Doses Associated with the EPA RfC and the ATSDR MRL versus FDA’s

A. Internal doses associated with the RfC and MRL

The FDA attempts to convert the RfC and MRL to an absorbed dose in their Final Rule, incorrectly estimating the following internal doses:

Age group

RfC-associated intake (μgs/day)

MRL-associated intake (μgs/day)


4.9 3.2

5 year old Children

2.3 1.5

1 year old Infants

1.7 1.2


However, in calculating these absorbed doses, the FDA makes four key errors.

  1. it uses unreliable values for inhalation rates;
  2. it fails to adjust the inhaled doses for the 80% absorption of mercury vapor in the lungs, an absorption rate acknowledged elsewhere in FDA’s Final Rule
  3. it fails to standardize the internal doses associated with the RfC and MRL (and those from amalgam) with various body weights to account for the great weight disparities found in the different age groups under consideration.
  4. the RfC-associated dose and MRL-associated dose is derived for adults only, theage group studied in the occupational studies upon which the RfC and MRL are based

B. Inhalation and Absorption Rates

Rather than accessing the most nationally and internationally authoritative data and information on inhalation rate – that compiled and thoroughly analyzed by the US EPA (1997;2008) — the FDA chose to estimate inhalation rates on the basis of only two citations. USEPA’s Exposure Factors Handbook (EPA 1997) reviews twenty-one key and dependable studiesto determine that the adult inhalation rate is 13.25 m3/day for males and females combined. This is significantly less than FDA’s undependable estimate of 16.2 m3/day.

The FDA acknowledges on page 8 of its Final Rule that the inhaled absorption rate for mercury vapor is 80%, yet it fails to apply this factor to its calculations in deriving the absorbed doses based on the RfC and MRL. Instead, FDA assumes 100% absorption of the inhaled mercury vapor. This error incorrectly pushes the permissible dose higher than is should be.

C. Standardization to Account for Varying Body Weights

In order to conduct any form of comparison of the FDA’s assumed mercury vapor dose(1 to 5 μgs per seven to ten fillings) to the EPA RfC or ATSDR MRL (0.3 μg/m3 and 0.2 μg/m3, respectively) it is necessary to convert both the exposure estimate and the reference exposure levels to the same units. To do this, both must be converted to absorbed, weight-standardized doses in units of μgs/kg body weight/day.

The internal dose associated with the EPA RfC for mercury vapor (0.3 μgs/m3) can be determined by consideration of inhalation rate and body weight in adults, the population group investigated in the occupational epidemiology study upon which the RfC was based, and adjustingfor 80% absorption. According to the US EPA, adult average inhalation rate is 13.25 m3/day(EPA, 1997; average of males and females) and average adult body weight is 71.8 kg (EPA 1997;average of males and females). Assuming that 80% of inhaled mercury vapor is absorbed (asassumed by the FDA in their Final Rule), the internal RfC-associated reference dose is: (0.3μgs/m3 x 13.25 m3/day X 80%)/71.8 kg = 0.044 μgs/kg body weight/day. For the MRL of 0.2μg/m3, the equivalent internal MRL-associated reference dose is similarly derived as 0.03 μg/kgbw/day.

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