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Description of key information

Repeated dose toxicity: Oral

Short term repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS). The study was performed using rats at dose levels of 0, 20, 100 or 500 mg/Kg bw by the oral gavage route for 28 days. The animals were observed for clinical signs, mortality, changes in body weight, organ weight and histological examination was performed at necropsy.No clinical signs were observed during the test.No mortality were observed during the test.No treatment-related body weight changes were seen in all animals.There was a temporary decrease in the consumption of food in the test group, in females from group 4.

The clinical biochemistry findings related to the test substance consist of:

- decreased glucose levels in males at 100 mg / kg / day and in both sexes at 500 mg / kg / day,

- increase in total cholesterol, triglycerides and phospholipids in females at 500 mg / kg / day

- stronger activity of gamma-glutamyltransferase in both sexes at 500 mg / kg / day,

- increased calcium levels in males and at females of groups 4

- decrease in potassium levels in both sexes at the dose 500 mg / kg / day.

At 500 mg / kg / day, there was an increase in the weight of liver in both sexes, at 100 mg / kg / day this effect is no longer observed that in males.

In males of group 4 we also observe a increased kidney weight and decreased weight thymus. There were also lower thymus weights in males at 100 mg / kg / day.

Liver (bigger) size increased in a male at 500 mg / kg / day.There were microscopic changes on male kidneys at 100 mg / kg / day and 500 mg / kg / day. These changes consisted of tubular basophilia and tubular mineralization at the corticomedullary junction accompanied by tubular hyaline calculus in a single male treated at 500 mg / kg / day.The No Observed Adverse Effect Level (NOAEL) and No Observable Effect Level (NOEL) for (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS) is considered to be 20 mg/kg bw/day when rats were repeatedly exposed to the test chemical for 28 days.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
20 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Repeated dose toxicity: Oral

Data available for the target chemical was reviewed to determine the toxic nature of (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS)(CAS no198404-98-7). The study is as mentioned below:

Short term repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS). The study was performed using rats at dose levels of 0, 20, 100 or 500 mg/Kg bw by the oral gavage route for 28 days. The animals were observed for clinical signs, mortality, changes in body weight, organ weight and histological examination was performed at necropsy.No clinical signs were observed during the test.No mortality were observed during the test.No treatment-related body weight changes were seen in all animals.There was a temporary decrease in the consumption of food in the test group, in females from group 4.

The clinical biochemistry findings related to the test substance consist of:

- decreased glucose levels in males at 100 mg / kg / day and in both sexes at 500 mg / kg / day,

- increase in total cholesterol, triglycerides and phospholipids in females at 500 mg / kg / day

- stronger activity of gamma-glutamyltransferase in both sexes at 500 mg / kg / day,

- increased calcium levels in males and at females of groups 4

- decrease in potassium levels in both sexes at the dose 500 mg / kg / day.

At 500 mg / kg / day, there was an increase in the weight of liver in both sexes, at 100 mg / kg / day this effect is no longer observed that in males.In males of group 4 we also observe a increased kidney weight and decreased weight thymus. There were also lower thymus weights in males at 100 mg / kg / day.Liver (bigger) size increased in a male at 500 mg / kg / day.There were microscopic changes on male kidneys at 100 mg / kg / day and 500 mg / kg / day. These changes consisted of tubular basophilia and tubular mineralization at the corticomedullary junction accompanied by tubular hyaline calculus in a single male treated at 500 mg / kg / day.The No Observed Adverse Effect Level (NOAEL) and No Observable Effect Level (NOEL) for (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS) is considered to be 20 mg/kg bw/day when rats were repeatedly exposed to the test chemical for 28 days.

Additional information

Justification for classification or non-classification

Based on the data available for the target chemical (1-METHYL-2-(1,2,2-TRIMETHYLBICYCLO(3.1.0)-HEX-3-YLMETHYL)CYCLOPROPYL)METHANOL( MIXTURE OF DIASTEREOISOMERS)(CAS no 198404-98-7) is not likely to be a toxic upon repeated exposure by oral route.