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: 440-520-9 | CAS number: -
In the course of a GLP conform subacute toxicity study, the test substance was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 0, 50, 200 and 1000 mg/kg body weight/day for a period of 28 days according to the OECD guideline 407 (RCC Ltd, 2002). Administration of the test item did not induce mortalities, signs of treatment related toxicity or any other changes. A transient, minor decrease in locomotor activity in high dose animals is considered to be a not-treatment related effect. Thus, the NOAEL is considered to be 1000 mg/kg bw/day.
In a 90-day repeated dose toxicity test on an analogue substance (comparable to OECD TG 408, acc. to GLP) by oral gavage in male and female Sprague Dawley rats no toxicity occurred up to the limit dose of 1000 mg/kg bw/day ETH50. The NOAEL was determined to be 1000 mg/kg bw/day.
CHEMICAL ANALYSIS: The dosage forms stability, homogeneity and achieved concentrations were satisfactory.
When measured on day 2 (24 hours after dosing on Day 1) and on weeks 6 and 13 for groups 2, 3 and 4, which received the test item at 50, 250 and 1000 mg/kg/day, plasma levels of FAT 65'080 were not quantifiable for all animals at any time-point.
In this GLP conform subacute toxicity study, the test substance was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 0, 50, 200 and 1000 mg/kg body weight/day for a period of 28 days according to the OECD guideline 407 (RCC Ltd, 2002). The groups comprised 5 animals per sex which were sacrificed after 28 days of treatment. Additional 5 rats per sex and group were used at 0 and 1000 mg/kg. These animals were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Clinical signs, outside cage observation, food consumption and body weights were recorded periodically during pretest, the treatment and recovery periods. Functional observational battery, locomotor activity and grip strength were performed during week 4. At the end of the dosing and the treatment-free recovery period, blood samples were withdrawn for hematology and plasma chemistry analyses. Urine samples were collected for urinalyses. All animals were killed, necropsied and examined post mortem. Histological examinations were performed on organs and tissues from all control and high dose animals, and all gross lesions from all animals. All animals survived until scheduled necropsy. No test item-related clinical signs, no changes in hematology, urinalysis, food consumption or body weight and no effects on organ weight or any micro/macroscopic changes were noted during daily or weekly observations. Minor reduction in locomotor activity was noted in the first 15 min/1h in both sexes treated with 1000 mg/kg/day. Locomotor activity of the recovery groups was not conducted. Measurements of locomotor activity in rodents serve as preliminary tests to determine motor deficits or anxiety. The test is sensitive to motor dysfunction as well as for neuronal damages. A motor dysfunction or an effect of the substance on the nervous system is expected to cause a constant reduction in locomotor activity and to provoke correlating effects in other parts of the FOB. The reduction in locomotor activity was a transient short term effect, limited to the 1000 mg/kg bw group. A dose response relationship or correlating effects in grip strength or clinical signs were not observed. The change in locomotor activity of the high dose group is, therefore regarded as an unspecific, not-treatment related effect. Based on the results of this study, 1000 mg/kg/day was considered to be the no-observed-adverse-effect-level (NOAEL).
In the sub-chronic repeated dose toxicity study (with an analogue substance) under GLP (CIT 28341 TCR, 2005) three groups of 10 male and 10 female Sprague-Dawley rats were treated by daily oral gavage with non-micronized ETH50 as a suspension in the vehicle (0.5 % [w/v]carboxymethylcellulose in purified water), at dose-levels of 0, 50, 250 or 1000 mg/kg/day for 13 weeks. Six additional males and females were added to control and high-dose groups (0 and 1000 mg/kg bw/day) for a 4 -week post-treatment recovery period. Satellite groups of six males and six females were added to the test item-treated groups for toxicokinetic investigations. Satellite animals were discarded without further examination after the last blood sampling. All study animals were checked for mortality, clinical signs and detailed clinical observations were performed. Functional Observation Battery tests were performed and ody weight/ food consumption was recorded. Ophthalmology, hematological and blood biochemical investigations and urinalysis was performed. Plasma levels of the test item were determined on blood samples taken from satellite animals and T3, T4, TSH and sexual hormones (males: testosterone, females: estradiol and progesterone) levels were measured on blood samples taken. Estrous cycle stages of all principal females were determined from vaginal smears. Designated organs were weighed, macroscopic and histological examinations were performed on selected tissues from controls, high-dose group (0 and 1000 mg/kg bw/day) and on macroscopic lesions.
The oral administration of the test substance to rats up to and including 1000 mg/kg bw/day, followed by a 4-week recovery period, did not cause any biologically significant test substance related effects.
The only clinical sign with dose-related frequency was piloerection in males treated at 250 or 1000 mg/kg/day. This finding was infrequent (1/10 at mid-dose, 3/16 at high-dose) and had always disappeared by week 10. As it was not noted in females and not associated with other findings, this observation was considered to be most probably treatment-related but not to be an adverse effect. There was no treatment-related clinical sign in principal females or in satellite animals.
On week 13, low- and high-dose males had moderately lower white blood cell counts when compared to controls (up to -25%), due to significantly lower lymphocyte and monocyte counts. Yet there was a high inter-animal variability (2-fold among controls males) and there was no difference between the mid-dose and control groups. These changes were therefore considered not to be treatment-related. There was no significant WBC count alteration in females or at the end of the recovery period.
Overall, these effects were not considered to be of toxicological significance. Thus, 1000 mg/kg bw/day is considered to be the no-observed-adverse-effect-level (NOAEL) for ETH50 in rats of both sexes.
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) 1272/2008. Based on this data the substance does not need to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.
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