home edit2 whole TSD November 2002 PDF format - OEHHA

ationale for selection of the OEHHA unit risk value for NDMA.
Methodologies
Peto et al .(1982, 1984) derived potency values from the incidence data of fatal liver tumors in male
and female Colworth rats. The cumulative risk was calculated based on the assumption that the risk
increases with the seventh power of exposure duration and the observation that a dose of 1.0 µg/kgday
results in a 0.03-0.04% incidence of liver tumors at two years. Estimated cancer potency at low
doses (q animal ) was found to be 0.29 and 0.4 (mg/kg-day) -1 for male and female rats, respectively. Peto
et al. (1982,1984) also scaled these potencies up by a factor of 7 to account for calculated increased
risk from the observation that median experimental animal lifespan was beyond 2 years in this study.
Conversion to human potency values (q human ) was based on the body weight scaling relationship
described below, with an assumed human body weight (bw h ) of 70 kg and experimental animal body
weights (bw a ) of 450 and 250 g for male and female rats:
q human = q animal × (bw h /bw a ) 1/3
The resulting q human values were 12 and 16 (mg/kg-day) -1
respectively.
from the male and female rat data,
Dose rate estimates of 0.82 mg/kg-day for female BALB/c mice receiving NDMA in drinking water in
the study by Terracini et al. (1973) were based on a US EPA (1988) reference animal body weight
value and water consumption rate (CDHS, 1988). Using a multistage procedure, experimental
potencies (q 1 * ) derived from this dose rate using the incidence of lung tumors in F 0 and F 1 generation
animals were 1.5 and 1.6 (mg/kg-day) -1 , respectively. Potency in animals (q animal ) was estimated
assuming cancer incidence increases with the third power of age, with T e the experimental duration and
T the natural lifespan of the animals (104 weeks):
q animal = q 1 * × (T/T e ) 3
Further conversion to human cancer potencies with a body weight scaling factor were made as
described for Peto et al.(1982,1984) resulting in human potency estimates (q human ) of 49 and 53
(mg/kg-day) -1 from the F 0 and F 1 generation mouse tumor incidence data, respectively.
High- and low-dose rates estimates of 0.80 and 0.35 mg/kg-day in the study by Lijinsky and Reuber
(1984) were based on US EPA (1988) animal body weight reference values in the induction of liver
tumors in Fischer 344 rats (CDHS, 1988). Using the Crouch (1983) correction for variable dosing and
a multistage procedure, the animal cancer potency estimate (q animal ) was 5.8 (mg/kg-day) -1 . Using the
body weight conversion factor as described in the Peto et al. (1982, 1984) potency derivation
(bw a =0.229 kg; US EPA, 1988), the resulting q human was 39 (mg/kg-day) -1 .
Dose rate estimates to MRC Porton rats exposed to NDMA in diet in the study by Terracini et al.
(1967) were made by the method of Crouch (1983) to account for variable dosing during the course of
the experiment (CDHS, 1988). Using liver tumor incidence among female rats surviving less than 60
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