A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproduction screening test (OECD TG 421): The parental NOAEL was determined to be >=550 mg/kg bw based on the absence of toxic adverse effects in the parental animals. The fertility NOAEL is >= 550 mg/kg bw based on the absence of reproductive toxicity.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

550 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The information from the reproscreen study and from the information on the gonads of males and females in the 28-day repeated dose study have been derived from OECD/EC guidelines under GLP and are of high quality.

Additional information

In a Reproscreen study (OECD TG 421, GLP), the test substance was administered via the diet to Sprague-Dawley rats at dosages of 70, 170 or 550 mg/kg bw. Control animals received a plain diet. All parameters from the OECD TG 421 have been recorded. The following results were found:

Clinical signs: No effects were seen on body weight (gain) and food consumption. Some piloerection was seen in the females. (Relative) liver weights were increased in males and females in the high dose and minimal liver hepatocellular hypertrophy was noted at minimal degree and was considered to be an adaptive non adverse finding. Adrenal weights were decreased but no macroscopic or microscopic findings related to treatment were noted.

Fertility: Mating index, fertility index, conception index, gestation index and duration of gestation index were not affected by the substance.

Based on the absence of toxicologically relevant effects, the parental NOEAL and the NOAEL for reproduction were determined to be >= 550 mg/kg bw.

Effects on developmental toxicity

Description of key information

Reproductive screening test (OECD TG 421): The parental NOAEL was determined to be >=550 mg/kg bw based on the absence of toxic adverse effects in the parental animals. The developmental NOAEL is >= 550 mg/kg bw based on the absence of developmental toxicity in the first generation animals.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

550 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The information from the reproscreen study has been derived from OECD/EC guidelines under GLP and is of high quality.

Additional information

In a Reproscreen study (OECD TG 421, GLP), the test substance was administered via the diet to Sprague-Dawley rats at dosages of 70, 170 or 550 mg/kg bw. Control animals received a plain diet. All parameters from the OECD TG 421 have been recorded. The following results were found:

Clinical signs: No effects were seen on body weight (gain) and food consumption. Some piloerection was seen in the females. (Relative) liver weights were increased in males and females in the high dose and minimal liver hepatocellular hypertrophy was noted at minimal degree and was considered to be an adaptive non adverse finding. Adrenal weights were decreased but no macroscopic or microscopic findings related to treatment were noted.

Developmental: Number of dead and living pups at first litter check, postnatal loss, viability index and sex ratio were unaffected by treatment. Two pups of the control group, two pups at 1.000 ppm and one pup at 2.500 ppm were found dead or missing during the first days of lactation. No toxicological relevance was attributed to these dead/missing pups since the mortality incidence did not show a dose-related trend and remained within the range considered normal for pups of this age.

Based on the absence of toxicologically relevant effects, the parental NOEAL and the NOAEL for development were determined to be >= 550 mg/kg bw.

Justification for classification or non-classification

Based on the results of the available Repeated dose and Reproductive toxicity studies, the substance does not have to be classified for reproductive toxicity (fertility and developmental toxicity) according to EU CLP (EC 1272/2008 and its amendments).