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

MERCURY 230
2. HEALTH EFFECTS
the MRL; that is, the relationship between inhaled concentration and target tissue concentration at the
LOAEL and at lower levels (including the MRL) did not differ. Therefore, exposure concentrations were
used directly for the analysis. Gentry et al. (1998) also assumed that 1% of the unexposed population
would be considered in the adverse response range. The BMD 10 was the dose at which the probability of
exceeding the 1% adverse response level was 10% greater than in unexposed individuals, and the BMDL 10
is the 95% lower bound confidence level on that dose. A simple linear model sufficed to describe the dose-
response. A BMDL 10 of 0.017 mg metallic mercury/m 3 was derived as a reasonable representation of the
sparse data. This level would be equivalent to a NOAEL (i.e., no LOAEL to NOAEL uncertainty factor is
needed). Using a PBPK model to estimate target tissue doses from inhaled mercury vapor and adjusting for
continuous exposure and interhuman variability (with an uncertainty factor of 10), an MRL of
0.0004 mg/m 3 (based on target tissue dose) was derived which is about two times the ATSDR derived MRL
of 0.0002 mg/m3 based upon the Fawer et al. (1983) LOAEL.
The ability of long-term, low-level exposure to metallic mercury to produce a degradation in neurological
performance was also demonstrated in other studies. One such study (Ngim et al. 1992) attributed adverse
neurological effects to a lower average level of exposure than did the Fawer et al. (1983) study; however,
this study was not used in deriving a chronic inhalation MRL due to uncertainties concerning the study
protocol, including methodological and reporting deficiencies. In the Ngim et al. (1992) study, dentists
with an average of 5.5 years of exposure to low levels of metallic mercury were reported to have impaired
performance on several neurobehavioral tests. Exposure levels measured at the time of the study ranged
from 0.0007 to 0.042 mg/m 3 , with an average of 0.014 mg/m3 . Mean blood mercury levels among the
dentists ranged from 0.6 to 57 µg/L, with a geometric mean of 9.8 µg/L. The performance of the dentists
on finger tapping (measures digital motor speed), trail-making (measures visual scanning and motor speed),
digit symbol (measures visuomotor coordination and concentration), digit span, logical memory delayed
recall (measure of verbal memory), and Bender-Gestalt time (measures visual construction) tests was
significantly poorer than controls. The exposed dentists also showed higher aggression than did controls.
Furthermore, within the group of exposed dentists, significant differences were observed between a
subgroup with high mercury exposure compared to a subgroup with lower exposure. These exposure
severity subgroups were not compared to controls, and average exposure levels for the subgroups were not
reported. The design and reporting of this study limits its usefulness in deriving an MRL for metallic
mercury. The exposure status of the subjects was known to the investigator during testing, mercury levels
were not reported for controls, and methods used to adjust for potential contributions other than mercury
from amalgams to the study results (such as the possible use in this population of traditional medicines