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: 923-900-3 | CAS number: -
A subacute oral toxicity study according to OECD TG 407 was conducted with the test item formulated in paraffin oil and administered by gavage to 5 male and 5 female Wistar rats per dose group. Doses were 0 (vehicle control), 100, 300 and 1000 mg/kg bw per day.
At clinical observations no test substance-related findings were noted. The functional observational battery did not reveal any evidence for a treatment-related effect. At motor/locomotor activity measurements the values were highest for the females of 1000 mg/kg but without statistical significance or correlations to other investigations no adverse effect was concluded. Body weight development as well as food and water intake was not affected by the treatment. Hematological investigation gave no evidence for test substance-related effects.
At necropsy distinct lobulation of the liver was found in males beginning at 100 mg/kg. At histopathology hypertrophy of centrilobular hepatocytes was observed in 3/5 males at 1000 mg/kg up to a slight degree. Correlation to liver lobulation observed at necropsy was only found in one 1000 mg/kg male. It was concluded that liver hypertrophy might indicate a non-adverse adaptive effect.
Thyroidal follicular cell hypertrophy with colloidal decrease was raised in females at 300 mg/kg by incidence and at 1000 mg/kg also by severity. Only a marginal increase could be found in males at 1000 mg/kg. Determination of TSH-concentration in peripheral blood showed in females highest values at 300 and 1000 mg/kg. Although there might be a slight correlation to the histopathological findings the changes observed are not regarded to be of toxicological relevance. It was concluded that thyroid hypertrophy might indicate a non-adverse adaptive effect. It is well known that there are species differences in thyroid system physiology between rodents and humans with the rat being especially sensitive to secondary responses of the thyroid system to liver enzyme induction (thyroid hormone imbalance).
The mesenterial lymph node showed foamy macrophage aggregates of minimal to moderate degree in all males and females at 1000 mg/kg and in one female at 300 mg/kg. A PAS stain detecting carbohydrate macromolecules was minimally to slightly positive in these areas. Macrophage aggregates in the mesenterial lymph node reflect a test substance-related effect, which might be attributed to intestinal resorption of the test article. No such findings were detected in distal lymph nodes (popliteal, mandibular). Gross and histopathological examinations of the intestine were unobtrusive.
Determination of organ weights at necropsy gave no evidence for treatment-related effects in males and females up to 1000 mg/kg. Gross and histopathological investigation into the other organs and tissues gave no evidence for treatment-related findings.
Therefore the no-observed-adverse-effect level (NOAEL) was 300 mg/kg body weight in males and 100 mg/kg body weight in females based on effects in mesenterial lymph nodes.
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