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EC number: 202-049-5
CAS number: 91-20-3
from RAR, ECB 3003
of single exposure studies: Haemolytic anaemia
is no information on the effects of naphthalene following acute
inhalation or dermal exposure in humans.
oral exposure to naphthalene causes haemolytic anaemia, which may be
fatal. Individuals deficient in G-6-PD are more susceptible to the
effects of naphthalene.
first signs of toxicity are usually seen within 2 days. There is little
quantitative information available, although severe haemolytic anaemia,
which may have proved lethal in the absence of clinical intervention,
was reported in a female who had ingested approximately 6 g naphthalene.
An in vitro study backed up by an in vivo study in rabbits has
demonstrated that the anaemia is caused by the naphthalene metabolite,1-naphthol.
is of low toxicity in rats, with mice being more sensitive. However,
studies in animal models (mainly rats, mice and rabbits) have indicated
that the toxic effects of naphthalene seen in these species are
different from those in humans. Of the species studied, only dogs (in a
poorly conducted study) demonstrated naphthalene-induced haemolytic
anaemia. Rabbits showed signs of haemolytic anaemia with 1-naphthol but
not with naphthalene. It appears that rodents are not suitable animal
models for the acutely toxic human health effects of naphthalene in
relation to haemolytic anaemia.
while the LD50 results from the rat suggest relatively low acute
toxicity in this species, the available information in humans indicates
significant toxicity. Very severe haemolytic anaemia occurred in one
case report (of a 16 year old female) at an estimated single oral dose
of approximately 6 g. It is possible that this represents a lethal dose,
given that a number of blood transfusions were required.[ECB
are a great many case reports in the literature of acute haemolytic
anaemia produced by naphthalene. The signs and symptoms of haemolytic
anaemia associated with naphthalene exposure are well described (e.g.
Gosselin et al., 1984, Mack, 1989).
first signs and symptoms of toxicity are usually dark urine, pallor,
abdominal pain, fever, nausea, vomiting and diarrhoea. On clinical
examination the liver and spleen were enlarged. Haematological effects
are fragmentation of red blood cells with anisocytosis and
poikilocytosis, jaundice, anaemia with a reduction in haemoglobin levels
and haematocrit values and resulting reticulocytosis and leucocytosis.
More severe reactions also include Heinz body formation, haemoglobinuria
and mild methaemoglobinaemia. In young children deaths have occurred due
to kernicterus (a severe neural condition associated with high levels of
bilirubin in the blood). In older
children and adults renal failure may occur. Liver damage has also been
described, but as a rare occurrence.
who are deficient in G-6-PD are particularly sensitive to haemolytic
anaemia produced by naphthalene (Gosselin et al., 1984). This deficiency
is genetically determined and occurs more often in males. The defect
results in an inability by the red blood cell to maintain a balance
between reduced and oxidised glutathione which in turn results in an
increased susceptibility to oxidative attack by exogenous chemicals. It
seems probable that the oxidative attack, following exposure to
naphthalene, can occur following redox cycling of the naphthalene
metabolites 1-naphthol and the quinone. The deficiency is known to be
more common in Blacks,
Italians, Sephardic Jews, Orientals and Filipinos.[HSE/UK
2003, p. 141/142]
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