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EC number: 204-826-4
CAS number: 127-19-5
Clinical pathology was evaluated
at 3,6,12,18 months; hepatic cells proliferation was examined at two
weeks and three and twelve months. No compound-related effects on
survival were observed. There were no compound-related effects on body
weight or weight gain at any concentration. There were no
compound-related adverse effects on the incidence of clinical signs of
toxicity. No hematological changes were observed. Compound-related
morphological changes were observed in the liver. Exposure to 100 or 350
ppm produced increased absolute and/or relative LIVER WEIGHT (350 ppm
female only), accumulation of LIPOFUSCIN/HEMOSIDERIN in KUPFFER CELLS
and CENTRILOBULAR SINGLE CELL NECROSIS. Female mice exposed to 350 ppm
had an increase incident of BILATERAL, DIFFUSE RETINAL ATROPHY. No
increase in hepatic cells proliferation was seen at any exposure
purpose of the study was to evaluate the oncogenic potential of the test
substance in mice when administered by inhalation. Groups of 78 male and
female Crl:CD-1®BR mice were exposed to either 0, 25, 100, or 350 ppm
test substance for six hours per day, five days per week, for up to 18
months (mice). Chamber atmospheres were analysed during the exposure
period for test substance concentration, temperature, humidity, and
airflow rate. Body weights were obtained weekly during the first three
months of the study and every other week for the remainder of the study.
Clinical signs of toxicity were monitored throughout the study. An
ophthalmological examination was performed on all animals prior to study
start. All surviving mice were examined prior to their respective final
sacrifices. Haematological evaluations were conducted on mice at
approximately 3, 6, 12, and 18 months. Interim sacrifices to determine
the rate of hepatic cell proliferation were conducted on approximately
five mice per sex per concentration and occurred on test days 26, 87,
and 384. All surviving mice underwent gross necropsy after approximately
18 months of exposure to the test substance. Selected tissues were
weighed and tissues were collected for microscopic evaluation.
overall mean concentrations of test substance in the exposure chambers
for the two-year test period were 0.0, 25.2, 101.0, and 350.5 ppm. Mean
chamber temperatures generally ranged between 16-29°C. Mean chamber
relative humidity generally ranged between 20-65%. Mean chamber air flow
ranged between 738-1046 L/min.
were several compound-related effects observed in mice exposed to the
test substance. Male and female mice did not exhibit compound-related
effects on body weight or body weight gain at any exposure concentration.
were no adverse, compound-related effects on the incidence of clinical
signs of toxicity, on the incidence of ophthalmoscopically observable
ocular lesions, or on survival in mice of either sex at any exposure
effects on haematology parameters in mice were not observed. There were
several compound-related effects observed in the livers of mice exposed
to the test substance. There were no compound-related effects on organ
weight parameters in male mice, however, 350 ppm female mice had
elevated absolute and relative liver weights. The changes in liver
weight most likely represent enzyme induction associated with metabolism
of the test substance. 100 and 350 ppm male mice and 350 ppm female mice
had an increased incidence of pigment accumulation in the Kupffer cells.
Male mice exposed to 100 or 350 ppm and females exposed to 350 ppm
exhibited an increased incidence of individual hepatocellular necrosis,
and 350 ppm males had an increased incidence of hepatocellular
mice exposed to 350 ppm test substance had an increased incidence of
bilateral, diffuse retinal atrophy. Since there are a number of factors
known to modulate the development of this common lesion, the increased
incidence may be the result of an indirect effect stemming from the
compound-related changes in the liver.
mice, exposure to the test substance for 18 months did not produce an
oncogenic response in the liver or any other tissue of either sex at any
exposure concentration. In addition, there were no compound-related
effects on hepatic cell turnover in mice of either sex at any exposure
concentration. Therefore, the no-observable-adverse-effect level (NOAEL)
for oncogenicity was 350 ppm in mice.
NOAEL for toxicity for male mice is 25 ppm based on clinical signs of
toxicity and/or morphological changes at 100 and 350 ppm. The NOAEL for
female mice is 100 ppm based on clinical signs of toxicity and
morphological changes at 350 ppm.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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