IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

Airways microdissected from male Swiss Webster mice by filling the trachea with
1% agarose were maintained in culture for 8 h. When these explants were incubated with
0.5 mM naphthalene, the cytotoxic response of the bronchial epithelium was identical to
the vacuolation and exfoliation observed in vivo in bronchioles of mice 24 h after intraperitoneal
administration of naphthalene (100 or 300 mg/kg bw). Pre-incubation with
piperonyl butoxide prevented naphthalene-induced cytotoxicity (Plopper et al., 1991).
To determine whether the formation of reactive metabolites of naphthalene in
defined target and non-target regions of the lung correlates with the susceptibility of
these areas to naphthalene toxicity, the binding of metabolites in various cell types and
in various subcompartments of the mouse lung was investigated. Binding was greater in
distal bronchioles and isolated Clara cells incubated with [ 3 H]naphthalene than in
explants of mouse trachea or bronchus. Binding was also greater in mouse Clara cells
than in mouse hepatocytes (non-target cells) or rat trachea cells (non-susceptible
species). There was a good correlation between cellular susceptibility to toxicity and the
amount of reactive metabolite bound in vitro (Cho et al., 1994a,b).
4.3 Reproductive and developmental effects
4.3.1 Humans
NAPHTHALENE 409
Sensorineural hearing loss was reported in an infant with neonatal hyperbilirubinaemia
from haemolysis due to glucose-6-phosphate dehydrogenase deficiency and
naphthalene exposure. The baby had normal hearing at 13 days of age, but had developed
profound bilateral hearing loss by seven months of age. On the day of admittance to
hospital, the infant had been dressed in clothes and placed on a blanket that had all been
stored in naphthalene mothballs for five years (Worley et al., 1996).
In a survey of neonatal jaundice in association with household drugs and chemicals
in Nigeria, the overall incidence of jaundice did not differ significantly in neonates from
households with or without a history of exposure to drugs or chemicals. Severe neonatal
jaundice, as judged by the need for exchange blood transfusion or death of the infant,
was, however, significantly more frequent among neonates from families with a history
of naphthalene exposure than in those without (Familusi & Dawodu, 1985). [The
Working Group noted that aflatoxin-contaminated food is a possible confounder in this
populaton.]
Melzer-Lange and Walsh-Kelly (1989) reported naphthalene-induced haemolysis in
a black female infant deficient in glucose-6-phosphate dehydrogenase. Fourteen of 24
children identified as having glucose-6-phosphatase deficiency were diagnosed with
haemolysis associated with exposure to naphthalene-containing moth-repellents
(Santucci & Shah, 2000).
Acute haemolysis with the presence of Heinz bodies and fragmented erythrocytes
occurred following inhalation of naphthalene in 21 newborn Greek infants, 12 of whom