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: 701-122-3 | CAS number: 106185-75-5
Homogeneity was confirmed for the test substance in Rat and Mouse No. 1 maintenance diet formulations at nominal concentrations of 100 ppm and 24000 ppm. Stability was confirmed at ambient storage for up to one day and frozen storage for 16 days for 100 ppm, at ambient storage for up to one day and frozen storage for 22 days for 500 ppm and at ambient storage for up to 8 days and frozen storage for 22 days for 24000 ppm.
The mean concentrations of the test substance in test formulations analysed for the study was within +10 %/-15 % of nominal concentrations, confirming accurate formulation. The percent difference from mean remained within 3 % confirming the precision of the analysis.
In a repeated dose toxicity study performed in accordance with OECD test guideline No. 408 and in compliance with GLP, test substance 2-ETHYL-4 -(2,2,3- TRIMETHYLCYCLOPENT- 3-EN-1-YL) BUT-(2E)-EN-1-OL was administered orally via the diet to groups of Crl:CD(SD) rats (10/sex/dose) at doses of 1500, 5000 or 15000 ppm for 13 weeks. A similarly constituted Control group received untreated diet, with vehicle (corn oil) only, throughout the treatment period. A further five male and five female rats were assigned to each of the control and high dose groups. These animals were treated for 13 weeks, followed by a four week period without treatment to assess the potential for any treatment-related change to recover. During the study, assessment of clinical condition, detailed physical and arena observations, sensory reactivity, grip strength, motor activity, body weight, food consumption, water consumption (visual observations), ophthalmoscopy, haematology, coagulation, blood chemistry, organ weights, macropathology and histopathology investigations were undertaken.
The overall achieved doses during Weeks 1-13 at 1500, 5000 and 15000 ppm were 100, 330 and 981 mg/kg bw/day for males and 109, 362 and 1109 mg/kg bw/day for females, respectively.
There were no premature deaths and no test article-related signs observed during the detailed physical examination and arena observations.
Sensory reactivity observations, grip strength, motor activity scores and ophthalmoscopy assessments for all groups of animals during Week 12 were unaffected by treatment.
Mean body weight gain of males and females given 15000 ppm was generally lower than Control throughout the treatment period (64% and 61% of Controls for males and females, respectively), with the most pronounced effects occurring in Week 1. Males given 5000 ppm showed statistically significant low mean body weight gain during Weeks 1-2 of treatment but thereafter were essentially similar to Control. Following the replacement of treated diet by untreated diet (with vehicle), the mean body weight gain of males and females previously given 15000 ppm was statistically significantly higher than Control (at least 200% of Control) over the 4-week recovery period. The mean body weight gain of females given 5000 ppm and of males and females given 1500 ppm was unaffected by treatment.
The mean food intake of animals given 15000 ppm was markedly lower than Control in Week 1 of treatment; thereafter, a clear increase in food consumption was apparent although weekly food intake remained lower than Control throughout the treatment period (overall food intake was 68 % and 73 % of Control for males and females, respectively). After replacement of the treated diet by untreated diet (with vehicle), animals in the 15000 ppm group showed a marked increase in food consumption.
Reduced food consumption, with associated reductions in body weight gain was thus evident in the 15000 ppm group, however this was deemed attributable to the treated diet being slightly unpalatable due to the class and high concentration of the test article, but not adverse as there was no evidence of primary toxicity.
Analysis of haematological parameters during Week 13 of treatment revealed lower than Control erythrocyte and haemoglobin concentrations and haematocrit in males and females given 15000 ppm, associated with a minor increase in red cell distribution width, and a slight decrease in mean cell haemoglobin concentration in females. All groups of treated males showed shorter than Control prothrombin times, with some evidence of a dose-related trend. Conversely, all groups of treated females showed shorter than Control activated partial thromboplastin times. All these differences were within 95 % confidence limits of the Historical Control Data range and were no longer evident 4 weeks after the cessation of dosing.
During Week 13, biochemical analysis of plasma revealed a non-dose-dependent decrease in urea, blood urea nitrogen and creatinine concentrations in all groups of treated males and females when compared to Controls. In addition, cholesterol concentrations were slightly high in males and females given 15000 ppm, changes in glucose concentrations were apparent in 15000 ppm group (slightly low in males and slightly high in females), alkaline phosphatase, albumin concentrations and albumin/globulin ratio were slightly high in males given 15000 ppm and aspartate amino-transferase concentrations were slightly low in females given 15000 ppm. All these differences were within 95% confidence limits of the Historical Control Data range and were no longer evident after 4 weeks off-dose.
The analysis of organ weights following 13 weeks of treatment indicated dose-dependent and statistically significantly higher than Control body weight-adjusted liver weight in all groups of treated males and in females given 5000 or 15000 ppm. Body weight-adjusted kidney weights were higher than Control in females given 15000 ppm, and body weight-adjusted uterus and cervix weights were slightly low in females given 5000 or 15000 ppm. Following 4 weeks of recovery, body weight-adjusted liver weights in males previously given 15000 ppm remained slightly higher than Control, although the magnitude of the difference was lower than that recorded at the end of the treatment period. In females previously given 15000 ppm, body weight-adjusted kidney weights remained higher than Control.
Plasma biochemistry revealed several slight changes in composition which were indicative of adaptations of metabolism/excretion in the liver and kidneys, and were accompanied by increases in liver and kidney weight. In the absence of any evidence of degenerative or functional change in the liver and kidneys during histopathological evaluation, the slight disturbances of biochemical parameters were considered not to be adverse.
There were no macroscopic abnormalities detected at scheduled termination after 13 weeks of treatment or after 4 weeks of recovery that were attributable to treatment.
Histopathological evaluation of the retained tissues revealed limited changes in the adrenal glands and thymus. Non-adverse minimal diffuse hypertrophy of the zona glomerulosa in the adrenal glands was seen in females given 5000 or 15000 ppm, and in one male given 15000 ppm. Full recovery was apparent after the four week recovery period. In addition, a minimal to slight increase in the incidence of tingible body macrophages was seen in the thymic cortex of animals in all treated groups. This change was considered to be secondary and stress-related and was no longer apparent after the 4-week recovery period.
It was concluded that dietary administration of the test item to Crl:CD(SD) rats at dietary inclusion levels of 1500, 5000 or 15000 ppm for 13 weeks provied clearevidence of systemic exposure but no effects which were deeme to be adverse.
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