IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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had deficient glucose-6-phosphate dehydrogenase activity in the erythrocytes (Valaes
et al., 1963).
Two case reports of haemolytic anaemia in newborn infants secondary to maternal
ingestion of mothballs or inhalation exposure to naphthalene have been reported. This
indicates that naphthalene and/or its metabolites can pass the placenta (Anziulewicz
et al., 1959; Athanasiou et al., 1997). [The Working Group noted that the exposure
concentration of naphthalene was not reported.]
4.3.2 Experimental systems
IARC MONOGRAPHS VOLUME 82
(a) Developmental toxicity studies in vivo
In CD-1 mice given 300 mg/kg bw naphthalene per day by gavage on gestation days
7–14, maternal lethality was increased, maternal weight gain was decreased and the
average number of live offspring per litter was decreased. There was no concomitant
increase in the number of dead pups, suggesting that the smaller litter size was due to
early embryonic resorption (Plasterer et al., 1985).
In a teratogenicity study in New Zealand white rabbits treated by gavage with up to
120 mg/kg bw on gestation days 6–19, no signs of developmental or maternal toxicity
were found (Navarro et al., 1992).
When Sprague-Dawley rats were given intraperitoneal injections of 395 mg/kg bw
naphthalene per day on days 1–15 of gestation, no evidence of maternal toxicity or
developmental toxicity was found (Hardin et al., 1981).
Some indications of developmental toxicity were observed when Sprague-Dawley
rats were given up to 450 mg/kg bw naphthalene per day by gavage on gestational days
6–15. Maternal weight gain was reduced in the groups that received 150 and 450 mg/kg
bw per day. There was a significant trend towards decreased fetal body weight and
towards an increased percentage of adversely affected implants per litter (i.e., non-live or
malformed). An increased incidence of visceral malformations was reported, especially
enlarged ventricles of the brain. The percentage of malformed fetuses per litter seen in
the 450-mg/kg bw group was 2.5 times greater than in controls, but this difference was
not significant (Navarro et al., 1991).
(b) Developmental toxicity studies in vitro
Preimplantation embryos of ICR mice exposed in vivo by intraperitoneal injection of
the mother with 14 or 56 mg/kg bw naphthalene on gestational day 2 were collected on
gestational day 3.5. Their subsequent in-vitro growth was markedly reduced during 72 h
of culture. The viability and implantation capacity were also significantly inhibited (Iyer
et al., 1990).
In a study of the role of biotransformation on the rodent in-vitro preimplantation
embryotoxicity of naphthalene, no toxic effects were observed in the absence of a rat S9
activation system in the culture medium. In the presence of the S9 system, naphthalene
caused concentration-dependent embryolethality (approximate LC 50, 0.18 mM). This