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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

No test item-related adverse general effects and adverse reproduction effects were observed up to 300 mg/kg bw/day (NOAEL).

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Based on expert toxicological judgment (see attached document under in section 13 of this technical dossier), an analogue approach for read-across of the endpoint “Screening for reproductive/ developmental toxicity, one species” from the structural analogue to the target substance is considered justified.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Version / remarks:
2016-07-29
Deviations:
no
Key result
Dose descriptor:
NOAEL
Effect level:
> 300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: absence of adverse toxic effects
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: absence of adverse toxic effects
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
NOAEL (general toxicity; rat): 300 mg/kg bw/day (actual ingested)
NOAEL (reproduction/developmental toxicity; rat): 300 mg/kg bw/day (actual ingested)

After the oral administration of 30, 100, and 300 mg/kg bw/day of the test item to male and female adult rats, no adverse test item-related effects were observed for clinical signs, mortality, body weight, body weight gain, food consumption, gross pathology, and histopathology. In addition, no test item-related changes were observed for reproductive function and reproductive performance. No test item related changes were observed in the thyroid hormone concentration of adult males. Lastly, no adverse test item-related findings were made in the F1 pup generation, when investigating clinical signs, mortality, body weight, sexual maturation, thyroid hormone concentration, and gross pathology.
Under the experimental conditions of this screening study, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity and reproduction/developmental toxicitywas considered to be 300 mg/kg bw/day (unbound).

Based on expert toxicological judgment (see attached document in section 13 of this technical dossier), an analogue approach for read-across of the endpoint “Screening for reproductive/ developmental toxicity, one species” from the structural analogue (test item) to the target substance is considered justified.
Executive summary:

A toxicity to reproduction study was performed with the test item according to the OECD guideline 421 (2016). The test material was suspended in the vehicle (corn oil) and administered by gavage to three groups, each of twelve male and twelve female Crl: CD(SD) rats, at the dose levels of 30, 100, and 300 mg/kg bw/day. The test item was administered once daily to males and females during two weeks prior to mating and continued through the day before sacrifice in males (at least 50 days), and continued through the lactation day 13 in females. A concurrent control group received the vehicle only. General systemic observations including mortality, general clinical signs, body weights, body weight gain, food consumption, macroscopic findings, organ weights (testis, epididymis, prostate and seminal vesicles only) and microscopic findings (testes, epididymis, and ovaries only) were measured and conducted. In addition, reproductive/developmental observations including oestrus cycle, precoital time, fertility data, reproductive and littering findings, F1 pups clinical signs, body weight, anogenital distance, nipple retention and external examination were conducted. Thyroid hormone level in blood was also analysed for adult males and pups at sacrifice.

After the oral administration of 30, 100, and 300 mg/kg bw/day of the test item to male and female adult rats, no adverse test item-related effects were observed for clinical signs, mortality, body weight, body weight gain, food consumption, gross pathology, and histopathology. In addition, no test item-related changes were determined for reproductive function and reproductive performance. No test item related changes were observed in the thyroid hormone concentration of adult males. Lastly, no adverse test item-related findings were made in the F1 pup generation, when investigating clinical signs, mortality, body weight, sexual maturation, thyroid hormone concentration, and gross pathology.

Under the experimental conditions of this screening study, the No Observed Adverse Effect Levels (NOAELs) for systemic toxicity and reproduction/developmental toxicity were considered to be 300 mg/kg bw/day (unbound).

Read-across approach is considered to be feasible since the structural analogue (test item) and the target substance have negligibly minor differences in structure, properties and transformation pathways.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In reproductive observations, no test item-related change was observed in estrus cycle, precoital time, fertility data, reproductive and littering findings.n reproductive observations, no test item-related change was observed in estrus cycle, precoital time, fertility data, reproductive and littering findings.

Effects on developmental toxicity

Description of key information

No test item-related adverse developmental effects were observed up to 300 mg/kg bw/day (NOAEL).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
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

In developmental observations, no test item-related change was observed in reproductive and littering findings, F1 pups clinical signs, body weight, anogenital distance, nipple retention and external examination.

Justification for classification or non-classification

In a reproductive toxicity screening test (OECD 421) no adverse test item-related effects were observed for clinical signs, mortality, body weight, body weight gain, food consumption, gross pathology, and histopathology. In addition, no test item-related changes were determined for reproductive function and reproductive performance. No test item related changes were observed in the thyroid hormone concentration of adult males. Lastly, no adverse test item-related findings were made in the F1 pup generation, when investigating clinical signs, mortality, body weight, sexual maturation, thyroid hormone concentration, and gross pathology. Under the experimental conditions of this screening study, the No Observed Adverse Effect Levels (NOAELs) for systemic toxicity and reproduction/developmental toxicity were considered to be 300 mg/kg bw/day.

The criteria for classification for the endpoint reproductive toxicity in accordance with regulation 1272/2008 are not met, since no adverse effects on sexual function and fertility and on development were seen.

Based on expert toxicological judgment (see attached document in section 13 of this technical dossier), an analogue approach for read-across of the endpoint “Screening for reproductive/ developmental toxicity, one species” from the structural analogue (test item)  to the target substance is considered justified.

Additional information