IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

3.2.2 Rat
Groups of 49 male and 49 female Fischer 344/N rats, six weeks of age, were exposed
in inhalation chambers to 0, 10, 30 or 60 ppm [0, 52, 157 or 314 mg/m 3 ] naphthalene
(> 99% pure) for 6 h per day, on five days per week, for 105 weeks. Mean body weights
of all exposed groups of male rats were less than that of the chamber control group
throughout the study, but mean body weights of exposed groups of females were similar
to that of the chamber control group. Survival rates in all exposed groups were similar
to that of the chamber controls. At the end of the study, 24/49, 22/49, 23/49 and 21/49
males and 28/49, 21/49, 28/49 and 24/49 females were alive in the 0, 10, 30 and 60 ppm
groups, respectively. Neuroblastomas of the nasal olfactory epithelium were observed in
0/49, 0/49, 4/48 (p = 0.056, Poly-3 test) and 3/48 male rats and in 0/49, 2/49, 3/49 and
12/49 (p = 0.001, Poly-3 test) females in the 0, 10, 30 and 60 ppm groups, respectively.
In addition, adenomas of the nasal respiratory epithelium were observed in 0/49, 6/49
(p = 0.013, Poly-3 test), 8/48 (p = 0.003, Poly-3 test) and 15/48 (p < 0.001, Poly-3 test)
males and 0/49, 0/49, 4/49 (p = 0.053, Poly-3 test) and 2/49 females in the 0, 10, 30 and
60 ppm groups, respectively. These olfactory neuroblastomas and respiratory epithelium
adenomas had not been observed in the larger database of historical controls in National
Toxicology Program two-year inhalation studies in which animals were fed National
Institute of Health (NIH)-07 diet or in the smaller National Toxicology Program database
[all routes] in which they were fed NTP-2000 diet. In addition to the nasal neoplasms,
the incidences of a variety of non-neoplastic lesions of the nasal tract in both male and
female rats were significantly increased in naphthalene-exposed animals compared with
controls (see Section 4.2.2(b)) (National Toxicology Program, 2000).
3.3 Intraperitoneal administration
3.3.1 Mouse
NAPHTHALENE 387
A group of 31 male and 16 female CD-1 mice received intraperitoneal injections of
a 0.05-M solution of naphthalene [purity unspecified] in dimethyl sulfoxide (DMSO) on
days 1, 8 and 15 of life. The total dose received was 1.75 μmol per mouse. Groups of 21
male and 21 female mice receiving DMSO alone served as vehicle controls. [The
number of mice in the above four groups are reported as the effective number of mice
that survived at least six months of treatment and not the starting number.] Mice were
weaned at 21 days, separated by gender and maintained until termination at 52 weeks, at
which time they were necropsied and gross lesions as well as liver sections were examined
histologically. There was no increase in the incidence of tumours in the naphthalene-treated
mice compared with the vehicle controls (LaVoie et al., 1988).