 5.5 years of age were found to be associated with methylmercury exposure, as measured by hair mercury concentrations in the pregnant mothers.
The study from New Zealand suggests an effect on the mental development of children at the age of 4 and 6-7 years. In a high-exposure group, the average maternal hair mercury concentration was about 9 μg/g; control groups were selected with lower exposure levels. About 200 children were examined at 6-7 years of age, and a negative association was found between maternal hair mercury concentrations and neuropsychological development of the children. Methodological questions surrounding this study were posed by JEFCA.
Exposure assessment
The entire population is exposed mainly through seafood consumption. The negative effect concerns mainly foetuses and young children as far as their mental development is concerned. The Faroe Islands and New Zealand studies have recently provided evidence that methylmercury in seafood consumed by pregnant women—even at low mercury concentrations (about 10–20 % of observed effect levels on adults)—appears to have subtle, persistent effects on children’s mental development as observed at about age 4 to 7 (so-called cognitive deficits) (Grandjean, 1997; Kjellstrom, 1986). The measure of exposure in these studies was hair mercury of the mothers of the children in the study.
The New Zealand study suggests an effect on the mental development of children at the age of 4 and 6-7 years. In a high-exposure group, the average maternal hair mercury concentration was about 9 μg/g; control groups were selected with lower exposure levels.
The Joint FAO/WHO Expert Committee on Food Additives (JECFA determined that a steady-state daily ingestion of methylmercury of 1.5 μg/kg body weight/day would result in the concentration in maternal blood estimated to be without appreciable adverse effects in the offspring in the Faroe and Seychelles Islands studies.
Country/Organization |
Reference Level (μg MeHg/kg bw/ week) |
Year adopted |
Canada |
1.4 |
1997 |
Japan |
2 |
2005 |
Netherlands |
0.7 |
2000 |
USA |
0.7 |
2001 |
JECFA |
1.6 |
2003 |
Table 1: GUIDANCE FOR IDENTIFYING POPULATIONS AT RISK FROM MERCURY EXPOSURE, August 2008, Issued by UNEP DTIE Chemicals Branch and WHO Department of Food Safety, Zoonoses and Foodborne Diseases
Dose-Response Analysis
The US EPA developed an RfD of 0.1 µg/kg body weight per day for methylmercury. The current RfD was derived from a benchmark dose (BMD) divided by an uncertainty factor of 10. The BMD analysis used was based on the lower 95 % confidence limit for a 5 % effect level, from several endpoints in the Faroe, New Zealand and Seychelles studies.
The JECFA[2] concluded that neurotoxic effects resulting from exposure to methylmercury in utero were the most sensitive health outcome. A number of dose–response assessments have been conducted using the results of the three major epidemiological studies of fetal neurotoxicity, conducted in the Faroes Islands, the Seychelles, and New Zealand. These assessments were made on the basis of evaluations of children at 7 years of age in the Faroes Islands study, 5.5 years of age in the Seychelles Islands study, and 6 years of age in the New Zealand study. Mercury in maternal hair and/or cord blood served as the primary biomarkers of exposure to methylmercury in utero in the studies in the Faroe Islands and the Seychelles.
The maternal hair-mercury concentration corresponding to a NOEL for neurobehavioural effects was identified for the study in the Seychelles, and a mathematical analysis of the concentration– response relationship was used to determine a benchmark-dose lower-confidence limit (BMDL) for the studies in the Faroes Islands and New Zealand.
JECFA noted that the maternal hairmercury concentration of one child (out of 237) in the study in New Zealand was 86 mg/kg, more than four times the next highest concentration in the study sample and had a heavy impact on the BMDLs.
The inclusion of this observation produced BMDLs of 17–24mg/kg, while omitting it produced BMDLs of 7.4–10mg/kg. Because of uncertainty about which set of BMDLs was most valid, the
Calculation of steady-state ingestion of methylmercury (mg/kg of body weight per day) from a maternal hair-mercury concentration comprises two steps: conversion of the concentration of methylmercury in maternal hair to that in maternal blood, and conversion of the concentration of mercury in maternal blood into maternal intake.
The mean ratio of the concentrations of methylmercury in hair to those in blood was determined in a number of studies, using samples from various study groups and with a variety of analytical methods, and was usually in the range of 140–370.
The concentration of methylmercury in maternal blood that would be expected to have no appreciable adverse effects on the offspring was calculated to be 0.056 mg/l, determined by dividing a maternal hair-mercury concentration of 14mg/kg by the hair: blood ratio of 250. In humans, the steady state concentration of mercury in blood can be related to average daily intake using a one-compartment model that incorporates refinements to the original WHO formula, as follows:
Using this equation, the Committee determined that a steady-state daily ingestion of methylmercury at 1.5 mg/kg of body weight per day would result in a maternal blood-mercury concentration that would have no appreciable adverse effects on offspring in these two study populations.
Potential human variability was taken into account by the application of adjustment or uncertainty factors such as “interindividual variation in pharmacokinetics”
Risk Characterisation
Validates the mercury exposure biomarkers
Grandjean, P., Jørgensen, P.J., Weihe, P. (2002): Validity of mercury exposure biomarkers. In: Wilson SH, Suk WA, Eds. Biomarkers of Environmentally Associated Disease. Boca Raton, FL, CRC Press/Lewis Publishers, pp. 235-247.
References
- Grandjean, P., Weihe, P., White, R. F., Debes, F., Araki, S., Yokoyama, K., … JØrgensen, P. J. (1997). Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicology and Teratology, 19(6), 417–428.
- Mitchell, J. W., Kjellstrom, T. E., & Reeves, R. L. (1982). Mercury in takeaway fish in New Zealand. New Zealand Medical Journal, 95(702), 112–114.
- Mottet, N. K., Shaw, C. M., & Burbacher, T. M. (1985). Health risks from increases in methylmercury exposure. Environmental Health Perspectives.
- Myers, G. J., Davidson, P. W., Shamlaye, C. F., Axtell, C. D., Cernichiari, E., Choisy, O., … Clarkson, T. W. (1997). Effects of prenatal methylmercury exposure from a high fish diet on developmental milestones in the Seychelles Child Development Study. Neurotoxicology, 18(3), 819–829.
- Sakamoto, M., Kubota, M., Liu, X. J., Murata, K., Nakai, K., & Satoh, H. (2004). Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption to fetus. Environmental Science & Technology, 38(14), 3860–3863.
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[1] http://www.who.int/mediacentre/factsheets/fs361/en/
[2] Joint FAO/WHO Expert Committee on Food Additives
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