Indeno[4,3a-b]furan, decahydro-2,2,7,7,8,9,9-heptamethyl-

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

In vivo screening for screening for reproductive / developmental toxicity: rat, (OECD TG 421, GLP).

- Systemic NOAEL: > 64 and 83 mg/kg bw/day for males and females, respectively

- Fertility NOAEL: >64 and 81 mg/kg bw/day for males and females, respectively,

- Development NOAEL: 81 mg/kg bw/day

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

64 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

An oral reproscreening study (OECD TG 421, GLP) is available. This study adequately covers this endpoint.

Additional information

Screening for Reproduction/ Developmental Toxicity - OECD TG 421 - Fertility and Developmental toxicity

In a reproduction/developmental toxicity screening test that was performed according to OECD TG 421 and under GLP conditions, 12 Wistar rats/sex/dose received diets containing the test substance at concentrations of 0, 15, 50 and 150 mg/kg bw (0, 225, 750 or 1500 mg/kg diet) during a premating period of 2 weeks and during mating (1 week), gestation and lactation until postnatal day 4. The test substance was homogeneously distributed in the diets and stable in diet stored in an open container for 24 hours, except for the high-dose level (-11 %). When stored in a closed container in the freezer (< -18°C), the high dose of the test substance in diet was stable for 5 weeks. The concentration of the test substance was lower than intended in all diets. Relative differences of -28 %, -26 % and -14 % were observed for the measured concentrations in the low-, the mid- and the high dose group, respectively.

Results: Daily clinical observations did not reveal any treatment-related changes in the animal's appearance, general condition or behaviour. No treatment-related effects were observed in mean body weight, body weight changes and food consumption throughout the study. Relative liver weight was statistically significant increased with 10.6 and 12.7% in mid dose and high dose males, respectively, but not in females. The toxicological relevance of this finding is doubtful, because there was no clear dose-response and no histopathological changes in the liver were observed. Macroscopic and microscopic examination of organs did not reveal any treatment-related changes. No treatment-related effects were observed on pre-coital time, mating index, female fecundity index, male and female fertility indices, gestation index, duration of gestation, number of corpora lutea, implantation sites, lost implantations and the calculated indices, pre- and post implantation loss. No effects were observed on litter size, pup sex and weight and pup survival. Macroscopic observations of stillborn pups or pups that died during lactation did not reveal any treatment-related changes.

Conclusion: The results of the reproduction/developmental toxicity screening test in rats indicate no systemic, fertility, and developmental toxicity up to and including the highest dose tested 100 mg/kg bw (1500 mg/kg diet, nominal concentration). In male rats, the NOAEL for systemic toxicity and fertility was established to be at least 64 mg/kg bw/day based on the actual dose of test substance ingested. In female rats, the NOAEL for systemic toxicity was established to be at least 83 mg/kg bw/day and the NOAEL for fertility and development was at least 81 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

For the test substance a Reproduction/ developmental toxicity screening test (OECD TG 421 in compliance with GLP) is available in which no maternal systemic and developmental effects were observed resulting in NOAELs for systemic and developmental toxicity of >=80 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

81 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

A GLP compliant oral reproscreening study (OECD 421) is available and this study adequately covers this endpoint for this tonnage level

Justification for classification or non-classification

The substance does not have to be classified for toxicity to reproduction toxicity (both fertility and development) according to EU CLP (EC No. 1272/2008 and its amendments)