IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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IARC MONOGRAPHS VOLUME 82
liver. Pretreatment with diethyl maleate increased the binding of radiolabelled material,
while piperonyl butoxide and SKF 525A decreased the binding by 75% and 50%, respectively
(Warren et al., 1982).
O’Brien et al. (1985) studied the species-dependent pulmonary toxicity of naphthalene.
Male Swiss T.O. mice (weighing 20–25 g) and male Wistar-derived rats (weighing
200–225 g) were given intraperitoneal doses of naphthalene at 200–600 and 400–1600
mg/kg bw, respectively. The lungs, livers, kidneys and spleen were removed 24 h after
the injection and prepared for light microscopy. In mice, there was selective damage to
the non-ciliated bronchiolar epithelial (Clara) cells at low doses of naphthalene. At high
doses of naphthalene, vascular and hydropic degeneration of cells in the proximal convoluted
tubule was observed together with protein casts in the collecting ducts. Tissue
damage was not observed in the lung, liver or kidney of rats that received up to
600 mg/kg bw naphthalene. Non-protein sulfhydryl was depleted in a time-dependent
manner in the lungs, liver, spleen and kidneys of naphthalene-treated mice, but only in
the lung and liver of treated rats. Administration of 1-naphthol (200 mg/kg bw to mice
and 200–250 mg/kg bw to rats) did not lead to depletion of non-protein sulfhydryl levels
or tissue damage in the liver, lung or kidney of either species. Covalent binding and
metabolism of naphthalene were approximately 10-fold greater in mouse lung microsomes
than in rat lung microsomes. The authors attributed the differences in naphthaleneinduced
toxicity in mice and rats to differences in metabolism between the two species.
Intraperitoneal injection of 1.6–4.7 mmol/kg bw (200–600 mg/kg bw) naphthalene in
male ddY mice resulted in a dose-dependent increase in lung damage mainly in the
bronchiolar region, with no damage following a dose of 0.78 mmol/kg (100 mg/kg bw).
The response was enhanced by diethyl maleate treatment. Increasing the dose of naphthalene
from 1 to 3 mmol/kg bw resulted in a decrease in pulmonary glutathione levels.
Naphthalene did not affect lipid peroxidation or phospholipid content in the lungs. In
lung slice preparations, the covalent binding of naphthalene was increased or decreased
when the mice had been pretreated with inducers or inhibitors of CYP enzymes, respectively
(Honda et al., 1990).
A single intraperitoneal injection of 2 mmol/kg bw naphthalene in ddY mice resulted
in a 50% reduction of carbonyl reductase activity and microsomal mixed-function oxidase
activities in the Clara cells (Matsuura et al., 1990).
Naphthalene was given by intraperitoneal injection to Swiss Webster mice
(0–400 mg/kg bw), Syrian golden hamsters (0–800 mg/kg bw) and Sprague-Dawley rats
(0–1600 mg/kg bw). The animals were killed 24 h later for identification of the specific
sites of the respiratory tract affected by the treatment (nasal cavity and tracheobronchial
airway tree). In mice, the injury to the tracheobronchial epithelium was dose-dependent
and Clara cell-specific. At 50 mg/kg bw, naphthalene produced swelling and vacuolation
of Clara cells in terminal bronchioles. The number of terminal bronchioles with vacuolated
Clara cells and the number of Clara cells within the terminal bronchioles that
showed vacuolation increased after 100 mg/kg bw naphthalene. Following 200 and
300 mg/kg bw, almost all of the non-ciliated cells lining the terminal bronchioles in mice