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EC number: 686-241-8 | CAS number: 81058-27-7
Repeated dose toxicity - oral: In a combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test performed according to the OECD Guideline 422 and US EPA OPPTS 870.3650, no adverse parental effects were observed up to the highest dose level tested (750 mg/kg) (van Otterdijk, 2018). The following parental NOAEL was derived 750 mg/kg bw/day.
Repeated toxicity: oral
A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed in rats, in which male and female rats were exposed to 80, 250, 750 mg/kg bw/ day via gavage (OECD 422, Van Otterdijk, 2018). The vehicle used was propylene glycol and the test solutions were prepared daily and administered within 6 hours after preparation.
No adverse parental effects were observed up to the highest dose level tested (750 mg/kg).
There were no test item-related premature decedents in the study. However, one female (no. 61 dosed at 250 mg/kg/day) was sacrificed after 40 days of treatment. The animal had a vaginal prolapse with subsequently dilation of the uterus horns and serosal inflammation in the uterus at microscopy. An elongated activated partial thromboplastin time was recorded for females at 750 mg/kg. However, the mean remained within the normal range for rats of this age and strain, and there were no concurrent changes in other (clotting) parameters in this study. Therefore, this change was not considered to be adverse.
No treatment-related changes were noted in any of the other parental parameters investigated in this study (i.e. clinical appearance, functional observations, body weight, food consumption, clinical biochemistry investigations, macroscopic examination, organ weights, and microscopic examination).
In contrast to the range finding study (Test Facility Study no. 513676) where intermittently occurring clinical signs were observed at 500 and 1000 mg/kg including hunched posture, uncoordinated movements and/or piloerection, no such clinical signs were recorded for animals in the main study at 750 mg/kg. This may be related to the time point on which these signs were observed in the main study (i.e. shortly after dosing). Although no clear peak effect of occurrence of clinical signs were noted in the range finding study for the 500 and 1000 mg/kg dose levels combined, clinical signs recorded at 500 mg/kg were noted at 1-hour post-dose.
Based on the abovementioned considerations, the NOAEL was considered to be 750 mg/kg bw/day (nominal dose received).
Repeated toxicity: inhalation/dermal
A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation or dermal route of exposure.
Annex IX testing
A testing proposal for a repeated dose 90 -day oral toxicity study in rats is included for this substance .
As no effects are observed in the oral OECD 422 study (Van Otterdijk, 2018) up to 750 mg/kg/d, the substance doesn't meet the criteria for classification as STOT RE according to EU CLP.
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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