home edit2 whole TSD November 2002 PDF format - OEHHA

indicate that the most sensitive site(s) are not relevant to human cancer induction, or represent data sets
with unusually wide error bounds. As an alternative, where several equally plausible results are available
and are sufficiently close to be regarded as concordant, the geometric mean of all such estimates may be
used.
Pharmacokinetic modeling, which would allow the comparison of different routes and correct for
nonlinearities in the relationship between applied and internal dose, was not available for the mouse.
Therefore, the potency estimates obtained in the rat were preferred for risk assessment purposes.
Because the results in rats and mice are comparable, the use of the rat data was consistent with the
policy of selecting appropriately sensitive species as the basis for the estimate of potency in humans.
Table 4:
Dose Response Parameters for MTBE Carcinogenicity Studies
a) Inhalation studies - ppm in air as dose metric
Species Sex Tumor site and type LED 10
(ppm)
CSF
(ppm -1 )
mouse a female hepatocellular adenoma + carcinoma 320 3.2 × 10 -4
male hepatocellular adenoma + carcinoma 140 7.0 × 10 -4
rat b male renal tubular cell adenoma + carcinoma 240 4.2 × 10 -4
testicular interstitial cell tumors 46 2.2 × 10 -3
a Burleigh-Flayer et al. 1992, Bird et al. 1997
b
Chun et al., 1992; Bird et al., 1997.
Assumed: Data reassessment by U.S. EPA (1994c, 1995c).
Duration correction based on (t e /t l ) 3 : t l = 104 weeks for both rats and mice.
Interspecies correction: ppm equivalency.
b) Rat oral and inhalation studies - Equivalent oral dose as dose metric
Route Sex Tumor site and type LED 10
(mg/kg-day)
CSF
(mg/kg/day) -1
Inhalation a Male Male renal tubular cell adenoma + carcinoma 55 1.8 × 10 -3
Testicular interstitial cell tumors 11 8.7 × 10 -3
Gavage b Male Leydig cell tumors
Original 1995 report 76 1.38 × 10 -3
Revised 1998 data 64 1.55 × 10 -3
Female Leukemia/lymphoma
Original 1995 report 49 2.03 × 10 -3
Revised 1998 data 48 2.09 × 10 -3
a
Chun et al., 1992.
b Belpoggi et al., 1995, 1998.
Assumed: Data reassessment by U.S. EPA (1994c, 1995c) for Chun et al. (1992) study.
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