revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 256
2. HEALTH EFFECTS
domain-specific neuropsychological test results from the Seychelles are not yet available. When these results
become available and if they fail to show domain-specific effects, this additional factor of 1.5 would no
longer be needed. At that time ATSDR will re-evaluate its MRL, as well as all other relevant data, in
compliance with the agency’s mandates and authorities.
Therefore, in the calculation of the chronic oral MRL for methylmercury, the NOAEL of 0.0013 mg/kg/day
from the 66-month study (Davidson et al. 1998) is divided by 4.5, giving a chronic oral MRL for
methylmercury of 0.0003 mg/kg/day [0.0013 mg/kg/day / 4.5 (UF) = 0.0003 mg/kg/day].
Alternative Derivations of the MRL
To ensure a health guidance value based upon the best use of the Seychelles study data (widely considered the
most relevant data available), ATSDR evaluated alternate MRL derivation methods for methylmercury. One
such approach is to use the mean total mercury level of 6.8 ppm in maternal hair for the entire Seychellois
study cohort. Using the same formula as in the previous MRL calculation,
C = (0.95 x 0.05 x d) / (0.014 x 4.2)
C = 0.81 d
(1/250 x 6.8) = 0.027
0.027 mg/L = 0.81 d
d = 0.034 mg/day
0.034 mg/day / 60 kg = 0.0006 mg/kg/day
In consideration of uncertainty factors for this MRL approach, multiple factors also apply. In this case, the
mean value of 6.8 ppm for the NOAEL is for the entire study cohort at 66 months (n = 711). An uncertainty
factor of 1.5 was used to account for the pharmacokinetically based variability of hair-to-blood ratios (95%
confidence level) in pregnant women and fetuses in the U.S. population (Clewell et al. 1998, 1999). The
extremely large size of the study population (n=711), in combination with an uncertainty factor of 1.5, is
considered adequate to encompass the full range of pharmacokinetic and pharmacodynamic variability
within the human population. An independent modifying factor of 1.5 was also used to take into
consideration the positive results of the domain-specific tests administered in the Faroe study (Grandjean
et al. 1997, 1998). The uncertainty factor of 1.5, multiplied by the modifying factor of 1.5, yields a total
aggregate value of 2.25. Applying the factor of 2.25 to the daily intake calculated from the 6.8 ppm