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Key value for chemical safety assessment

Effects on fertility

Additional information

There is no study available on fertility testing of ITC288 compiling all endpoints required in an OECD 421/422 study. However, effects of ITC288 on estrous cycle, seminology and histopathology of reproductive organs were monitored in a 90 day study via additional evaluations showing no dose response effects for the tested concentration of 100, 300 and 1000 mg/kg bw/day. The OECD414 study on ITC288 showed no significant effects for the same tested concentration both on maternal parameters and embryo-fetal development. As a conclusion on both endpoints the NOAEL is considered to be 1000 mg/kg bw/ day.

The fertility toxicity (sexual behaviour, survival of pups and post natal development is therefore not directly assessed on ITC288 but a read across approach based on HEDP results, a substance harbouring a comparable physico chemical and a comparable to more severe toxicological profile, is used to demonstrate an absence of significant effects on these two endpoints. Additional information on the Read across strategy is given in chapter 13.

Short description of key information:

No specific studies on reproduction are available. Data on effects on reproductive organs were assessed from the subchronic oral toxicity study (Parr2014) showing no significant effects on seminology, estrous cycle and histopathology of testis and oavaris. A developmental toxicity study (OECD414) was also presenting no effects (Bentz 2014).

Effects on developmental toxicity

Description of key information

The test item, ITC288 (batch No. B288P22E1), was administered by gavage, once daily, from Days 6 to 20 p.c., inclusive, to time-mated female Sprague-Dawley rats at dosages of 100, 300 and 1000 mg/kg/day. No effects were observed for these concentration the NOAEL for ITC288 is considered to be 1000 mg/kg/day.

On the basis of the results obtained in the available OECD 414 study:

The No Observed Adverse Effect Level (NOAEL) for maternal parameters was considered to be 1000 mg/kg/day, based on the absence of adverse effects on the dams at the dose-level.

The NOAEL for embryo-fetal development was considered to be 1000 mg/kg/day, based on the absence of adverse effects on the offspring development at the dose-level.

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:
One study was generated and this study is considered as realiable K1, following GLP and OECD414 protocol
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

One study evaluating the prenatal development endpoint is available. The objective of this study was to evaluate the potential toxic effects of the substance, ITC288, on the pregnant female rat and on embryonic and fetal development, following daily oral administration (gavage) to pregnant female rats from implantation to the day prior to the scheduled hysterectomy (Day 6 to Day 20 post-coitum (p.c.) inclusive) acording to the OECD 414 guideline. The test item concentrations tested were 100, 300 and 1000 mg/kg expressed as active ingredient. At termination on Day 21 p.c., there were 20, 24, 22 and 24 dams with live fetuses at 0, 100, 300 and 1000 mg/kg/day, respectively.There were no premature deaths and no test item treatment-related clinical signs, no test item treatment-related effects on mean food consumption, mean body weight, mean body weight gain, mean gravid uterus weight and mean hysterectomy data.There were no toxicologically relevant effects on mean carcass weight and mean net body weight change. There were no test item treatment-related macroscopic findings at necropsy. There were no effects on sex ratio, mean placenta weight and mean fetal/placenta weights ratio. There were no toxicologically significant effects on mean fetal weight. There were no test item treatment-related variations or malformations at external, soft tissues and skeletal examinations.

The test item, ITC288 (batch No. B288P22E1), was administered by gavage, once daily, from Days 6 to 20 p.c., inclusive, to time-mated female Sprague-Dawley rats at dosages of 100, 300 and 1000 mg/kg/day. Since no effects were observed for these concentration the NOAEL for ITC288 is considered to be 1000 mg/kg/day

Justification for selection of Effect on developmental toxicity: via oral route:

The selected study is considered as realiable K1, following GLP and OECD414 protocol

Justification for classification or non-classification

Fertility:

ITC 288/S is not classified for fertility effects due to absence of identified effects.

Development:

Based on the available OECD 414 data, no effects were identified.

ITC 288/S is considered as not toxic to reproduction, therefore no classification is required according to the EU legislation (Directive 67/548/EEC and CLP regulation (1272/2008).