Fatty acids, tall-oil, reaction products with ethanolamine, ethoxylated

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

As reported in literature (Mangelsdorf et al., 2003; Ulbrich and Palmer, 1995; Janer et al., 2007; Dent, 2007; Sanbuissho et al., 2009), histopathological examinations of reproductive tissues in repeated dose toxicity studies on rodents are of high value and high sensitivity for evaluation of reproductive toxicity in males and females. Thus, the available 28d study and two 90d studies that included comprehensive examinations of reproduction tissues and parameters indicate that the target substance is not toxic to reproduction. Furthermore, no evidence for reproduction toxicity was detected in two chronic studies conducted with two structural homologues (please refer to ch. 13 for read-across). The information above and the toxicokinetic profile, that indicates an efficient metabolism and excretion, support the conclusion that the target item is not toxic to reproduction organs.

Dent MP. 2007. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.Regul Toxicol Pharmacol.2007 Aug; 48(3):241-58. Epub 2007 Apr 12.

Janer G, Hakkert BC, Slob W, Vermeire T, Piersma AH. 2007.A retrospective analysis of the two-generation study: What is the added value of the second generation? Reprod Toxicol 24:97-102.

Mangelsdorf, I., Buschmann, J., Orthen, B., 2003.Some aspects relating to the evaluation of the effects of chemicals on male fertility. Regulatory Toxicology and Pharmacology 37, 356–369

Sanbuissho A, Yoshida M, Hisada S,et al., 2009. Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Toxicol Sci 2009.:SP1-22.

Ulbrich, B. and Palmer, A.K. (1995). Detection of effects on male reproduction: a literature survey. J. Am. College of Toxicology 14, 293–327

Short description of key information:
The target substance was subjected to an OECD 407 guideline study that included additional examinations of reproduction-relevant parameters (histopathological examinations of reproductive tissues, estrous cycle, sperm parameters). Up to the highest dose, no subsatnce-releated adverse effect was detected. Thus, the NOAEL of the study was determined to be 1000 mg/kg bw/d.
In two further studies (subchronic, dermal) with structural homologues (please refer to ch. 13 for read-across justification), sperm parameters and vaginal cytology were evaluated. The sperm parameters comprised sperm concentration, sperm motility, sperm count, spermatid heads per testis, and spermatid heads per gram of testis. The left cauda, epididymis, and testis were weighed. Furthermore, the estrous cycle length and relative frequency of estrous stage were determined. The evaluations gave no indication for adverse effects on fertility.

Justification for selection of Effect on fertility via oral route:
OECD and GLP compliant study with additional parameters to evaluate a potential toxicity to reproduction organs.

Effects on developmental toxicity

Description of key information

A structurally similar substance (please refer to ch. 13 for read-across) was not toxic to pregnant rats and did not reveal any embryotoxic or teratogenic potential at dose levels up to 1,000 mg/kg/d. Therefore, based on the read-across study, the target substance is not considered to be a developmental toxicant. 

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:

The information requirements for this tonnage band is sufficiently met with the available data.

Additional information

Developmental toxicity

A study was carried out to assess the effects of structurally similar substance amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl) on embryonic and foetal development in pregnant Sprague-Dawley CD rats following the procedures indicated by the OECD guideline 414 (Teratogenicity) and the EU Directives 87/302/EEC and 91/325/EEC. The test substance was administered to groups of 30 female rats orally by gavage at dose levels of 0, 100, 300 and 1,000 mg/kg/d, once daily from Day 6 to Day 15 of gestation inclusive. Control animals were dosed with the vehicle alone (arachidis oil, DAB 9). Clinical condition and reaction to treatment were recorded at least once daily. Body weights were reported on Day 0, 6, 16 and 20 of gestation. All surviving females were sacrificed on Day 20 of gestation and the foetuses were removed by caesarean section. At necropsy the females were examined macroscopically. Live foetuses were weighed, sexed and were examined for visceral and skeletal abnormalities.

No deaths or treatment-related changes in body weight gain and necropsy findings were observed in dams at any dose level. Treatment-related symptoms observed in all treatment groups were salivation and propulsion of the head. Additionally, the highest dose group showed severe salivation. Apart from the control (1 dead foetus) and the 100 mg/kg/day group (7 dead foetuses), all females had viable foetuses. Pre-implantation loss and mean numbers of resorptions were not affected by treatment. The figures of post-implantation loss, embryonic deaths and total foetuses showed some deviations which were considered to be non-treatment-related. Mean foetal placental and uterus weights were not affected by the treatment. Foetal sex ratio was comparable in all groups. No treatment-related foetal abnormalities were found at necropsy. The examined foetuses showed no treatment-related visceral and skeletal abnormalities/variations. One foetus in 300 mg/kg/d group showed a stump tail and missing vertebrae coccigycae. Further, the figures of skeletal ossifications showed some deviations in the two highest dose groups. However, all these effects were assessed to be non-treatment-related. Based on the results, 'amides, C12-18(even-numbered) and C18(unsatd.), N,N-bis(hydroxyethyl)' was found not to be cumulative toxic to pregnant rats and did not reveal any embryotoxic or teratogenic potential to Sprague-Dawley CD rats at dose levels up to 1,000 mg/kg bw/d.

Justification for classification or non-classification

The available data suggests that the target substance is not a reproductive toxicant with regard to fertility or developmental effects. Therefore no classification is required according to EC criteria (67/548/EEC) and CLP criteria (EC 1272/2008).