Reaction mass of 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate and 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-04-02 to 1979-04-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted similarly to OECD Guideline 401 with deviations: no data about purity and no certificate of analysis of the test substance; no. of animals at two dose levels < 5; no details on environmental conditions; observation period: 7 days

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

non-GLP study; no data about purity and no certificate of analysis of the test substance; no. of animals at two dose levels < 5; no details on environmental conditions; observation period: 7 days

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

EC Number:

268-259-4

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Cas Number:

68039-44-1

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-6-yl pivalate

Constituent 2

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

EC Number:

268-261-5

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

Cas Number:

68039-45-2

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-5-yl pivalate

impurity 1

Reference substance name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Molecular formula:

C15H22)2

IUPAC Name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Test material form:

other: liquid, may crystalize to white solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): PM 343 Pivaloxycyclene
- Source: Proprietary Perfumes Ltd., UK
- Date received: 29 March 1979
- Physical state: Very pale yellow oily liquid
- Specific gravity: 1.01
- pH: 6.0

Test animals

Species:

mouse

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-5 weeks
- Housing: Animals were housed in individual cages.
- Fasting period before study: 4 h
- Diet: Commercial pelleted diet, ad libitum
- Water: Ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME ADMINISTERED: 10 mL/kg bw

Doses:

2, 5 and 10 mL/kg bw

No. of animals per sex per dose:

5 mL/kg bw: 3/sex/dose
2 and 10 mL/kg bw: 1/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Survivors were weighed before killing for post-mortem examination at the end of the one week observation period.
- Necropsy of survivors or dead animals performed: Yes

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 5330 mg/kg bw; calculated using the density of 1.066 g/L (literature)

Mortality:

- Both mice (2/2) dosed at 10.0 mL/kg bw and 4/6 mice dosed at 5.0 mL/kg bw died within 24-48 h after treatment.
- Mortalities at 2, 5 and 10 mL/kg were 0, 67 and 100 %, respectively.

Clinical signs:

- None of the animals were showing symptoms at 2 h after treatment.
- After 18 h, both mice dosed at 10.0 mL/kg bw and 4/6 mice dosed at 5.0 mL/kg bw were comatose, hypothermic, showing signs of stress and exhibiting laboured breathing. Two other mice dosed at 5.0 mL/kg bw appeared unaffected.
- Female mouse dosed at 2 mL/kg bw was showing signs of stress at 18 h after treatment, but recovered within 42 h.

Body weight:

- Surviving animals gained weight during the 7 day observation period.

Gross pathology:

- Autopsy of the animals that died revealed gaseous distension of the stomach and irritation and gaseous distension of the duodenum and ileum with blood stained contents present.
- Where the stomach was in contact with the liver this organ appeared bleached and the mice also had pale kidneys.
- Other findings included congestion of the lungs, prominent distended gall bladders and distension of the bladder due to the presence of pale yellow urine.
- Surviving animals presented a normal appearance at autopsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of PM 343 Pivaloxycyclene is higher than 2000 mg/kg bw in mice therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.

Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, groups of mice were given a single oral dose of the test item, PM 343 Pivaloxycyclene, at 2, 5 and 10 mL/kg bw. Numbers of animals in the respective group were 1, 3 and 1 mice/sex/dose. Animals were observed for mortality, clinical signs and bodyweights for 7 days and were all macroscopically necropsied after sacrifice.

Mortalities at 2, 5 and 10 mL/kg were 0, 67 and 100 %, respectively. Surviving animals gained weight during the 7 day observation period and presented a normal appearance at autopsy. None of the animals were showing symptoms at 2 h after treatment. After 18 h, both mice dosed at 10.0 mL/kg bw and 4/6 mice dosed at 5.0 mL/kg bw were comatose, hypothermic, showing signs of stress and exhibiting laboured breathing. Two other mice dosed at 5.0 mL/kg bw appeared unaffected. Female mouse dosed at 2 mL/kg bw was showing signs of stress at 18 h after treatment, but recovered within 42 h. Autopsy of the animals that died revealed gaseous distension of the stomach and irritation and gaseous distension of the duodenum and ileum with blood stained contents present. Where the stomach was in contact with the liver this organ appeared bleached and the mice also had pale kidneys. Other findings included congestion of the lungs, prominent distended gall bladders and distension of the bladder due to the presence of pale yellow urine. In this study, the combined oral LD50 of the test item, PM 343 Pivaloxycyclene, in mice was considered to be approximately 5 mL/kg bw [equivalent to 5330 mg/kg bw; calculated using the density of 1.066 g/L (literature)].

The oral LD50 of PM 343 Pivaloxycyclene is higher than 2000 mg/kg bw in mice therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.