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EC number: 923-900-3 | CAS number: -
There are no studies available on reproductive toxicity/fertility of the substance. In rodents histopathological examinations in repeated dose toxicity studies of reproductive tissues are of high value and high sensitivity for evaluation of reproductive toxicity in males and females, as confirmed by literature*. Histopathological changes on the reproductive organs in repeated dose toxicity studies are indicative of effects on fertility. With this respect repeated dose toxicity studies should be considered sensitive and sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covered.
For the substance there is no evidence for treatment-related findings on reproductive organs or tissues on the basis of gross and histopathological investigations of reproductive organs performed in a subacute toxicity (28-day) study according to OECD 407 and thus classification on reproductive toxicity/fertility is not warranted.
(*BAuA Forschungsbericht 984, 2003, Mangelsdorf. et al., Reg. Tox. and Pharm.37, 2003, 356-369; Ulbrich & Palmer, J. Am. Coll. Toxicol. 14, 1995, 293-327; Janer et al., Reproductive Tox. 24, 2007, 103-113; Dent, Reg. Tox. and Pharm. 48, 2007, 241-258; Sanbuissho et al., J Tox. Sci. 34, 2009, Special Issue SP1-SP22)
A developmental toxicity/teratogenicity study according to OECD TG 414 was conducted with twenty-five inseminated female Wistar rats each treated daily orally by gavage with the test substance using paraffin oil as vehicle. Females were treated from day 6 to day 20 of gestation with dosages of 0 (vehicle control), 100, 300 and 1000 mg/kg bw. The fetuses were delivered by cesarean section on day 21 of gestation.
No substance related findings were noted in maternal animals up to and including the high dose level of 1000 mg/kg bw. The gestation rate, number of corpora lutea, postimplantation loss, litter size, number of fetuses, fetal sex distribution, placental weights and placental appearance were not affected by treatment up to and including 1000 mg/kg bw test substance. No compound-related fetal structural findings classified as malformations or variations were observed in this study at levels up to and including 1000 mg/kg bw.
The no-observed-adverse-effect levels (NOAELs) were determined both for maternal and developmental toxicity to be 1000 mg/kg bw.
REACH establishes that for substances manufactured or imported in quantities of 100 tonnes and more a screening for reproductive/developmental toxicity (OECD 421 or 422) and a developmental toxicity study (OECD 414) is the standard information requirement. In January 2009 the substance was allocated to the tonnage band >100 t/y and thus, a developmental toxicity study (OECD 414) was initiated. At that time the REACH requirements were interpreted such that for a substance in the >100 t/y band it would be an option to perform the definitive study (OECD 414) instead of the screening (OECD 421 or 422) together with a testing proposal for the definitive study (OECD 414). Because of the known limitations of the screening study (mainly as it will not lead to a final conclusion as needed under REACH in a vast majority of cases and therefore would lead to additional in vivo testing) and for reasons of animal welfare (to reduce the overall number of animals) as well as to cover potential regulatory needs outside Europe no such screening study was initiated, but the definitive developmental toxicity study (OECD 414). Only later, in September 2009 the ECHA fact sheet (ECHA-09-FS-05-EN) was published, which clarified that registration dossiers for substances >100 t/y were considered as technically complete if they would contain a testing proposal for a prenatal developmental toxicity study only. Therefore a developmental toxicity study was already available in 2010.
This developmental toxicity/ teratogenicity study according to OECD TG 414 was conducted with twenty-five inseminated female Wistar rats treated once daily with the test substance in paraffin oil administered by gavage. Females were treated from day 6 to day 20 of gestation with dosages of 0 (vehicle control), 100, 300 and 1000 mg/kg bw. The fetuses were delivered by cesarean section on day 21 of gestation.
No substance related findings were noted in maternal animals up to and including the highest dose of 1000 mg/kg bw. The gestation rate, number of corpora lutea, postimplantation loss, litter size, number of fetuses, fetal sex distribution, placental weights and placental appearance were not affected by the treatment. No compound-related fetal structural findings classified as malformations or variations were observed in this study up to and including 1000 mg/kg bw.
No classification required for toxicity to reproduction according to Regulation (EC) No 1272/2008, Annex I.
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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