2-ethoxy-1,3-dimethylcyclohexane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the absence of adverse effects on male and female fertility and reproductive performance, the NOAEL was determined to be 500 mg/kg in an combined 28 day repeated dose toxicity study with reproductive/developmental screening assay according to OECD TG 422.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

IFF 05-0293 was administered by daily oral gavage to male and female Wistar Han rats at dose levels

of 50, 150 and 500 mg/kg. Males were exposed for 2 weeks prior to mating, during mating, and up to

termination (for 29 days). The females were exposed for 2 weeks prior to mating, during mating,

during post-coitum, and at least 4 days of lactation (for 40-53 days).

Formulation analysis showed that the formulations were prepared accurately and homogenously.

Reproductive results:

No reproduction toxicity was observed up to the highest dose level tested (500 mg/kg).

No treatment-related changes were noted in any of the reproductive parameters investigated in this

study (i.e. mating, fertility and conception indices, precoital time, and numbers of corpora lutea and

implantation sites, spermatogenic profiling, and histopathological examination of reproductive organs).

Three control females did not deliver offspring; two were not pregnant and one control female showed

no evidence of mating, No abnormalities were seen in the reproductive organs, which could account

for their lack of offspring. It was considered that sufficient control data were available to allow for a

valid interpretation of the study data, also considering the absence of reproductive and developmental

toxicity up to the highest dose tested in this study.

Developmental results:

No developmental toxicity was observed up to the highest dose level tested (500 mg/kg).

No treatment-related changes were noted in any of the developmental parameters investigated in this

study (i.e. gestation index and duration, parturition, maternal care and early postnatal pup

development consisting of mortality, clinical signs, body weight and macroscopy).

In conclusion, treatment with IFF 05-0293 by oral gavage in male and female Wistar Han rats at dose

levels of 50, 150 and 500 mg/kg revealed adverse parental effects in males only, consisting of

degenerative lesions in the kidneys at 50 mg/kg and higher. No reproduction and developmental

toxicity was observed for treatment up to 500 mg/kg.

Based on these results, the following No Observed Adverse Effect Levels (NOAEL) were derived:

Parental NOAEL (males): - below 50 mg/kg (based on degenerative kidney lesions (i.e. granular

casts and tubular basophilia, related to hyaline droplet accumulation)

- At least 500 mg/kg, when male rat specific kidney findings are

disregarded.

Parental NOAEL (females): at least 500 mg/kg

Reproduction NOAEL: at least 500 mg/kg

Developmental NOAEL: at least 500 mg/kg

Justification for classification or non-classification

Based on the results of the combined oral repeated dose toxicity study and reproduction/developmental toxicity screening test, the test substance does not have to be classified for reproduction toxicity in accordance with Regulation (EC) No. 1272/2008.