2-(4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(3-((2-ethylhexyl)oxy)-2-hydroxypropoxy)phenol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

A GLP-compliant study with structural analogue of the test item in Wistar rats according to OECD 414 excists. The test substance was administered as an oily solution to groups of 25 time-mated female rats by gavage at doses of 60, 200, 300 and 600 mg/kg bw/day on gestation days (GD) 6 through 19. Under the conditions of this prenatal developmental toxicity study, the oral administration to pregnant rats from implantation to one day prior to the expected day of parturition (GD 6-19) at a high-dose level of 600 mg/kg bw/day caused evidence of maternal toxicity, such as reduced gross and corrected (net) body weight gain. In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 300 mg/kg bw/d. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 600 mg/kg bw/d, the highest tested dose.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the attached read-across-justification

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

Dose descriptor:

NOAEL

Effect level:

600 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: abscence of adverse effects for the tested doses

Abnormalities:

no effects observed

Developmental effects observed:

no

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

600 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP-compliant OECD guideline study without deviations

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

For the assessment of the developmental toxicity of the test substance an OECD guideline study according to OECD 414 with a structural analogue of the test item was used for a read across approach due to a lack of data for this specific toxicological endpoint. This read across hypothesis is supported by comparable structural characteristics as well as physico-chemical properties and a similar toxicological behavior of the target and source substance. Adequate, reliable and available scientific information indicate that the target and source substance have similar toxicological profiles and that data for the source substance are reliable to predict the toxicity of the target substance. Therefore, the determined NOAEL for maternal toxicity of 300 mg/kg bw/d and NOAEL for prenatal developmental toxicity of 600 mg/kg bw/d for the source substance can be transfered to the toxicity profile of the test substance.

Details regarding the study:

In a prenatal developmental toxicity study the structural analogue was administered to pregnant Wistar rats daily by gavage from implantation to one day prior to the expected day of parturition (GD 6-19) to evaluate its potential for maternal and prenatal developmental toxicity. Analyses confirmed the correctness of the prepared concentrations and the stability of the test substance in the vehicle. The test substance caused neither mortality nor clinical symptoms of systemic toxicity in any of the exposed groups. Two females of the high-dose group (600 mg/kg bw/d) showed transient (up to 10 minutes) salivation at two occasions during the treatment period (GD 14 and GD 17). Such transient salivation shortly after dosing most likely reflects a reaction of the animals to the taste and smell of the test substance. It is not considered to be a sign of systemic toxicity. The high-dose of the test substance (600 mg/kg bw/d) caused a decrease in body weight gain as well as a significant decrease in the corrected (net) body weight gain. These effects are considered minimal, but treatment-related and adverse. No toxicologically relevant clinical effect was noted for the animals exposed to 60, 200 or 300 mg/kg bw/d of the test substance. No differences of toxicological relevance between the control and the treated groups (60, 200, 300 or 600 mg/kg bw/d) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test compound on fetal weight and sex distribution of the fetuses was noted at any dose. Overall, there was no evidence for toxicologically relevant adverse effects of the test substance on fetal morphology at any dose. Thus, the test item is not teratogenic in rats.

Justification for classification or non-classification

The available developmental toxicity study for the structural analogue of the test item is reliable and suitable for classification purposes under Regulation 1272/2008. The source substance is not considered to be classified for fertility or developmental toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480. This non-classifcation is also assumed for the test substance.