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KOLIANDRIS Damianos EHS 519

Introduction

Methyl mercury is ranked in the top ten groups of chemicals listed as environmental problem globally and is significant associated for public health issues^{8, 10}. Published literature suggests that methyl mercury is suspected to have negative effects brain development and the consumption of this compound pregnant woman may eventually lead significant neurological defects in newborns¹³.

We will identify the adverse effects (if any) of methyl mercury by examining major epidemiological and animal studies and using the mean levels of exposure, we will assess the level of exposure of methyl mercury and work out the BMDL and RfD.

Hazard Identification

We will study Mercury. Mercury exists in different forms, either in elements (or metals) as inorganic form (occupational exposure); and organic form such as methyl mercury (dietary exposure) ¹.

Mercury, a natural element in water, soil and air, is considered by WHO as one of the top 10 groups of chemicals of major public health concern^1. Methyl Mercury primarily targets the nervous system during its early development¹. That is why foetuses and young children are mostly vulnerable to Methyl Mercury’s adverse health effects. Methyl Mercury is oxidised in the brain and causes chronic diseases ^2,3,4,5.

Specifically, in the Faroe Islands, people consume whale meat at very high rates. The population was found to be highly contaminated and the researchers associated europsychological deficits at 7 years of age Developmental delays with the methylmercury exposures⁶.

The Faroe Islands and New Zealand studies provide evidence of a negative association between methylmercury in seafood consumed by pregnant women and the neurodevelopmental capabilities of the siblings at the age of 4 and 6-7 years old. Even in low concentrations of methylercury, the effects are small but still there ^6,8

The Seychelles study did not detect any significant associations between developmental tests and methylmercury exposure. The study measured concentration of hair mercury in pregnant mothers and then evaluated the development capabilities of children at 6.5, 19, 29 and 66 months of age⁷. From the study there is no evidence about the association of MeHg exposure and DDST-R where was showed in pilot study⁷.

The New Zealand study associated exposure to Methyl mercury with mental development of children at the age of 4 and 6-7 years old⁸. The study shoes a high exposure group consisted of 200 children (mean exposure = 9μg/g) at the age of 6 to 7 years old, lower mental capabilities were observed as opposed to the Control group with lower exposure rates. Nevertheless, JEFCA posed several methodological questions on this study^{1, 7}.

Exposure assessment

Various epidemiological studies were conducted in which researchers assed the level of exposure of the mothers of the children. Noteworthy attention is given in the study in the Faroe Islands⁶, in Seychelles⁷ and in New Zealand⁸.

The studies we examined ^6,7,8 and the report for WHO¹, suggest that the population is primarily exposed through seafood consumption. Since methylmercury oxidises in the brain during early development stages, the adverse effects are apparent to foetuses and young children where cognitive capabilities are mainly affected.

The population of Faroe Islands is not more than 50,000 people and the New Zealand is roughly 4.5 million. It is evident that population that resides in islands and fish consumption is highly observed, and then the exposure is of high rates. Typical levels of fish consumption vary between 1μg/g and 9μg/g (Faroe) and sometimes higher (10Μg/g in New Zealand).

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 estimation¹.

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 population in Faroe Islands was found to be highly contaminated of about 2 mg methyl mercury/kg⁶. The results were also (statistically) significant even when they excluded children whose mothers exceed 10 μg/g ⁶. This study included many neuropsychological tests such as Finger Tapping, Hand-Eye Coordination, an Intelligence scale (Wechsler), Similarities, and Block Designs, Visual and verbal tests by Bender⁶.

The 3 studies (Faroe, N. Zealand and Seychelles) were used by the US EPA to derive an RfD of 0.11 μg/Kg boy weight per day for methyl mercury. The benchmark dose was derived with an uncertainty factor of 10 and based on the 95% confidence levels of the 3 studies¹. The Joint FAO/WHO Expert Committee on Food Additives concluded pregnant women exposure to methyl mercury neurotoxic effects were the most sensitive health outcome of the 3 studies.

Original BMDLs of 17–24mg/kg were produced. Nevertheless, a single observation in the New Zealand study (86μg/Kg) seemed to inflate this BMDL, and when omitted a BMDLs of 7.4–10mg/kg was derived.

Minor adverse effects are expected when the threshold of 0.056μg/l is not exceed¹. This threshold was obtained 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:

[u1]

Using this equation, the Committee determined that a steady-state daily ingestion of methyl mercury 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 “inter individual variation in pharmacokinetics”

Risk Characterisation

Mercury, a natural element in water, soil and air, is considered by WHO as one of the top 10 groups of chemicals of major public health concern¹. Exposure to mercury – even small amounts – causes major health problems, and is treated for the development of the child in utero in early years. The studies have shown that people, who consume fish and shellfish, are more likely to be exposed to methylmercury¹.

References

1. WHO. (2006). Exposure to Mercury: A major public health concern. Preventing Disease Through Healthy Environments, 4. http://doi.org/10.1016/j.ecoenv.2011.12.007
2. Kanai, Y. et al (2003): Functional properties of multispecific amino acid transporters and their implications to transpoter-mediated toxicity. Journal of Toxicological Sciences. 28 (1): 1-17
3. Kerper et al (1992), Methylmercury transport across the blood-brain barrier by an amino acid carrier. American Journal of Physiology Regulatory Integrative and Comparative Physiology. 262 (5): 761-765.
4. Mottet et al, (1985), Health risks from increases in methylmercury exposure, , Environ Health Perspect. Nov;63:133-40.
5. Sakamoto et al (2004), Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption to fetus, Environ Sci Technol. Jul 15;38(14):3860-3.
6. Grandjean et al (1997), Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury, , Neurotoxicol Teratol. Nov-Dec;19(6):417-28.
7. 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.
8. Kjellstrom at al (1986), Physical and mental development of children with prenatal exposure to mercury from fish. Stage 2:Interviews and psychological tests at age 6. Report 3642, National Swedish Environmental Protection Board
9. Castoldi, A. F., Onishchenko, N., Johansson, C., Coccini, T., Roda, E., Vahter, M., … Manzo, L. (2008). Neurodevelopmental toxicity of methylmercury: Laboratory animal data and their contribution to human risk assessment. Regulatory Toxicology and Pharmacology, 51(2), 215–229. http://doi.org/10.1016/j.yrtph.2008.03.005
10. Stern, A. H., & Smith, A. E. (2003). An assessment of the cord blood: Maternal blood methylmercury ratio: Implications for risk assessment. Environmental Health Perspectives, 111(12), 1465–1470. http://doi.org/10.1289/ehp.6187
11. Gilbert, S. G., & Grant-Webster, K. S. (1995). Neurobehavioral effects of developmental methylmercury exposure. In Environmental Health Perspectives (Vol. 103, pp. 135–142). http://doi.org/10.1289/ehp.95103s6135
12. Grandjean, P., & Herz, K. T. (2011). Methylmercury and brain development: Imprecision and underestimation of developmental neurotoxicity in humans. Mount Sinai Journal of Medicine, 78(1), 107–118. http://doi.org/10.1002/msj.20228
13. UNEP DTIE Chemicals Branch, & WHO Department of Food Safety, Z. and F. D. (2008). GUIDANCE FOR IDENTIFYING POPULATIONS AT RISK FROM MERCURY EXPOSURE. Exposure.