Fatty acids, tall-oil, ethoxylated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, the oral administration by gavage of the test substance to Wistar rats revealed no adverse signs of toxicity in male and female animals at a dose level of 1000 mg/kg bw/d. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d for male and female Wistar rats. The NOAEL for reproductive performance and fertility was set to 1000 mg/kg bw/d for male and female Wistar rats.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP and guideline compliant study.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The test substance was given daily as a suspension to groups of 10 male and 10 female Wistar rats (F0 animals) by gavage at dose levels of 0 mg/kg body weight/day (mg/kg bw/d; test group 0), 100 mg/kg bw/d (test group 1), 300 mg/kg bw/d (test group 2) and 1000 mg/kg bw/d (test group 3) in accordance with OECD guideline 422 (BASF SE, 2018). Deionized water served as vehicle, control animals were dosed daily with the vehicle only. During the first week of application deionized water containing 0.5 % sodium carboxymethyl cellulose was used as vehicle. For practical reasons, the carrier was changed to deionized water without 0.5 % sodium carboxymethyl cellulose. The duration of treatment covered a 2-week premating period and mating in both sexes (mating pairs were from the same test group) as well as entire gestation and lactation period in females up to one day prior to the day of schedule sacrifice of the animals.

The parents' and the pups' state of health was checked each day, and parental animals were examined for their mating and reproductive performances. F0 animals were mated for a maximum of two weeks after the beginning of treatment to produce a litter (F1 generation pups). As soon as sperm was detected in the vaginal smear, mating was discontinued. F0 animals were examined for their reproductive performance including determinations of the number of implantations and the calculation of the postimplantation loss in all F0 females. A detailed clinical observation (DCO) was performed in all animals before initial test substance administration and, as a rule, thereafter at weekly intervals. Food consumption of the F0 parents was determined regularly once weekly before and after the mating period, as well as in dams during gestation days 7,14 and 20 and lactation days 4, 7, 10 and 13. In general, the body weights of F0 animals were determined once a week. However, during gestation and lactation, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, and on postnatal days (PND) 0, 4, 7, 10 and 13. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PNDs 1, 4, 7 and on PND 13 and their viability was recorded. On day 1 after birth the anogenital distance (AGD) was determined on all live male, female and uncertain pups. On PND 4, the individual litters were standardized in such a way that, whenever possible, each litter contains 4 male and 4 female pups (as a rule, the first 4 surviving pups/sex in each litter were taken for further rearing). On PND 13, all male F1 pups were examined for retention of nipples/areolae. The number of nipples/areolae anlagen were counted. At necropsy on PNDs 4 and 13, all pups were sacrificed with CO2 under isoflurane anesthesia and examined macroscopically for external and visceral findings. Blood samples were taken from all surplus pups or 2 preferably female pups per litter at PND 4 as well as one male and one female pup per litter at PND 13 by decapitation under isoflurane anesthesia. Additionally, blood samples from all dams at PND 14 and all males at termination were taken by puncturing the retrobulbar venous plexus under isoflurane anesthesia. Thyroid glands/parathyroid glands were fixed in neutral buffered 4% formaldehyde solution and transferred to the Laboratory Pathology for possible further processing. Towards the end of the administration period a functional observational battery was performed and motor activity was measured in 5 parental animals per sex and test group. Clinico-chemical and hematological examinations were performed in 5 parental animals per sex and group towards the end of the administration period. 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.

The various analyses confirmed

- the stability of the test-substance preparations for a period of 4 days at room temperature,

- the homogeneous distribution of the test substance in the vehicle,

- the correctness of the prepared concentrations.

The following test substance-related, relevant findings were noted:

Test group 3: 1000 mg/kg bw/d

F0 PARENTAL ANIMALS

Clinical Examination, Reproductive Performance, Clinical Pathology and Pathology

- No treatment-related, adverse effects were observed.

F1 PUPS

Clinical Examinations/ Gross Findings

- No treatment-related, adverse effects were observed.

Test group 2: 300 mg/kg bw/d

F0 PARENTAL ANIMALS

Clinical Examination, Reproductive Performance, Clinical Pathology and Pathology

- No treatment-related, adverse effects were observed.

F1 PUPS

Clinical Examinations/ Gross Findings

- No treatment-related, adverse effects were observed.

Test group 1: 100 mg/kg bw/d

F0 PARENTAL ANIMALS

Clinical Examination, Reproductive Performance, Clinical Pathology and Pathology

- No treatment-related, adverse effects were observed.

F1 PUPS

Clinical Examinations/ Gross Findings

- No treatment-related, adverse effects were observed.

Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, the oral administration by gavage of the test substance to Wistar rats revealed no adverse signs of toxicity in male and female animals at a dose level of 1000 mg/kg bw/d. Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 1000 mg/kg bw/d for male and female Wistar rats. The NOAEL for reproductive performance and fertility was set to 1000 mg/kg bw/d for male and female Wistar rats. Thus, the NOAEL for developmental toxicity was 1000 mg/kg bw/d.

Effects on developmental toxicity

Description of key information

Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, the oral administration by gavage of the substance to Wistar rats revealed no adverse signs of toxicity in the F1 generation of male and female animals at dose levels up to 1000 mg/kg bw/d. Thus, the NOAEL for developmental toxicity was 1000 mg/kg bw/d.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP and guideline compliant study.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Please refer to "Additional Information" provided under Fertility section.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as reproductive and developmental toxicant under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.