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

MERCURY A-24
APPENDIX A
pharmacokinetic variability on the relationship between ingestion rate and hair concentration for methylmercury.
The resulting distribution had a geometric mean value of 0.00160 mg/kg/day (S.D. 0.00133). The
1st, 5th, and 10th percentiles of that distribution were 0.00086, 0.00104, and 0.00115 mg/kg/day,
respectively. Clewell et al. (1998) suggested that the 5th percentile of 0.00104 mg/kg/day provides a
scientifically based, conservative basis that incorporates the pharmacokinetic variability across the U.S.
population of child-bearing women and that no other uncertainty factor for interindividual variability would
be needed. To the benchmark-estimated NOAEL of 21 ppm derived from the Seychelles 29-month data,
Clewell et al. (1998) applied an uncertainty factor of 3 to account for data base limitations. (Note: The
66-month Seychelles data was not yet published at the time; hence the reliance on the 29-month Seychelles
data for the benchmark analysis.) Consequently, Clewell et al. (1998) concluded that using a NOAEL of
7 ppm (21 ppm / 3 (UF) provides additional protection against the possibility that effects could occur at
lower concentrations in some populations. Based upon this reasoning, they recommended a health guidance
value (i.e., an RfD) of 0.0004 mg/kg/day. If a modifying factor of 1.5 is used to further address the domainspecific
findings in the Faroe study, a final MRL of 0.3 µg/kg/day results.
The above benchmark analysis of 29-month data from the Seychelles Child Development Study strongly
supports the MRL of 0.0003 mg/kg/day calculated by ATSDR in this profile. Similarly, addressing the
Seychellois 66-month data from the perspective of using the mean value (15.3 ppm) of the highest exposure
group in the study, a method prescribed in ATSDR's published guidance for MRL development (Chou et al.
1998), also results in an identical MRL. ATSDR therefore has high confidence that this level is protective of
the health of all potentially exposed human populations.
Agency Contact (Chemical Manager): John F. Risher