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Siegel and Wason (1986) reviewed a number of case studies to examine the haematological
properties of naphthalene; one day after exposure, Heinz-body haemolytic
anaemia leads to a sharp fall in haemoglobin, haematocrit and red blood cell counts and,
in some cases, to concurrent leukocytosis. Reticulocytosis then follows with a gradual
restoration of normal blood levels, except in cases of severe poisoning.
Individuals with decreased glucose-6-phosphate dehydrogenase activity in their erythrocytes
are sensitive to haemolytic anaemia following exposure to naphthalene,
although toxic reactions have also been observed in individuals without red cell defects.
Four black patients (three male and one female) who had been exposed to naphthalene
were found to have haemolytic anaemia. One of the patients was a newborn whose
mother had ingested mothballs. All four patients had red blood cell glucose-6-phosphate
dehydrogenase deficiency (Zinkham & Childs, 1958).
[The Working Group noted that in all of these cases the amount of naphthalene
ingested was not reported.]
Additional data on the effects of exposure to naphthalene in infants and children are
presented in Section 4.3.1.
4.2.2 Experimental systems
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(a) In-vivo studies with single doses
The oral LD 50 of naphthalene in CD-1 mice was 533 mg/kg bw for males and
710 mg/kg bw for females (Shopp et al., 1984).
Naphthalene causes cataracts in rats (Rathbun et al., 1990; Tao et al., 1991), rabbits
(van Heyningen, 1979) and mice (Wells et al., 1989). Haemolytic anaemia has not been
reported in experimental animals.
The biochemical pathways that modulate the cataractogenicity of naphthalene were
investigated using biochemical probes and naphthalene bioactivation and detoxification
in C57BL/6 and DBA/2 mice (Wells et al., 1989). These mouse strains differ in susceptibility
to the induction of CYP enzymes and the development of naphthalene-induced
cataracts. Intraperitoneal injection of 500–2000 mg/kg bw naphthalene caused cataracts
in C57BL/6 mice in a dose-dependent fashion. 1-Naphthol (56–62 mg/kg bw),
1,2-naphthoquinone and 1,4-naphthoquinone (5–250 mg/kg bw), metabolites of
naphthalene, administered intraperitoneally to these mice were also found to cause cataracts.
Pretreatment of the mice with SKF525A or metyrapone (CYP inhibitors), several
types of antioxidants, the glutathione precursor N-acetylcysteine or the free radicaltrapping
agent, α-phenyl-N-tert-butylnitrone, decreased the incidence of cataracts. Cataracts
were enhanced by pretreatment with phenobarbital and the glutathione depletor
diethyl maleate. DBA/2 mice treated intraperitoneally with naphthalene (2000 mg/kg
bw), 1,2- or 1,4-naphthoquinone or diethyl maleate followed by naphthalene did not
develop cataracts. These results support the hypothesis that the cataractogenesis by
naphthalene in C57BL/6 mice requires CYP-catalysed bioactivation to a reactive intermediate
and that detoxification is dependent upon glutathione. The lack of cataract