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Cancers other than of the lung or mesothelioma have
been considered in many studies [ref : 1, 17, 35, 39,
41-44, 48, 51, 55, 60-62, 68-70, 72-74, 76, 83, 87,
89, 92, 93, 96, 97, 99-108]. Some indicated an approximately
two-fold risk with regard to gastrointestinal cancer
in connection with shipyard work [ref: 41,43], and some
increased risk was also seen in association with exposure
to both chrysotile and crocidolite [ref: 103], to crocidolite
[ref: 61,74] or to chrysotile [ref: 87]. Cancer of the
colon and rectum was associated with asbestos exposure
during chrysotile production, with an approximately
two-fold risk [ref: 87]; a similar excess was found
for unspecified asbestos exposure [ref: 104]. Some excess
of ovary cancer has been reported in two studies [ref:
73,76] but not in another [ref: 92]; exposure to crocidolite
was probably more predominant in the studies that showed
excesses. Bile-duct cancer appeared in excess in one
study based on record-linking [ref: 105], and large-cell
lymphomas of the gastrointestinal tract and oral cavity
appeared to be strongly related to asbestos exposure
in one small study covering 28 cases and 28 controls,
giving a risk ratio of 8; however, ten cases and one
control also had a history of malaria [ref: 106]. An
excess of lymphopoietic and haematopoietic malignancies
has been reported in plumbers, pipe-fitters, sheet-metal
workers and others with asbestos exposure [ref: 17,54,107,108].
The relationship between asbestos exposure and smoking
indicates a synergistic effect of smoking with regard
to lung cancer [ref: 1]. Further evaluations indicate
that this synergistic effect is close to a multiplicative
model [ref: 52,109]. As noted previously [ref: 1], the
risk of mesothelioma appears to be independent of smoking
[ref: 47,66], and a significantly decreasing trend in
risk was observed with the amount smoked in one study
[ref: 65].
The studies of the carcinogenic effect of asbestos exposure,
including evidence reviewed earlier [ref: 1], show that
occupational exposure to chrysotile, amosite and anthophyllite
asbestos and to mixtures containing crocidolite results
in an increased risk of lung cancer, as does exposure
to minerals containing tremolite and actinolite and
to tremolitic material mixed with anthophyllite and
small amounts of chrysotile. Mesotheliomas have been
observed after occupational exposure to crocidolite,
amosite, tremolitic material and chrysotile asbestos.
Gastrointestinal cancers occurred at an increased incidence
in groups occupationally exposed to crocidolite, amosite,
chrysotile or mixed fibres containing crocidolite, although
not all studies are consistent in this respect. An excess
of laryngeal cancer has also been observed in some groups
of exposed workers. No clear excess of cancer has been
associated with the presence of asbestos fibres in drinking-water.
Mesotheliomas have occurred in individuals living in
the neighbourhood of asbestos factories and mines and
in people living with asbestos workers.
B. Evidence for carcinogenicity to animals (sufficient)
Asbestos has been tested for carcinogenicity by inhalation
in rats, by intrapleural administration in rats and
hamsters, by intraperitoneal injection in mice, rats
and hamsters and by oral administration in rats and
hamsters. Chrysotile, crocidolite, amosite, anthophyllite
and tremolite produced mesotheliomas and lung carcinomas
in rats after inhalation exposure [ref: 1,110,111] and
mesotheliomas following intrapleural administration
[ref: 1,112]. Chrysotile, crocidolite, amosite and anthophyllite
induced mesotheliomas in hamsters following intrapleural
administration [ref: 1]. Intraperitoneal administration
of chrysotile, crocidolite and amosite induced peritoneal
tumours, including mesotheliomas, in mice [ref: 1,113]
and rats [ref: 1,111,114]. Given by the same route,
crocidolite produced abdominal tumours in hamsters [ref:
115], and tremolite and actinolite produced abdominal
tumours in rats [ref: 110,116-118]. A statistically
significant increase in the incidence of malignant tumours
was observed in rats given filter material containing
chrysotile orally [ref: 1]. In more recent studies,
tumour incidence was not increased by oral administration
of amosite or tremolite in rats [ref: 119], of amosite
in hamsters [ref: 120,121] or of chrysotile in hamsters
[ref: 121]. In two studies in rats, oral administration
of chrysotile produced a low incidence of benign adenomatous
polyps of the large intestine in males (9/250 versus
3/524 pooled controls) [ref: 122] and of mesenteric
haemangiomas (4/22 versus 0/47 controls) [ref: 123].
Synergistic effects were observed following intratracheal
administration of chrysotile and benzo[a]pyrene to rats
and hamsters [ref: 1] and of intratracheal administration
of chrysotile and subcutaneous or oral administration
of N-nitrosodiethylamine to hamsters [ref: 124].
C. Other relevant data
Insulation workers exposed to asbestos 'displayed a
marginal increase' in the incidence of sister chromatid
exchanges in lymphocytes in one study [ref: 125].
Chrysotile did not induce micronuclei in bone-marrow
cells of mice or chromosomal aberrations in bone-marrow
cells of rhesus monkeys treated in vivo. In cultured
human cells, conflicting results were reported for the
induction of chromosomal aberrations and negative results
for the induction of sister chromatid exchanges by chrysotile
and crocidolite; amosite and crocidolite did not induce
DNA strand breaks, and crocidolite was not mutagenic.
Amosite, anthophyllite, chrysotile and crocidolite induced
transformation of Syrian hamster embryo cells, chrysotile
and crocidolite transformed BALB/c3T3 mouse cells, and
chrysotile transformed rat mesothelial cells. Neither
amosite nor crocidolite transformed CH3 10T1/2 cells.
In cultured rodent cells, amosite, anthophyllite, chrysotile
and crocidolite induced chromosomal aberrations, and
amosite, chrysotile and crocidolite induced sister chromatid
exchanges; chrysotile and crocidolite induced aneuploidy
and micronuclei. Chrysotile did not induce unscheduled
DNA synthesis in rat hepatocytes. Amosite, chrysotile
and crocidolite were inactive or weakly active in inducing
mutation in rodent cells in vitro; none were mutagenic
to bacteria [ref: 125].
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