Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

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

The test substance was not examined for toxicity to reproduction and development. Reliable experimental data of an analogue substance are available. In a prenatal developmental toxicity study the 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 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 CGL 400. 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 preand 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.

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 document for the read-across justification
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Species:
rat
Key result
Dose descriptor:
NOEL
Effect level:
195 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Remarks on result:
other: Read-across from EC 410-560-1, effect value corrected for the difference in molecular weight
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOEL
Effect level:
>= 390 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Absence of developmental toxic effects at highest dose level
Remarks on result:
other: Read-across from EC 410-560-1, corrected for the difference in molecular weight
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
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

Read across justification

The test substance was not examined for toxicity to reproduction and development. Reliable experimental data of an analogue substance are available. Both materials share high similarity in molecular structure and physico-chemical parameters. Furthermore, the analogue substance has a lower molecular weight which gives an additional safety margin.

The test item was tested for its prenatal developmental toxicity in Wistar rats. The test substance was administered as an oily solution to groups of 25 time-mated female Wistar rats by gavage at doses of 60, 200, 300 and 600 mg/kg body weight/day (mg/kg bw/d) on gestation days (GD) 6 through 19. Two control groups, consisting of 25 females, each, were dosed with the vehicle (corn oil) in parallel. A standard dose volume of 4 mL/kg body weight was used for each test group.

As scheduled in the study plan, the high-dose level for this study was 600 mg/kg body weight/day which was intended to be administered to test group 3. Because of a mistake, an incorrect dose level was applied to test group 3; the actually administered dose was 300 mg/kg bw/d throughout the entire study. Therefore, an additional dose group of 600 mg/kg bw/d (test group 5) and a control group (test group 4) were added to the study to cover the dose range as originally specified in the study plan.

The following test substance-related, adverse effects/findings were noted: Decreased mean body weight gain of the dams in the high dose group during treatment period (GD 6-19), (about 10% below concurrent control) and decreased corrected body weight gain (about 18% below concurrent control). In fetuses of this test group no adverse findings were observed. No test substance-related adverse effects were observed in dams or fetuses of other dose level groups.

Under the conditions of this prenatal developmental toxicity study, the oral administration to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) at a dose of 600 mg/kg bw/d 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.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008 (CLP)


The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for reproductive  toxicity under Regulation (EC) No. 1272/2008.

Additional information

Categories Display