IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

394
IARC MONOGRAPHS VOLUME 82
and 13.6% in the expired air. The primary urinary metabolites identified were 2,7-dihydroxynaphthalene
(31.1% of the total radioactivity in the first 12 h), 1,2-dihydroxynaphthalene
(7, see Figure 1) (17.2%), 1,2-naphthoquinone (8, see Figure 1) (11.4%),
2-naphthol (4.3%) and 1-naphthol (3.4%). The parent compound naphthalene accounted
for 0.3% of the radioactivity (Turkall et al., 1994). [The Working Group noted that
2,7-dihydroxynaphthalene has not been identified as a major metabolite in other studies.]
Kilanowicz et al. (1999) studied the distribution, metabolism and excretion of
tritiated naphthalene given intraperitoneally at a dose of 20 mg/kg bw to male IMP:Wist
rats. Approximately 88% of the radioactivity was excreted in urine (68%) and faeces
(20%) in the first 72 h, with maximum blood concentrations observed 2 h after dosing.
The elimination of radioactivity from the blood was biphasic with half-lives of 0.8 and
99 h. [The Working Group noted that the 99-h half-life component may have been due to
tritium exchange.] The highest initial tissue concentrations were found in fat, liver and
kidneys. Urinary metabolites were identified as primarily the parent naphthalene,
1-naphthol and 2-naphthol with smaller amounts of 1,2-dihydro-1,2-dihydroxynaphthalene
(1,2-dihydrodiol) and methylthionaphthalenes.
Sartorelli et al. (1999) investigated the percutaneous penetration of naphthalene from
lubricating oil in vitro using full-thickness monkey skin. The flux for naphthalene was
0.274 nmol/cm 2 per hour, which was higher than that for acenaphthene, fluorene, anthracene,
phenanthrene, pyrene and chrysene. Kanikkannan et al. (2001b) examined the
percutaneous permeation of naphthalene in JP-8 + 100 jet fuel, which contained 0.26%
(w/w) naphthalene and was spiked with [ 14 C]naphthalene, using a pig ear skin model.
The steady-state flux was 0.42 μg/cm 2 per hour, similar to that of nonane but less than
for tridecane.
(b) Metabolism — species comparison
Corner and Young (1954) compared the urinary metabolites of naphthalene in rats,
rabbits, mice and guinea-pigs [strains unspecified] following administration of a single
dose of naphthalene (500 mg/kg bw) either orally or by intraperitoneal injection. 1-Naphthol
and its glucuronide and sulfate were identified in the urine of all four species (with
the exception of the glucuronide in guinea-pigs). 2-Naphthol was detected in all four
species but no conjugates of this metabolite were found. Although 1,2-dihydro-1,2-dihydroxynaphthalene
(1,2-dihydrodiol) was found in the urine of all four species, 1,2-dihydroxynaphthalene
was present only in urine of guinea-pigs. Rabbits and rats excreted
more 2-naphthol than 1-naphthol, guinea-pigs excreted 1- and 2-naphthol in equal
amounts and mice excreted more 1-naphthol than 2-naphthol. As in humans, a precursor
of 1-naphthyl mercapturic acid has been detected as a urinary metabolite in all rodent
species tested (Boyland & Sims, 1958); the amounts of this metabolite present in the
urine of mice, rats and hamsters were greater than those observed in guinea-pigs, which
were greater than those in humans. However, these data did not take into consideration
the widely different doses given: mice, rats, hamsters, guinea-pigs and humans received
total doses of 20, 100, 100, 400 and 500 mg per animal, respectively. Chen and Dorough