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EC number: 204-066-3
CAS number: 115-11-7
Members of the butenes category have a low potential for carcinogenicity. Carcinogenicity studies carried out on 2-methylpropene were reported to produce an increase in thyroid follicular cell tumours. The thyroid tumours occurred only in male rats at the highest exposure concentration (8000 ppm: 18,359 mg/m3) at an incidence slightly above the laboratory historical incidence in control animals and no tumours were observed in female rats or male and female mice. As all members of the butenes category are not genotoxic, if 2-methylpropene did cause an increase in thyroid tumors in male rats, a threshold mechanism is likely to be involved and the relevance of tumours of this type to human health is low.
of the butenes category have a low potential for human carcinogenicity
and therefore do not warrant classification under GHS/CLP.
of the butenes category are flammable gases at room temperature and
therefore significant exposure via the dermal or oral routes is
unlikely. Inhalation exposure is the most appropriate route for
studies via inhalation exposure are available for 2-methylpropene (also
called isobutylene). F344 Rats and B6C3F1 mice were exposed by
inhalation at 0, 500, 2,000 or 8,000 ppm (1147, 4589, 18,359 mg/m3),
for 105 weeks (NTP 1998). In rats, treatment-related non-neoplastic
findings were limited toincreased
kidney weights, hyaline degeneration of the olfactory epithelium andhypertrophy
of goblet cells lining the nasopharyngeal ductin
mice, treatment-related non-neoplastic findings were limited toincreasedhyaline
degeneration of the olfactory and respiratory epithelium.These
findings were generally considered to be of low toxicological
significance and are discussed in detail in Section 7.5 (Repeated dose
toxicity). The major urinary metabolite of 2-methylpropene
(2-hydroxyisobutyric acid: HIBA) was measured in the urine of both
species as an indicator of isobutene exposure, these results are
discussed in the Toxicokinetics section.
were no treatment-related neoplasms in female rats or male and female
mice. The NTP concluded that there was no evidence of carcinogenic
activity of isobutene in female rats or male and female mice exposed to
500, 2,000, or 8,000 ppm. A NOAEC of 8000 ppm (18,359 mg/m3) for
carcinogenicity in female rats, male mice and female mice was
established based on these results.
incidence of thyroid gland follicular cell carcinoma in male rats
exposed to 8000 ppm was increased compared to the chamber control group
(1/48, 0/48, 0/48, 5/50 at 0, 500, 2000 and 8000 ppm respectively) and
exceeded the historical control range. The NTP therefore concluded that
there was some evidence of carcinogenic activity of 2-methylpropene in
male rats and established a NOAEC of 2000 ppm (4589 mg/m3) for
carcinogenicity in male rats based on the thyroid follicular cell
carcinomas. The relevance of the thyroid follicular tumours for human
cancer risk is questionable as the tumours occurred in male rats only
and not in either sex in mice. There were no precursor lesions, no
dose-response relationship, the tumours were singular and unilateral,
did not form metastases and there was no increase in liver weight
indicating a secondary mechanism. In addition, the thyroid was not a
target organ in repeat dose studies in rats. Although the 10% incidence
of tumours was outside the historical control at the time, reported to
be 0-4% (NTP 1998, Haseman et al 1998), a carcinogenicity study on
propylene (NTP 1985) had a 7% incidence of thyroid follicular carcinomas
in the control group, further diminishing the significance of the
incidence with 2-methylpropene and suggesting that the tumor findings
may have been spurious. IARC (1999) published guidance noting that no
non-radioactive chemical exposure is known to cause thyroid follicular
carcinomas in humans. It concluded that agents causing thyroid neoplasms
in rodents by hormonal imbalance must be non-genotoxic. Although studies
investigating hormonal imbalance have not been conducted,
2-methylpropene is not genotoxic, indicating if 2-methylpropene did
cause an increase in thyroid tumors in male rats, that a non-genotoxic
mechanism, likely to have a threshold, is involved and the relevance of
tumours of this type to human health is low.
is no data on the carcinogenicity of the butenes in humans.
Toxicokinetic data on members of the butenes category (see
Toxicokinetics Section), indicate that humans have the lowest capacity
for oxidative metabolism and the highest for detoxification pathways.
In conclusion, as no tumours were observed
in female rats or male and female mice and the thyroid tumours observed
only in male rats were either spurious or of questionable relevance to
humans. As all members of the butenes category are not genotoxic,
members of the butenes category have a low potential for human
JK, Hailey JR, Morris and RW (1998). Spontaneous neoplasm incidences in
Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a
National Toxicology Program update.Toxicol
Pathol, 26, 428-441
(1985). NTP Toxicology and Carcinogenesis Studies of Propylene (CAS No.
115-07-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). Natl
Toxicol Program Tech Rep Ser, 272, :1-146
Sci Publ. (1999). Agents that induce epithelial neoplasms of the urinary
bladder, renal cortex and thyroid follicular lining in experimental
animals and humans: summary of data from IARC monographs volumes 1-69.
;Ed Wilbourn JD, Partensky C, Rice JM. 147,191-209.
Carcinogenicity: via inhalation route (target organ): glandular:
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