Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
A GLP-study according to OECD guideline 410 in rabbits is available for phenoxypropanol
Effect on fertility: via oral route
Dose descriptor:
NOAEL
477.5 mg/kg bw/day
Additional information

In a 2-generation reproductive toxicity study in rats, phenoxypropanol was continuously administered with drinking water over two parental generations at concentrations of 0, 100, 1000 and 5000 ppm. Reproductive performance or fertility was not affected in F0 or F1 parental animals of either dose group. Estrous cycle, mating behavior, conception, gestation, parturition, lactation and weaning as well as sperm parameters, sexual organ weights, and gross and histopathological findings of these organs were similar between control and treated animals. Signs of general, systemic toxicity were noted in both parental generations (F0 and F1) in groups receiving 5000 ppm, but not in others. Toxicity was characterized by decreased water and food consumption, decreased body weight and body weight gain in parental F0 an F1 males and females. Pathology and histopathology did not reveal substance-related adverse effects in F0 and F1 parental animals. The clinical, gross and histopathological examinations in F0 and F1 parental animals from the low and intermediate dose groups did not yield any indication of systemic toxicity. Substance-related signs of developmental toxicity were seen in progeny of the high dose (5000 ppm) F0 and F1 parents in terms of reduced pup body weight and body weight gain. This is directly related to lower absolute weights of the thymus, spleen and brain in pups and delayed sexual maturation. Moreover, reproduction parameters of these animals were not adversely affected after gaining sexual maturity. This supports the view that delayed preputial separation and vaginal opening resulted from a general retardation of physical development. No signs of developmental toxicity were seen in pups from groups receiving medium or low doses (1000 or 100 ppm, respectively.). Under the conditions of this study, NOAELs were established as follows:

NOAEL for reproductive performance and fertility: 5000 ppm (about 477.5 mg PPh/kg body weight/day) for the F0 and F1 parents NOAEL for developmental toxicity: 1000 ppm (about 113.9 mg PPh/kg body weight/day) for the F1 and F2 progeny

NOAEL for general systemic toxicity: 1000 ppm (about 113.9 mg PPh/kg body weight/day) for the F0 and F1 parents

Thus, developmental toxicity was seen only at a dose which was also toxic to the parent animals. No sign of teratogenicity was seen at either dose in this study.


Short description of key information:
A GLP-study according to OECD guideline 416 - conducted in rats - is available for phenoxypropanol. The test material was administered via the drinking water.

Effects on developmental toxicity

Description of key information
GLP-studies according to OECD guideline 414 using oral gavage administration have been conducted with phenoxypropanol in rats and in rabbits.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
180 mg/kg bw/day
Additional information

In a teratology study in rabbits using oral gavage administration of phenoxypropanol, the administration of test substance to pregnant Himalayan rabbits during organogenesis induced overt maternal toxicity at 540 mg/kg body weight/day, but was not toxic to the does at 60 and 180 mg/kg body weight/day. Maternal toxicity at the highest dose level was substantiated by reduced food consumption, impairments in body weight gain and adverse clinical symptoms (e.g. apathy/lateral position). Signs of developmental toxicity occurred only at the highest dose level (540 mg/kg body weight/day) in the form of an increased occurrence of skeletal variations (predominantly accessory 13th rib(s)); however, no substance-induced teratogenic effects were observed up to and including the dose of 540 mg/kg body weight/day. At 60 and 180 mg/kg body weight/day no influence on the gestational parameters and no signs of developmental toxicity, especially no substance-induced indications of teratogenicity, were observed. For this prenatal toxicity study in Himalayan rabbits, the no observed adverse effect level (NOAEL) concerning maternal and developmental toxicity is 180 mg/kg body weight/day.

In a second teratology study in rats also using oral gavage administration of phenxoypropanol, dose-related overt signs of maternal toxicity were seen in animals receiving 640 or 160 mg/kg per day. Transient salivation, apathy and piloerection occurred in several high dose animals after gavage. Compared with control animals, significant changes in food consumption (-14%), body weight gain (-20%), corrected body weight gain (-43%) and carcass weight (-6%) was noted in the high dose animals. Gestational parameters were not affected. Less severe signs of toxicity were seen in the animals receiving 160 mg/kg per day. The effects on food intake (-6%) and body weight (BWC -16%; corrected BWC -18%) were less pronounced. Again, gestational parameters were not affected. No substance-related effects on dams were seen in animals receiving 40 mg/kg per day. Prenatal developmental toxicity was seen in fetuses from dams receiving 640 mg/kg per day in terms of significantly reduced fetal weight (-10%) and significantly increased occurrence of skeletal variations, due to higher rates of fetuses with incomplete ossification of sternebra. No substance-related effects were noted in fetuses from dams receiving 160 or 40 mg/kg per day. NOAEL for maternal toxicity was 40 mg/kg per day; NOAEL for prenatal developmental toxicity was 160 mg/kg per day. No substance-induced teratogenicity was seen up to 640 mg/kg per day. Thus prenatal toxicity was seen at a dose which was severely toxic to the dams. No teratogenic effects were noted at any dose.

The NOAELs for developmental toxicity were very similar in rats (160 mg/kg bw/d) and rabbits (180 mg/kg bw/d). The slight difference is likely due to the differences in the dose level selection between the 2 studies. In the rat study, the only developmental effects observed at the next higher dose level of 640 mg/kg bw/d were reduced fetal weight (-10%) and increased occurrence of skeletal variations. Similar effects were also observed in the rabbit study at the next higher dose level of 540 mg/kg bw/d indicating comparable sensitivity of the two species. Hence, the NOAEL from the rabbit study is taken as key value for this endpoint.

Toxicity to reproduction: other studies

Additional information

In a 28 -day dermally toxicity study in rabbits no toxicity to reproductive organs was evident based on organ weights, gross observation, or microscopic examination.

Justification for classification or non-classification

Phenoxypropanol did not produce any developmental effects in the absence of maternal toxicity in rats and rabbits. No effects on fertility were observed in a 2-generation study in rats. Hence, no classification for reproductive toxicity is required for phenoxypropanol.

Additional information

Categories Display