(3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Data on a single study reported in different reports or publications.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Method not detailed. Six male and six female Fischer 344 rats, and female C57BL/6 mice were exposed to varying concentrations of test material vapor for calculating LC50.

GLP compliance:

no

Remarks:

Prior to GLP but conducted according to the "Guide for the Care and Use of Laboratory Animals," Institute of Laboratory Animal Resources, National Research Council.

Test type:

acute toxic class method

Limit test:

no

Species:

other: rats and mice (and hamsters)

Strain:

other: Fischer 344 rats ; C57BL/6 mice ; Goden Syrian hamsters

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass chamber
- Exposure chamber volume: 9 L

Duration of exposure:

ca. 4 h

Remarks on duration:

6h for hamsters

Concentrations:

Rats and hamsters : Not reported ("varying concentrations")
Mice: varying concentrations including 1000 ppm

No. of animals per sex per dose:

6 rats/sex. 6 female mice. Not specidied for hamsters.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 1 221 ppm

Based on:

test mat.

95% CL:

ca. 1 174 - ca. 1 259

Exp. duration:

4 h

Remarks on result:

other: rats

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 1 194 ppm

Based on:

test mat.

95% CL:

ca. 1 107 - ca. 1 287

Exp. duration:

4 h

Remarks on result:

other: rats

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 930 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mice

Remarks:

An exact LC50 was not obtained as the difference between zero and 100% mortality was so slight that an attempt to achieve partial mortality was not made. A concentration of 900 ppm resulted in no deaths while 955 ppm caused complete mortality.

Mortality:

Yes but no details.

Clinical signs:

other: Eye irritation, fine tremors, prostration, ataxia. Death during exposure was preceded by clonic convulsions. Survivors of high concentrations exhibited hind quarter paralysis.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the test conditions, the estimated inhalation LC50 after a 4-hour exposure period were 1221 and 1194 ppm for male and female rats, respectively and 930 ppm for female mice. Therefore, the test substance is classified in Category 3 for acute toxicity by inhalation.

Executive summary:

In an acute inhalation toxicity study performed in 1979, six male and six female Fischer 344 rats, and female C57BL/6 mice were exposed to varying concentrations of test material during 4 hours. Male Golden Syrian hamsters were exposed to saturated vapor pressure concentrations during 6 hours.

Gross signs of toxicity during exposure included tremors and ataxia.

Death during exposure was preceded by fine tremors, prostration and clonic convulsions. Survivors of high concentrations exhibited hind quarter paralysis which lasted throughout the 14 -day observation period or to time of death, whichever occured first.

No mortality was observed in hamsters.

All of 6 mice exposed to 1000 ppm died within 4 hours.

LC50 (M rats) = 1221 (1174 -1259) ppm, ca. 6803 (6542 - 7015) mg/m3, ca. 6.803 (6.542 - 7.015) mg/L.

LC50 (F rats) = 1194 (1107 -1287) ppm, ca. 6653 (6168 - 7171) mg/m3, ca. 6.653 (6.168 - 7.171) mg/L.

LC50 (F mice) = 930 ppm (Confidence limits could not be calculated), ca. 5182 mg/m3, 5.182 mg/L.

Under the test conditions, the substance is classified in Category 3 for acute toxicity by inhalation according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 3

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Guideline:

other:

Principles of method if other than guideline:

Method not detailed. Five male and five female Fischer 344 rats, five female CS7BL/6 mice and five male Golden syrian hamsters were treated with undiluted test substance at a maximum dose level of 20 mL/kg body weight and observed for 14 days.

GLP compliance:

no

Remarks:

Pre-GLP but the experiments were conducted according to the "Guide for the Care and Use of Laboratory Animals," Institute of Laboratory Animal Resources, National Research Council.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene

EC Number:

220-585-8

EC Name:

(3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene

Cas Number:

2825-82-3

Molecular formula:

C10H16

IUPAC Name:

(1R,2S,6R,7S)-tricyclo[5.2.1.0^{2,6}]decane

Test material form:

liquid

Test animals

Species:

other: rats, mice and hamsters

Strain:

other: rats: Fischer 344; mice: C57BL/6; hamsters: Golden Syrian

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Doses:

20 mL/kg bw

No. of animals per sex per dose:

rats: 5/sex/dose; mice: 5 females/dose; hamsters: 5 males/dose

Control animals:

no

Details on study design:

Five male and five female Fischer 344 rats, five female CS7BL/6 mice, five male Golden syrian hamsters; maximum dose of 20 mL/kg body weight; observation for 14 days.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Rats

Remarks:

ca. LD50 > 18.8 g/kg bw

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 20 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Hamsters

Remarks:

ca. LD50 > 18.8 g/kg bw

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 3.9 mL/kg bw

Based on:

test mat.

95% CL:

>= 2.2 - <= 6.9

Remarks on result:

other: Mice

Remarks:

LD50 calculated using the moving average method of Weil. ca. LD50 = 2.8 g/kg bw

Mortality:

Partial mortality in rats and hamsters.
In mice, all deaths occurred within 48 hours of dosing.

Clinical signs:

other: Convulsions were observed immediately preceding death.

Gross pathology:

Necropsy of dead revealed congested lungs and GI tract.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions, the substance is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in Category 5 according to the GHS as the worst-case estimated oral LD50 is between 2000 and 5000 mg/kg bw.

Executive summary:

In an acute oral toxicity study performed in 1979, five male and five female Fischer 344 rats, five female C57BL/6 mice and five male Golden syrian hamsters were treated with undiluted test material at a dose level of 20 mL/kg bw. Animals were then observed for 14 days.

Deaths observed in rats and hamsters but not enough to determine a LD50 value. In mice, deaths occurred within 48 hours of dosing with convulsions were observed immediately preceding death.

Necropsy of dead revealed congested lungs and GI tract.

In rats and hamsters, oral LD50 > 20 mL/kg bw, which is equivalent to 18.8 g/kg bw.

In female mice, oral LD50 = 3.9 mL/kg bw, which is equivalent to 2.8 g/kg bw.

Under the test conditions, the substance is not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in Category 5 according to the GHS as the worst-case estimated oral LD50 is between 2000 and 5000 mg/kg bw.

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