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EC number: 606-330-7 | CAS number: 195008-76-5
Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl- was administered daily in corn oil via gavage to groups of 10 male and 10 female Wistar rats at dose levels of 100, 300, and 1000mg/kg. Because of the premature death of 2 female animals, the high dose was reduced from 1000 to 600 mg/kg bw/d from study day 19 onwards. The duration of treatment covered 36 days in males and 51 days in females, including premating, mating, gestation and 4 days of lactation.
After 2 weeks of premating treatment the F0 animals were mated to produce F1 generation pups. Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. A detailed clinical observation (DCO) was performed in all animals before initial test substance administration and at weekly intervals thereafter. Food consumption of the F0 parents was determined once weekly during premating. For the dams food consumption was determined for gestation days 0-7, 7-14, 14-20 and lactation days 1-4. Body weights of F0 parents were determined once a week, in males throughout the study and in females during premating and mating. During gestation and lactation period, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, after the day of parturition (postnatal day [PND] 0) and on PND 4. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed under isoflurane anesthesia with CO2 and examined macroscopically for external and visceral findings. Towards the end of the administration period a functional observational battery was performed and motor activity was measured in 5 animals per sex and test group. Clinicochemical and hematological examinations as well as urinalyses were also performed towards the end of the administration period in 5 animals per sex and test group. All F0 parental animals were sacrificed by decapitation, under isoflurane anesthesia, and were assessed by gross pathology. Weights of selected organs were recorded and a histopathological examination was performed.
Of the high dose animals, one male and one female were found dead, and one female was sacrificed in moribund condition. Piloerection, smeared fur, respiratory sounds, poor general state, hunched posture, and semiclosed eyelids were observed in single animals of this group at different time points. Pathology revealed erosion/ulcer in the forestomach of all male and 9/10 female high dose animals, mild to severe diffuse or focal hyperplasia with hyperkeratosis in the forestomach of all animals, and mild to severe submucosal edema in the forestomach of 8 male and 3 female animals. Animals receiving 300mg/kg b.w. showed comparable signs of local irritation in the forestomach, though the incidence was clearly reduced. No clinical signs were noted in this group and in low dose animals, which also showed no local irritation in the stomach. Reproductive performance was unaffected in all groups. No deviations from control animals were observed in the pubs from all groups. Thus the NOAEL for fertility and developmental toxicity was set to 600mg/kg b.w. Though the clinical signs and deaths of high dose animals are most likely secondary to the severe irritation in the stomach, systemic toxicity cannot be completely excluded. Following the precautionary principle, the NOAEL for systemic effects was set to 300mg/kg b.w., and the NOAEL for local irritation was set to 100mg/kg.
combined rep. dose / dev. screening study, rat (BASF 2013, GLP, OECD422): NOAEL (dev.) = 600mg/kg (highest dose)read across substances:Dibutylamine, hydrochlorid salt (6287-40-7): teratogenicity, rat (BASF 2010, GLP, OECD 414): NOAEL (dev.) = 150mg/kg (highest dose)TMPeoTA (28961-43-5): teratogenicity, rat (Cytec 1984, GLP, OECD 414): NOAEL (dev.) = 1000mg/kg (highest dose)
As already discussed for effects on fertility, Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl- was tested in an OECD 422 study, in which viability and macroscopic abnormalities of the pubs are also assessed. No difference to control pubs were observed in this study. Though this study does not fulfill all requirements to completely exclude developmental defects, it supports the negative results obtained with the two components of the test substance: Propylidynetrimethanol, ethoxylated, esters with acrylic acid (TMPeoTA, CAS 28961 -43 -5) and 1-Butanamine, N-butyl- (tested as the hydrochloric salt, CAS 6287 -40 -7). For all three substances, the primary effect in maternal animals is local irritation in the stomach. Most likely, all further systemic effects like weight loss and poor general state are secondary to the irritant properties. No specific target organ toxicity was observed in all three cases.
TMPeoTA and Dibutylamine-HCl were tested according to (or similar to ) the OECD 414 guideline for prenatal developmental toxicity. 30 Spraque Dawley female rats were treated orally with 1000mg/kg TMPeoTA in corn oil from gestation days 6 -15. The animals were sacrificed on gestation day 20, and uteri and ovaries were examined for corpora lutea, implantations, early resorptions, and late resorptions. All fetuses were examined externally. Sex ratio and viability were determined. Half of the fetuses were subjected to soft tissue examination, while the other half was examined for sceletal abnormalities. A significant decrease in body weight of the dams was observed from gestation days 6 -16. Clinical signs included salivation, urogenital matting and hair loss from various body surfaces. No embryotoxicity or teratogenicity was noted.
CAS 6287 -40 -7 was administered by gavage to 25 pregnant female Wistar rats at concentrations of 15, 50, and 150 mg/kg in water from gestation days 6 -19. The animals were sacrificed on gestation day 20, and the gravid uterus weight, number of corpora lutea, number of implantation sites, early resorptions, late resorptions, the number of dead fetuses, and the sex of all fetuses were determined. All fetuses were examined externally, and subjected to soft tissue and sceletal examinations. There were no test substance-related effects on the dams concerning mortality, food consumption, gross and corrected (net) body weights, gestational parameters, uterine and placental weights, as well as necropsy observations up to and including a dose of 150 mg/kg bw/day. Some mid- and high-dose dams showed transient salivation for a few minutes immediately after each treatment, which was likely to be induced by the unpleasant taste of the test substance or by local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity. Salivation was not observed after treatment with the low doses. Body weight gain of the high-dose rats was significantly reduced (by 63%) at initiation of treatment (GD 6-8) but recovered afterwards. The increase of the red blood cell counts, the hemoglobin as well as the hematocrit values in the dams on GD 20 beginning in the 50 mg/kg bw/d dose group was an indication of hemo-concentration, most probably because of stress. This assumption was confirmed by the increase of the total white blood cell counts, which was due to higher lymphocyte counts, in the rats of the 150 mg/kg bw/d dose group. Correspondingly, the increase of the urea as well as of the cholesterol values in the dams beginning in the 50 mg/kg bw/d dose group can be interpreted as a consequence of stress accompanied by an increased protein metabolism. Additionally, the latter effect can be partly explained by an increased bone metabolism, which was also expressed by increased inorganic phosphate and calcium blood levels in the rats beginning in the 50 mg/kg bw/d dose group. A slight affection of the liver cells in the dams of the 150 mg/kg bw/d dose group was indicated by the increase of the ALT activity. Fetal examinations revealed no influence of the test compound on sex distribution of the fetuses, fetal body weights, and on fetal morphological structures.
No effects on fertility were observed in an OECD 422 study using Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl-. In this study, also no difference in pubs from control and treated animals were noted. In addition, one study each for prenatal developmental toxicity exists for the two components of the reaction mass, CAS 28961 -43 -5 and 6287 -40 -7. No treatment related effects on embryotoxicity or fetal malformations were found in these studies. Considering the results from all three studies, Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl- is not expected to cause developmental toxicity, teratogenicity or affect fertility. Therefore, it does not require classification according to 67/548/EEC or CLP/EU-GHS concerning reproductive toxicity.
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