home edit2 whole TSD November 2002 PDF format - OEHHA

data. If several data sets (dose and tumor incidence) are available (different animal species, strains,
sexes, exposure levels, exposure routes) for a particular chemical, the data set used in the model is the
set where the incidence is statistically significantly higher than the control for at least one test dose level
and/or where the tumor incidence rate shows a statistically significant trend with respect to dose level.
The data set generating the highest lifetime cancer risk estimate (q * 1 ) is chosen where appropriate. An
example of an inappropriate data set would be a set which generates an artifactually high risk estimate
because of a very small number of animals used. If there are 2 or more data sets of comparable size for
a particular chemical that are identical with respect to species, strain, sex and tumor sites, the geometric
mean of q *
1 estimated from each of those data sets is used for risk estimation. The geometric mean of
numbers A 1 , A 2 , …, A m is defined as A 1 * A 2 * … * A m ) 1/m . US EPA assumes that mg/surface area/day
is an equivalent dose between species. Surface area is further assumed to be proportional to the 2/3
power of the weight of the animal in question. Equivalent dose is therefore computed using the following
relationship:
d =
1e*
m
Le
* W
2/
3
where L e = experimental duration, l e = exposure duration, m = average dose (mg/day) and W = average
animal weight. Default average body weights for humans, rats and mice are 70, 0.35 and 0.03 kg,
respectively.
Exposure data expressed as ppm in the diet are generally converted to mg/day using the relationship m
= ppm * F * r, where ppm is parts per million of the chemical in the diet, F is the weight of the food
consumed per day in kg, and r is the absorption fraction (assumed to be 1 in the absence of data
indicating otherwise). A proportionality exists between the weight of food consumed, calories required,
animal surface area, and the 2/3 power of the animal weight, so that:
m ∝ ppm * W 2/3 m
* r, or ∝ ppm
rW 2/ 3
The relationship could lead to the assumption that dietary ppm is an equivalent exposure between
species. However, US EPA believes that this assumption is not justified, since the calories/kg food
consumed by humans is significantly different from that consumed by laboratory animals (primarily due
to differences in moisture content). US EPA uses an empirically derived food factor, f = F/W, which is
the fraction of a species’ body weight consumed per day as food. The f values for humans, rats and
mice used by US EPA are 0.028, 0.05 and 0.13, respectively. Dietary exposures expressed as
concentrations in ppm are converted to mg/surface area using the following relationship:
m
r * W
2/
3
= ppm * F
2/3
W
= ppm * f * W
2/3
W
= ppm * f * W 2/3
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