The Toxicologist - Society of Toxicology

odent-specific disease, was observed in males (7.5 mg/mL) and females (15
mg/mL), with a greater incidence and severity in males. In male rats, a statistically
significant trend of increasing CPN severity with increasing MTBE concentration
was observed. Neoplasms of noteworthy incidence were limited to the brain.
Astrocytomas were identified in study animals (9/460) with incidences in male rats,
continuously exposed to MTBE, of 1/50, 1/50, 1/50, and 4/50 for the 0, 0.5, 3,
and 7.5 mg/mL groups, respectively. Statistical analysis indicated a marginally significant
(p=0.037) trend in male rats, however this trend was not considered biologically
significant because the observed incidences of astrocytoma fell within historical
control ranges published in the literature for Wistar rats and the brain has
not been identified as a target organ in previous MTBE carcinogenicity studies.
1952 A COMPARATIVE RISK EVALUATION OF MTBE AND
OTHER COMPOUNDS (INCLUDING NATURALLY
OCCURRING COMPOUNDS) IN DRINKING WATER IN
NEW HAMPSHIRE.
L. A. Beyer, R. L. Mattuck, S. Thakali and B. D. Beck. Gradient, Cambridge, MA.
We conducted a comparative cancer risk assessment for several constituents in NH
drinking water. The overall aim was to present a relative ranking of risks, not to
evaluate whether permissible limits were exceeded. Using standard risk assessment
methodology, we calculated relative cancer risks from exposure to ten VOCs (including
MTBE) detected in NH public water supplies, as well as arsenic, radium-
226, radium-228, and radon. We evaluated exposures to an adult resident via ingestion
of water, dermal contact with water while showering, and inhalation of
volatilized compounds in the home. For arsenic, we evaluated only the ingestion
and dermal pathways; for the radionuclides, we evaluated only the ingestion and inhalation
pathways. This comparative risk evaluation is similar to one conducted by
Williams et al. (2002, 2004) for water supplies in California. From this analysis, we
concluded that the upper bound cancer risk from exposure to MTBE in drinking
water is lower than the risks from nine other VOCs detected in NH drinking water
supplies, and several thousand times lower than the risks from exposure to naturally
occurring constituents including arsenic, radium isotopes, and radon. Even with
the risk weighted by detection frequency, MTBE exhibits the third lowest risk of
the VOCs and exhibits a relative risk two orders of magnitude lower than the relative
risk for the disinfection byproducts (bromodichloromethane, chloroform, and
dibromochloromethane).
1953 SUB-CHRONIC NAPHTHALENE INHALATION CAUSES
A DECREASE IN P53 CODON 271 CAT MUTANT
FRACTION IN THE NASAL RESPIRATORY
EPITHELIUM OF MALE RATS.
F. Meng 1 , Y. Wang 1 , M. B. Myers 1 , B. A. Wong 2 , E. A. Gross 2 , H. J. Clewell 3 ,
D. E. Dodd 2 and B. L. Parsons 1 . 1 Division of Genetic and Molecular Toxicology,
National Center for Toxicological Research/U.S. FDA, Jefferson, AR, 2 Division of
Toxicology and Preclinical Studies, The Hamner Institutes for Health Sciences,
Research Triangle Park, NC and 3 Center for Human Health Assessment, The Hamner
Institutes for Health Sciences, Research Triangle Park, NC.
This study sought to gain mechanistic insight into naphthalene-induced nasal carcinogenesis
through dose response analysis of a tumor-relevant endpoint. Levels of
p53 codon 271 CGT to CAT mutation were measured in rat nasal respiratory and
olfactory epithelium following whole-body exposure to naphthalene (NA) by allelespecific
competitive blocker-PCR. Male and female, 6-7 week-old F344 rats were
exposed to 0, 0.1, 1.0, 10, and 30 ppm NA vapor for 13 weeks (6 h/day, 5
days/week), using 5 rats/group. For control groups, the geometric mean p53 mutant
fraction (MF) levels in nasal epithelium ranged between 2.05 X 10 -5 and 3.05
X 10 -5 . No significant dose-related changes in p53 MF were observed in the olfactory
or respiratory epithelia of female rats. However, statistically significant treatment-related
differences were observed in male respiratory and olfactory epithelium,
with the p53 MF in the respiratory epithelium of male rats exposed to 30
ppm NA significantly (p