home edit2 whole TSD November 2002 PDF format - OEHHA

y inhalation is similar for rats and humans and if the standard assumption that an average adult human
has a body weight of 70 kg and an average air intake of 20 m 3 per day is used, an oral intake of 1
mg/kg/day lead is equivalent to an inhalation exposure of 3,500 µg/m 3 for 24 hr. Using the latter units,
the 95% UCL for q 1
equals 2.4 × 10 -6 (µg/m 3 ) -1 , which assumes equivalent absorption by the 2 routes.
If there is approximately 5 times higher absorption by the respiratory tract compared to the
gastrointestinal tract (Owen, 1990), the inhalation risk can be multiplied by 5 and the corrected
inhalation unit risk is 1.2 × 10 -5 (µg/m 3 ) -1 .
To derive a range of risks, the study by Koller et al. (1985), which showed the greatest sensitivity to
lead’s carcinogenicity, was selected. In that study, 13 out of 16 male rats drinking water containing
2600 ppm lead acetate developed renal tumors, compared to 0 of 10 in controls. The resulting human
equivalent dose (HED) was calculated as 60.1 mg/kg-day. Using the GLOBAL86 program, an MLE
for q 1
of 0.0279 (mg/kg-day) -1 and a 95% UCL, q 1
* of 0.0455 (mg/kg-day) -1 were obtained. The
latter potency was divided by 3500 to obtain a preliminary inhalation unit risk of 1.3 × 10 -5 (µg/m 3 ) -1 ,
which, when corrected for the 5-fold greater absorption by inhalation compared to ingestion in humans
(Owen 1990), yielded a final inhalation unit risk of 6.5 × 10 -5 (µg/m 3 ) -1 .
Therefore, the 95% UCL obtained for the range of inhalation unit risks is 1.2 × 10 -5 (µg/m 3 ) -1 to 6.5 ×
10 -5 (µg/m 3 ) -1 . The best value of the cancer unit risk for air was selected as 1.2 × 10 -5 per µg/m 3 .
Table 2:
Lead in food (ppm)
Kidney tumors in rats fed lead a
Animal dose
(mg/kg-day)
HED b
(mg/kg-day)
Added Measured exp d tumors
Number of rats c % % died
0 3 0.225 0.038 20 f 0 0 50
0 5 0.39 0.067 100 0 0 37
10 18 1.40 0.238 50 0 0 36
50 62 4.78 0.818 50 0 0 36
100 141 10.88 1.86 50 0 0 36
500 548 42.27 7.22 50 5 10 52
1000 e 1130 79.65 13.6 20 f 10 50 50
2000 e 2102 162 27.2 20 f 16 80 80
a Data from Azar et al. (1973).
b Human Equivalent Dose = daily dose × (70/0.35) 1/3 .
c Among similar size groups of female rats, kidney tumors were seen only in 7 of 20 animals in the 2000 ppm group.
d Number of animals exposed to indicated level of lead in food.
e The rate of body weight gain was depressed in both groups. Since mortality was not increased in the 1000 ppm
group, it can be considered a Maximally Tolerated Dose (MTD).
f The groups with only 20 rats per dose level were also studied for 2 years but were begun several months after the
other dose groups.
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