home edit2 whole TSD November 2002 PDF format - OEHHA

propylamine in drinking water at 0.9 mg/day for 5 days/week for 30 weeks resulting in a daily dose of
2.6 mg/kg-day. No control group was included. Esophageal carcinomas (20/20) and forestomach
tumors (12/20) developed in exposed animals.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
US EPA (1986) based its selection of a cancer potency on a study which demonstrates induction of
liver tumors by N-nitrosodi-n-propylamine. US EPA (1986) used the data from Druckrey et al.(1967)
in the induction of hepatocellular carcinoma in BD rats exposed to N-nitrosodi-n-propylamine in
drinking water to calculate a cancer potency value.
Methodology
The high tumor incidence in all the N-nitrosodi-n-propylamine treated animals suggests time-dependent
analysis is more appropriate than multistage analysis in the derivation of a cancer potency value. A
dosage estimate for use in deriving the cancer potency value was based on the following relationship,
where d is the daily dose, C is the mmol to mg conversion factor (130.2 mg/mmol), k is an empirically
derived constant estimated from a plot of k versus the number of carbon atoms for lower di-Nalkylnitrosamines
(k=1.7 × 10 4 mmol/kg-day), t 50 is the median time of tumor induction, and n is a
representative value for dialkylnitrosamines (n=2.3; Druckrey et al., 1967):
d = C × k
The resulting daily dose estimate was 0.578 mg/kg-day. Applying this estimate to a rearrangement of
the one-hit model gave an animal cancer potency value (q animal ) of 1.2 (mg/kg-day) -1 .
q animal = -ln(0.5/day) / d
Conversion of the q animal to a human cancer potency estimate (q human ) was made based on the following
relationship, where bw h is the assumed human body weight (70 kg) and bw a is the assumed
experimental animal body weight (0.35 kg):
t 50
n
q human = q animal × (bw h /bw a ) 1/3
The resulting estimate of q human was 7.0 (mg/kg-day) -1 .
A unit risk value based upon air concentrations was derived by OEHHA/ATES using an assumed
human breathing rate of 20 m 3 /day, 70 kg human body weight, and 100% fractional absorption after
inhalation exposure. The calculated unit risk value is 2.0 E-3 (µg/m 3 ) -1 .
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