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EC number: 482-160-5
CAS number: 130786-09-3
The study was performed according the requirements
of OECD TG 407, EU method B.7 and US EPA OPPTS 870.3050 guidelines under
GLP conditions. Following a previously conducted 5-day sighting study,
the systemic toxic potential of the test item was assessed orally in a
28 day oral gavage study in Wistar: HannRcc: WIST(SPF) rats. Three
groups, each comprising five male and five female rats, received test
item at doses of 60, 200 or 600 mg/kg/day. A control group of five males
and five females was dosed with vehicle alone (Polyethylene Glycol).
Further satellite groups of 0 (control) and 600 mg/kg bw/day were
similarly treated for 28 days and then allowed a 14 day recovery period.
Chemical analyses of formulations were conducted once during the study
to assess accuracy, homogeneity and stability over 2 hours at room
temperature or 7 days under refrigeration. Formulation analyses
confirmed that formulations of test substance in polyethylene glycol
were prepared accurately and homogenously and were stable. Application
formulations investigated during the study were found to comprise test
item in the range of 93.2% to 110.4%. Clinical signs, food consumption
and body weights were recorded periodically during acclimatization,
treatment and recovery period. During week 4 of the treatment period, a
functional observational battery including measurement of grip strength
and locomotor activity was performed. No test item-related mortalities
were noted during treatment or recovery period. No adverse findings were
noted during daily clinical observations and no findings were noted
during weekly detailed behavioural observations at any dose level
tested. There were not changes in mean grip strength or mean locomotor
activity values for test item treated animals compared to controls.
Increased absolute and relative food consumption was noted in animals at
600 mg/kg/day (group 4) during treatment or recovery period. These
findings were considered to correlate with slightly decreased mean
absolute and relative body weights in high dose animals during treatment
period or at the beginning of recovery period in a compensating manner.
Test item-related decreased body weights were noted in both sexes at 600
mg/kg/day. Absolute and relative body weights caught up during recovery
period. The findings were therefore considered to be not adverse.
Hematological changes in the red blood cell parameters like MCV, MCHC,
HDW and reticulocytes were considered to be indicative for an anemic,
most likely hemolytic, occurrence during the treatment period. Elevated
relative and absolute reticulocytes along with elevated H-reticulocytes
were considered to clearly reflect a compensatory response. Changes in
hematology and biochemistry parameters were considered to be test
item-related, but of non-adverse character and reversible. Test
item-related non-adverse findings noted in animals treated with 60, 200
and 600 mg/kg/day were elevated absolute and relative liver weights
(males and females group 2, 3 and 4), elevated absolute kidney weights
(males and females group 2, 3 and 4) and elevated relative kidney
weights (males and females group 3 and 4, females group 2). Slightly
increased liver and kidneys to body weight ratios in females after
recovery period were markedly reduced compared to values of high dose
females at week 4 and also comparable to control values at week 4 and
therefore considered to be in general reversible. Test item-related
non-adverse findings noted in males treated with 200 and 600 mg/kg/day
were enlarged liver (1/5 males group 3 and 1/5 males group 4). Since
this finding was not noted after recovery period, it was considered to
be not adverse. Test item-related non-adverse findings noted in animals
treated with 200 and 600 mg/kg/day were centrilobular hypertrophy in the
liver (minimal or slight), increased hematopoiesis in the spleen
(minimal, slight or moderate), and tubular hypertrophy in the kidneys
(minimal or slight). Incidence and severity grades showed a
dose-dependent distribution, but were fully reversible during recovery
period. It was considered that all effects observed were non-adverse,
adaptive and/or were fully reversible at up to 600 mg/kg bw/day. Under
the conditions of this study, the No-Observed-Adverse-Effect-Level
(NOAEL) was regarded to be 600 mg/kg/day for males/females.
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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