19085-1701857-UL_Prop_65_Test_Results_2019
Table Of Contents
CA Prop 65 Cumene NSRL February 11, 2019 Page 10 | 12
APPENDIX: METHODOLOGY USED TO DERIVE THE NSRL FOR CUMENE
Modeling was based on the linearized multistage cancer model for the cumene cancer studies
which showed both a significant dose-related trend in the data and had at least two doses with
response levels in excess of the control were used for cancer slope factor modeling. Once all
the available cumene cancer data was modeled, the geometric mean from the most
conservative cancer slope factors was selected as a reasonable conservative or health
protective estimate. Specifically, the most sensitive animal cancer slope factors (CSF) were
determined for the male and female B6CF1
1
mice using the linearized multistage cancer model
for lung tumors (alveolar/bronchiolar adenoma or carcinoma) data. The tumor results included
in the analysis along with animal cancer slope factors are listed in Table 3.
A.1. Calculation of lifetime average daily dose
The lifetime average dose in units of mg/kg-day was calculated for each of the relevant dose
groups, based on the dose level, duration and regimen described in the experiments above.
Average body weights for female B6CF1
1
mice (0.043 kg) male B6CF1
1
mice (0.044 kg) female
F344 rats (0.252 kg), and male F344 rats (0.410 kg), were based on control animal body
weights reported by NTP (2009). The inhalation rates (IR) for mice and rats was calculated
based on the equations of Anderson et al. (1983), which was derived using experimental data
on animal breathing rates (mg/m
3
) and corresponding body weights (kg):
IR
= 0.105 ×
(
bw
÷ 0.113
)
(Equation A1)
IR
= 0.0345 ×
(
bw
÷ 0.025
)
The air concentration (C
air
) in units (mg/m
3
) was then multiplied by the inhalation rate (IR in
m
3
/day) for mice and rats and divided by the respective body weight, and then multiplied by
6.2/24 to account for the hours of exposure per day and by 5/7 to account for a five day per
week dosing. The equation for lifetime average dose (D
LTA
) in units (mg/kg-day) is therefore:
D
LTA
= mg/m
3
x
IR
rodent
bw
rodent
(m
3
/day)
kg
x
6.2
24
x
5
7
(Equation A2)