IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

these naphthols as metabolites. The frequency of detection was 86% for 1-naphthol and
81% for 2-naphthol. The mean concentrations were 15 and 5.4 μg/g creatinine, respectively.
Concentrations of 1-naphthol ranged up to 1400 μg/g creatinine.
Yang et al. (1999) examined the relationship between certain enzyme polymorphisms
and naphthalene metabolism in 119 men who were not occupationally
exposed to polycyclic aromatic hydrocarbons. A polymorphism in exon 7 of the CYP1A1
gene was not related to urinary naphthol excretion. Smokers with the c1/c2 or c2/c2
genotype in CYP2E1 excreted higher concentrations of 2-naphthol in the urine than
smokers with the c1/c1 genotype. Smokers deficient in glutathione S-transferase M1
(GSTM1) showed higher urinary concentrations (without correction for creatinine) of
both 1-naphthol and 2-naphthol.
Nan et al. (2001) examined the effects of occupation, lifestyle and genetic polymorphisms
of CYP1A1, CYP2E1 and the glutathione S-transferases GSTM1 and GSTT1
on the concentrations of 2-naphthol in the urine of 90 coke-oven workers in comparison
with 128 university students. The urinary excretion of 2-naphthol was higher in the cokeoven
workers (7.69 μmol/mol creatinine) than in the students (2.09 μmol/mol creatinine).
In the control group, the excretion was higher in smokers (3.94 μmol/mol creatinine)
than in nonsmokers (1.55 μmol/mol creatinine). Urinary 2-naphthol concentrations
were higher in coke-oven workers with the c1/c2 or c2/c2 genotypes than in those with
the more common c1/c1 genotype of CYP2E1. Urinary 2-naphthol concentrations were
also higher in the urine of GSTM1-null workers than in GSTM1-positive workers.
4.1.2 Experimental systems
(a) Absorption, distribution and excretion
NAPHTHALENE 393
Early studies indicated that in rats naphthalene is well absorbed from the gastrointestinal
tract (Chang, 1943). When naphthalene was fed to white male rats (weight,
about 300 g) [strain unspecified] at a concentration of 1% (w/w) in the diet, none was
detected in the faeces. Similarly, when it was administered as a single dose by stomach
tube (0.1 g), it was not measurable in the faeces.
Eisele (1985) examined the distribution of [ 14 C]naphthalene in laying pullets, swine
and dairy cattle following oral administration. In pullets given a dose of 0.44 mg, the
major site of deposition was the kidney followed by fat, lung and liver. Following acute
administration of 2.46 mg in swine, the major site of deposition was fat, where the level
was up to 10 times higher than that in liver. After chronic administration (0.112 mg per
day for 31 days), the lung, liver and heart were major sites of accumulation. In cows,
chronic exposure (5.115 mg per day for 31 days) led to deposition primarily in the liver.
When [ 14 C]naphthalene was applied dermally (3.3 μg/cm 2 ; total dose, 43 μg) to male
Sprague-Dawley rats, the plasma half-life for absorption was 2.1 h and that for elimination
was 12.8 h. The highest concentration of radioactivity 48 h after dosing was found
in the skin followed by ileum, duodenum and kidney. Seventy per cent of the
radioactivity was found in the urine in the first 48 h, with 3.7% appearing in the faeces