Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 239-556-6 | CAS number: 15520-10-2
The test material was administered by daily oral gavage to male and female Wistar rats at dose levels of 0, 50, 150 and 500 mg/kg/day. The males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 31 days). The females were exposed for 2 weeks prior to mating, during mating, during post-coitum, and at least 3 days of lactation (for 42 to 45 days). Formulation analysis showed that the formulations were prepared accurately, were homogeneous and were stable for at least 5 hours at room temperature.
No treatment related mortality occurred during the study period.
Slight to moderate salivation was noted in all males and females treated at 500 mg/kg. Furthermore, incidentally rales were noted in two males at 500 mg/kg and piloerection was noted in one female at 500 mg/kg at the end of treatment.
Yellow discolouration of the urine was noted in all animals of Groups 2, 3 and 4 in a dose dependant manner. This could be due to excretion of the test compound or a metabolite in the urine. Without corroborative findings for clinical biochemistry parameters and as no macroscopic or microscopic abnormalities of the kidneys were observed, this finding was not considered toxicological relevant.
At 500 mg/kg, reduced body weight gain was noted in males during the treatment period and in females on Days 14 to 20 post-coitum and during lactation (not always statistically significant). Furthermore, at 500 mg/kg food consumption before or after allowance for body weight was reduced during lactation in females (statistically not significant).
Hearing ability, pupillary reflex, static righting reflex and grip strength were normal in all animals, The motor activity test showed an increase in activity at the low sensor for females at 500 mg/kg, which might be due to hyperactivity of the dam and/or pups.
At 500 mg/kg, a treatment related decrease in eosinophils was noted in males and females. Furthermore, treatment related effects were noted in clinical biochemistry (mainly in males). These findings comprised high alanine aminotransferase, aspartate aminotransferase activities (also noted in females at 500 mg/kg) and alkaline phosphatase activities and high cholesterol levels. Cholesterol levels were also increased in males treated at 150 mg/kg, but to a lesser extent. These findings at 500 mg/kg correlated with the macroscopic or microscopic effects on the liver, e.g. pale discolouration, increased liver/body weight ratios and hepatocellular vacuolation of the liver at a minimal or slight degree. In addition, calcium levels were increased in males and females at 500 mg/kg. Besides microscopic changes in the liver, minor treatment related morphological alterations were noted in the lungs and adrenal glands: In the lungs, alveolar macrophage foci were increased in incidence and severity to moderate in females at 500 mg/kg. In the same organ lymphocytic alveolar inflammation was slightly increased in incidence in males and in incidence and severity to moderate in females. These findings correlated with the grey-white foci observed in females at 500 mg/kg. In the adrenal glands of males vacuolation in the zona fasiculata at minor degrees of severity was sbightly increased in incidence at 500 mg/kg which was not statistically significant. However there was a positive trend. The findings in liver, lung and adrenal glands were chiefly minor in nature and may be regarded as either slight increases in spontaneously occurring conditions or adaptive. As such they were considered to be indicators of slight toxicity to the test-item.
The organ weight changes in thymus and kidney correlated with the microscopic findings in these organs, e.g. atrophy and basophilia respectively. No corroborative findings were noted for the changes in weight of the heart, epididymides and brain. These changes were mild in nature and in absence of corroborative findings or a clear dose response relationship, the toxicological relevance of these changes remains unclear.
Based on these findings, the No Observed Adverse Effect Level (NOAEL) of this study was established at 150 mg/kg body weight/day.
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again