[(3aS*,4R*,5S*,7R*,7aS*)-4,7-methano-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-5-yl]methyl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 September 1991 - 31 October 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Fully adequate for assessment. Conducted according to OECD TG 401 Acute Oral Toxicity, which was removed from the OECD Test Guidelines Programme in 2001, the GLP compliant study is considered reliable according to OECD 420, EU B.1bis (Commission directive 2004/73/EC).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

[(3aS*,4R*,5S*,7R*,7aS*)-4,7-methano-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-5-yl]methyl acetate

Molecular formula:

C13H20O2

IUPAC Name:

[(3aS*,4R*,5S*,7R*,7aS*)-4,7-methano-2,3,3a,4,5,6,7,7a-octahydro-1H-inden-5-yl]methyl acetate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma Charles River Wiga, Sandhofer Weg 7, 8741 Sulzfeld
- Weight at study initiation: males 240-260g; females 175-216g
- Fasting period before study: animals were fasted for 16 hours before the study, until 3-4 hours after administration of the test article
- Diet: ab libitum Ssniff-R Alleindiat pellets
- Water: ab libitum
- Housing: Macrolon type III collective cage housing (maximum of 5 per cage)
- Acclimation period: 5-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±3 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light):12 hours dark: 12 hours light
- Illumination: 120 lux artificial lighting 7.00am to 7.00pm

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other:

Details on oral exposure:

VEHICLE: undiluted in a volume of 1.89 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

A preliminary range finding test with a dose of 2000 mg/kg bw was conducted in two female rats. No pre-terminal deaths were observed in the 14-day study period.

Dose was fixed at 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females in the main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately before treatment (day 0) and on days 7 and 14 (termination)
- Necropsy of survivors performed: animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were performed.
- Other examinations performed: clinical observations (Irwin-Screening Procedure) were examined at time intervals of: 10 minutes; 1 hour; 2 hour; 3.5 hour; 6 hour; 24 hour; and thereafter once daily upt to day 14.

Results and discussion

Preliminary study:

A preliminary range finding test with a dose of 2000 mg/kg bw was conducted in two female rats. No pre-terminal deaths were observed.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the course of the study

Clinical signs:

Severe clinical signs, such as reduced activity, abnormal gait, abdominal, lateral or squatting position, piloerection, reduced tone and skin turgor, reduced ear reflex, reduced respiratory rate and reduced audition, were observed up to 6 hours post administration. Signs were mainly in males.

Body weight:

Weight gains were normal in all animals

Gross pathology:

Gross pathological examination at terminal necrospy (day 14) revealed no test article-dependent findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No pre-terminal deaths were observed in the OECD 401 Acute Toxicity study. Thus, the oral LD50 value is >2000 mg/kg bw. There is no evidence of a relevant intrinsic acute oral toxicity requiring classification or substance specific risk mitigation measures (RMM).

Executive summary:

The acute oral toxicity of TCD-M-acetate was investigated in male and female Wistar rats (n=10). On the basis of preliminary testing results, animals were give a single oral administration of 2000 mg/kg bw TCD-M-acetate. Clinical signs, such as reduced activity, abnormal gait, abdominal, lateral or squatting position, piloerection, reduced tone and skin turgor, reduced ear reflex, reduced respiratory rate and reduced audition were observed up to 6-hours post-administration. No pre-terminal deaths were observed in the study, consequently, an LD₅₀could not be established. In accordance with the requirements of the limit test, the LD₅₀value is considered to be >2000 mg/kg bw.