home edit2 whole TSD November 2002 PDF format - OEHHA

US EPA (1986,1987, 1988) based estimates of cancer potency on the following relationship where p(t)
is the probability of developing a tumor in a study of cohort of average age t at the end of the follow-up
period (56.5 years) and an average lifespan t L (71.3 years), exposed to dose level d (0.0063 mg/kgday),
and assuming that background tumor incidence is negligible:
cancer potency =
-ln (1- p(t))
(d)( t
t L
) 3
With this model, US EPA used total tumor incidence (13/25, both benign and malignant) in its
calculation, giving a final potency value of 234 (mg/kg-day) -1 (See Table 2). Using the upper 95%
confidence bound on the tumor incidence (0.68 vs. 0.52) resulted in a cancer potency value of 363
(mg/kg-day) -1 .
Using mean urine benzidine concentrations reported at the beginning (0.01 mg/l) and end (0.04 mg/l) of
the work day, Allen et al. (1987) adjusted benzidine exposure estimates on the assumption of linear
increases in urine concentration during the workday and first-order decay during non-work hours. The
resulting average urine concentration during workdays was 0.023 mg/l. Based on assumptions that
1.5% of the inhaled benzidine is present in the urine (100% absorption), urinary output is 1.5 l/day,
breathing rate is 10 m 3 /8-hour work day, and average exposure time of the cohort is 11.24 years, Allen
et al. (1987) estimated average cumulative dose to be 2.59 mg-yrs/m 3 .
Allen et al. (1987) calculated potency using this dose value and the malignant tumor incidence only [p(t)
= 11/25 = 0.44] with a background tumor incidence factor (α = 0.002; NIH, 1981) and without using
a time adjustment factor. That is:
cancer potency =
-ln [1- p(t )] +
d
α
The resulting estimate of cancer potency from work place exposure was 0.22 (mg⋅yrs/m 3 ) -1 . with
upper and lower 90% confidence bounds of 0.81 and 0.045 (mg⋅yrs/m 3 ) -1 . Cancer potency from
continuous lifetime exposure was calculated by assuming 240 workdays of a 365 day year and 10 of 20
m 3 /day total air breathed during the workday. Potencies thus expressed are 0.67 (mg-yr/m 3 ) -1 with
upper and lower confidence bounds of 2.5 and 0.14 (mg-yr/m 3 ) -1 . Assumptions of 70 kg body weight,
70 yr lifespan, and 20 m 3 /day breathing rate (CDHS, 1988) result in a cancer potency of 160 (mg/kgday)
-1 with upper and lower 90% confidence bounds of 600 and 30 (mg/kg-day) -1 .
An estimate of cancer potency was also made based on a description of cumulative risk described by
IARC (1982) (CDHS, 1988). IARC (1982) describe risk based on the assumption that the risk varies
linearly with the duration of exposure. IARC (1982) report the data from Zavon et al. (1973) show a
cumulative bladder tumor incidence of 25% among workers exposed to benzidine for 15 years. Under
such an assumption, cancer potency (B) from lifetime (t L = 70 yrs) exposure can be based on the
95