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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Apr 1981 to May 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Four animals were used instead of five and they were not of the same sex
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl rel-acetate
Molecular formula:
C12H22O2
IUPAC Name:
(1R)-1-[(1S)-3,3-dimethylcyclohexyl]ethyl rel-acetate
Constituent 2
Chemical structure
Reference substance name:
(1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate
Molecular formula:
C12H22O2
IUPAC Name:
(1R,2R)‐2,6,6‐trimethylcycloheptyl rel‐acetate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males 101 – 134 g and females 100 - 117g
- Fasting period before study: overnight before treatment

IN-LIFE DATES: April/May 1981

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered at a range of dosage volumes of 6.88 to 17.2 mL/kg body weight.
Doses:
6.4, 8.0 10.0 and 16.0 g/kg body weight
No. of animals per sex per dose:
2
Control animals:
yes
Remarks:
Rats treated with distilled water (17.2 mL/kg) served as controls.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
- Examinations performed: a record was kept of all mortalities and signs of toxicity. All rats that died were examined macroscopically in an attempt to identify the target organs, and those animals surviving termanally were similarly examed to detect posibible residual damage.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 400 - < 16 000 mg/kg bw
Based on:
test mat.
Mortality:
Death occurred in rats treated at 8.0 g/kg and above from within one hour to 22 hours of dosing.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing amongst treated rates included pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, a decreased respiratory rate, pallor of the extremities, increased salvation, ataxia and ptosis. These findings were accompanied by:
- diarrhoea and râles amongst rats at 6.4 and 10.0 g/kg;
- diuresis in rats at 6.4, 8.0 and 10.0 g/kg;
- gasping respiration in one rat at 8.0 g/kg and all rats at 10.0 g/kg;
- a comatose-like condition prior to death in one rat at 8.0, 10.0 and 16.0 g/kg;
- facial oedema in two rats at 16.0 g/kg
Recovery of the surviving animals, as judged by external appearance and behaviour was apparently complete within eight days of dosing.
Body weight:
Reduced body weight gains were seen in one male and one female at 6.4 g/kg during the first week of observation and in one female at 10.0 g/kg during the second week of observation, compared to the controls. Body weight gains of the remaining animals were normal throughout the two-week observation period.
Gross pathology:
Autopsy of the rats that died within one hour to 22 hours of dosing revealed congestion in the lungs and pallor of the liver, spleen and kidneys. A haemorrhagic appearance of the glandular region of the stomach and a dark colouration of the kidney medulla was observed in one male at 8.0 g/kg.
Thermal autopsy findings were within normal limits.

Any other information on results incl. tables

Table 1: Mortality ratio and individual body weights (g) of rats dosed orally with the test substance

Sex

Dosage
(g/kg)

Body weight (g) at

Mortality ratio: (no. of deaths /no. dosed)

time of death after dosing (hours)

Dosing

Week 1

Week 2

0

134

204

255

0/2

-

119

168

227

6.4

124

148

205

0/2

-

127

182

232

8.0

113

DIED

-

2/2

< 15 minutes -

< 6 hours

102

DIED

-

10.0

124

195

263

1/2

>5 -<22

123

DIED

-

16.0

101

DIED

-

2/2

 >5 -<22

119

DIED

-

0

116

158

182

0/2

-

117

167

190

6.4

113

144

166

0/2

-

110

161

192

8.0

100

148

182

0/2

-

102

154

185

10.0

106

147

156

1/2

>5 -<22

107

DIED

-

16.0

103

DIED

-

2/2

<1-<22

Table 2: Signs of reaction to treatment ratio of rats dosed orally with the test substance

Sign

Signs of reaction ratio (No. showing signs / No. dosed)

Dose (g/kg)

0

6.4

8.0

10.0

16.0

Pilo-erection

 

4/4

4/4

4/4

4/4

3/4

Abnormal body carriage

(hunched posture)

0/4

4/4

3/4

4/4

3/4

Abnormal gait

(waddling)

0/4

4/4

3/4

4/4

3/4

Decreased respiratory rate

0/4

4/4

3/4

4/4

3/4

Lethargy

 

0/4

4/4

3/4

4/4

3/4

Pallor of the extremities

0/4

4/4

4/4

4/4

3/4

Increased salivation

 

0/4

4/4

4/4

4/4

3/4

Ataxia

 

0/4

2/4

3/4

3/4

3/4

Ptosis

 

0/4

2/4

3/4

4/4

3/4

Diarrhoea

 

0/4

3/4

0/4

1/4

0/4

Râles

 

0/4

2/4

0/4

2/4

0/4

Diuresis

 

0/4

1/4

2/4

1/4

0/4

Gasping respiration

 

0/4

0/4

1/4

4/4

0/4

Comatose-like condition

0/4

0/4

1/4

1/4

1/4

Facial oedema

 

0/4

0/4

0/4

0/4

2/4

Applicant's summary and conclusion

Interpretation of results:
other: not harmful
Remarks:
In accordance with EU CLP (EC no 1272/2008 and its amendments)
Conclusions:
The acute oral LD50 in rats was determined to be between 6400 and 16000 mg/kg bw in a study performed similar to OECD TG 401.
Executive summary:

A study was performed to assess the acute oral toxicity of the substance to the rat according to a protocol similar to OECD TG 401. A group of four fasted rats (two of each sex) was given a single dose by gavage of the substance, as supplied, at a dose level ranging from 6.4 to 16.0 g/kg bw. All animals were observed for 14 days and necropsied.

Clinical signs observed were ptosis, lethargy, pilo-erection, ataxia, abnormal body carriage, abnormal gait, a decreased respiratory rate, pallor of the extremities and increased salivation. Reduced body weight gains were seen in one male and one female at 6.4 g/kg during the first week of observation and in one female at 10.0 g/kg during the second week of observation, compared to the controls. Body weight gains of the remaining animals were normal throughout the two-week observation period. The acute oral LD50 in rats was determined to be between 6400 and16000  mg/kg bw.

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