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: 215-304-0 | CAS number: 1320-51-0
The only information we have that is relevant to assessing the potential for hydroxyethyl urea to cause adverse effects on fertility comes from the OECD414 pre-natal development study where only the females are dosed and from the 90 day dermal study. In the OECD414 no adverse effects were seen in the parental females and in the 90 day dermal study no adverse effects were seen on the weights of the male and female reproductive organs or indication of any histopathological damage to them. When this is taken together with the general pattern of extremely low toxicity for hydroxyethyl urea, there is no scientific justification to carry out any further reproduction testing.
We have Klimisch I validity OECD414 pre-natal development study in rats by the dermal route. This study showed no adverse effect on the development of the foetuses even with parental females dosed at the 1000mg/kg bodyweight limit dose.
In the GLP and OECD guideline conform study, 25 female Sprague-Dawley rats per group were exposed dermally to 0 (RODI water), 100, 330 and 1000 mg/kg bw/day of hydroxyethyl urea (based on test material EXP 3982 (N-2 -hydroxyethylurea)) for approximately six hours daily from gestation day 6 through gestation day 19. Elizabethan collars were placed around the neck of each animal during the six-hour exposure period, the collars were then removed and the test site was wiped clean with gauze moistened with tap water. The dosing sites were clipped free of hair prior to the first application and when necessary thereafter. A collar check was performed a minimum of once daily during the six-hour exposure period. The animals were observed daily for clinical signs of toxicity. The test site was examined for erythema and oedema prior to dosing on gestation days 6, 9, 12, 15 and 19 and prior to scheduled euthanasia on gestation day 20. Individual body weights were recorded on gestation days 0 (from the supplier), 5, 6, 9, 12, 15, 19 and 20. Individual food consumption was recorded on gestation days 6, 9, 12, 15, 19 and 20. All females were euthanised by carbon dioxide inhalation on gestation day 20 and subjected to cesarean section. Foetuses were individually weighed, sexed and examined for external and visceral or skeletal abnormalities.
No mortality or clinical signs of toxicity were noted during the study. Mean food consumption of females in the 1000 mg/kg/day group was statistically lower than controls during gestation days 12-15 and 15-19 and throughout the overall treatment period (gestation days 6-19). However, there were no statistically significant differences in mean body weights or body weight gain between the control and test article-treated groups. Similarly, there were no statistically significant differences in gravid uterine weights, maternal body weight changes or corrected maternal body weight change between the control and test article-treated groups on gestation day 20. Maternal gross necropsy findings were generally unremarkable. There were no statistically significant differences between the control and test article-treated groups in the cesarean section parameters, including the mean number of corpora lutea, implantation sites, viable foetuses, early and late resorptions, pre- and post-implantation loss, foetal sex ratios and mean foetal body
weights. There were no statistically significant or toxicologically meaningful differences in the incidence of foetal malformations or developmental variations between the control and test article-treated groups.
Based on the results of this study, a dosage level of 1000 mg/kg/day (based on hydroxyethyl urea) was considered to be the no-observed-adverse-effect level (NOAEL) for maternal toxicity and developmental toxicity in this study following dermal administration of EXP3982 (N-2-hydroxyethylurea) to pregnant rats during the period of major organogenesis. Bsed on these results hydroxyethyl urea is not classified for developmental toxicity by CLP/GHS criteria as no effects were seen.
The available information concerning the potential for hydroxyethyl urea to cause adverse effects on fertility, other reproductive parameters and the survival and development of the foetus are from a dermal OECD414 pre-natal development study in rats and from the weights of the reproductive organs and their histopathological examination. These studies showed no adverse effects on any of the parameters even at the 1000mg/kg bodyweight limit dose. The lack of any adverse effects in the 90 day dermal study and the general lack of any toxic effect from hydroxyethyl urea taken with these results do not indicate any potential for adverse effect on reproduction or development of the foetus. While we have no data by the oral and dermal routes of exposure, neither of these are exposure routes of exposure for hydroxyethyl urea. The Epiwin model data predicts a high level of both oral and dermal absorption both in the region of 77-78% which justifies the use of the dermal NOAEL to calculate ORAL and inhalation long term DNELs.The fact than the DNELs will be based on a NOEL i.e. the lack of any effects at 1000mg/kg bodyweight which will be used as the NOAEL for the calculation will result in conservative DNELs. The use of DNELs based on the 90 day study will provide addition assessment factors than the use of DNELS based on the OECD414 NOAEL also of 1000mg/kg bodyweight resulting in the lower DNELs.
The available information concerning the potential for hydroxyethyl urea to cause adverse effects on fertility, other reproductive parameters and the survival and development of the foetus are from a dermal OECD414 pre-natal development study in rats and from the weights of the reproductive organs and their histopathological examination. These studies showed no adverse effects on any of the parameters even at the 1000mg/kg bodyweight limit dose. The Epiwin model data predicts a high level of dermal absorption in the region of 77-78% which justifies the use of the dermal route for these studies and their subsequent use for a classification decision.There were no adverse effects on reproductive parameters or development of the foetus; therefore there is no requirement to classify hydroxyethyl urea toxicity as toxic to reproduction according to the EU CLP (GHS) criteria.
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