Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 02 to December 14, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to standard guideline.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study was performed according to procedure suggested by Hagan (1959) and is similar to the OECD Test Guideline No. 401.

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Molecular formula:

C12H18O

IUPAC Name:

Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): 5. 0878/2
- Other: Specific gravity: 1.05

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA.
- Weight at study initiation: 150-300 g
- Fasting period before study: Animals were fasted overnight prior to administration of test material.
- Diet: Wayne animal feed, ad libitum
- Water: Water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS: Animals were maintained under standard laboratory conditions.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.26 mL/kg bw

Doses:

Range-finding study: 500, 1000 and 2000 mg/kg bw
Main study: 100, 500, 600, 750 and 1260 mg/kg bw

No. of animals per sex per dose:

1 male/dose (range-finding study)
3/sex/dose (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed for signs of pharmacologic activity and toxicity at 1, 3, 6 and 24 h after test material administration and then daily for 14 days. Initial and final body weight of each animal was recorded.
- Necropsy of survivors performed: Yes; animals were sacrificed at the end of the 14-day observation period and were subjected to gross necropsy.

Statistics:

Litchfield and Wilcoxon (1949)

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

410 mg/kg bw

Based on:

test mat.

95% CL:

273 - 615

Mortality:

- In the range finding study, a male animal treated with 100 mg/kg bw dose was died at 1 h after dosing and another male animal treated with 200 mg/kg bw dose was died at 30 minutes after dosing. 0, 100 and 100 % mortality were observed at 500, 1000 and 2000 mg/kg bw, respectively
- In the main study, mortality was observed at all dose levels: 1/6 (1 female), 2/6 (2 females), 5/6 (3 males + 2 females), 6/6 (3 males + 3 females) and 6/6 (3 males + 3 females) at 100, 500, 600, 750 and 1260 mg/kg bw, respectively. 17, 33, 83, 100 and 100 % mortality were observed at 100, 500, 600, 750 and 1260 mg/kg bw, respectively.

Clinical signs:

other: - Range-finding study: Slight depression was observed in a male animal treated with 500 mg/kg bw after 1 h of dosing and appeared normal thereafter. - Main study: Slight depression and convulsions were observed in 5/6 animas treated with 1260 mg/kg bw wit

Gross pathology:

- No abnormality was observed at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 Combined = 410 mg/kg bw (95 % confidence limits of 273-615 mg/kg bw)

Executive summary:

In an acute oral toxicity study, groups of Wistar rats (3/sex/dose) were administered a single oral (gavage) dose of test material at 100, 500, 600, 750 and 1260 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Range finding study was conducted at the dose levels of 500, 1000 and 2000 mg/kg bw (1 male/dose) to determine the dose for main study.

In the range finding study, 0, 100 and 100 % mortality were observed at 500, 1000 and 2000 mg/kg bw, respectively. Slight depression was observed in a male animal treated with 500 mL/kg bw.

In the main study, 17, 33, 83, 100 and 100 % mortality were observed at 100, 500, 600, 750 and 1260 mg/kg bw, respectively. Slight depression and convulsions were observed in all animals at 1260 mg/kg bw. Surviving animals showed slight increase in body weight gain over the 14 day observation period. No abnormality was observed at necropsy.

Oral LD50 Combined = 410 mg/kg bw (95 % confidence limits of 273-615 mg/kg bw)

 

Under the test conditions, the test material is classified as ‘Category 4: Harmful if swallowed’ according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.