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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 September 2017 - 10 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of 7,7-dimethyl-2-methylidenebicyclo[2.2.1]heptane and (1R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane and (1S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane and (1S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
Molecular formula:
not applicable, multiconstituent substance
IUPAC Name:
Reaction mass of 7,7-dimethyl-2-methylidenebicyclo[2.2.1]heptane and (1R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane and (1S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane and (1S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan: WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 173.8 to 201.8 g
- Fasting period before study: overnight prior to dosing until three hours post-dosing
- Housing: 3 females in polypropylene rat cages covered with stainless steel grid top. Autoclaved clean rice husk was used as the bedding material. Wooden blocks were provided as enrichment material.
- Diet (e.g. ad libitum): Ad libitum. Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA. The quality of feed is regularly monitored at Jai Research Foundation.
- Water (e.g. ad libitum): Ad libitum. UV sterilized water filtered through Reverse Osmosis water filtration system. The quality of water is regularly monitored at Jai Research Foundation.
- Acclimation period: 6 to 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 57 to 67%
- Air changes (per hr): At least 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours contimuous light (06.00 to 18.00 h) and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.4 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: without preliminary information, the selected starting dose is 300 mg/kg body weight.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: toxicity and mortality at 30 min, 1h, 2 h, 3h, 4h, 6 h after adminitration. Morbidity and mortality twice a day and clinical sings daily during 14 days. Weighing= D0 (prior to dosing) then on D7, and D14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed.
- Other examinations performed:
Clinical observations: evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects and central nervous system effects, behavioural pattern, somatomotor activity and observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical sign was observed in rats treated with 300 and 2000 mg/kg body weight.
Body weight:
Normal gain in body weight was observed in all the rats treated with 300 and 2000 mg/kg body weight.
Gross pathology:
External and visceral examination of terminally sacrificed rats did not reveal any abnormality.

Any other information on results incl. tables

Table 1: Mortality

Dose

(mg/kg body weight)

Set

Number of Rats Used

Mortality after Dosing

At Hour

On Day

0.5 - 4

6

1

2

3

4 - 7

8 - 14

300

I

3

0

0

0

0

0

0

0

II

3

0

0

0

0

0

0

0

2000

III

3

0

0

0

0

0

0

0

IV

3

0

0

0

0

0

0

0

Table 2: Individual and Mean Body Weight (g) and Body WeightChange (%)

Dose

(mg/kg body weight)

Rat

Volume of Dose Administered (mL)

Body Weight (g) on Day

Percent Body Weight Change on Day

 

 

 

0

7

14

7

14

300

1

0.06

186.8

209.6

225.3

12.2

20.6

 

2

0.07

188.1

219.8

230.8

16.9

22.7

 

3

0.06

183.4

204.5

218.4

11.5

19.1

 

Mean

 

186.1

211.3

224.8

13.5

20.8

 

Standard Deviation (±)

 

2.4

7.8

6.2

2.9

1.8

 

4

0.07

191.1

216.6

224.8

13.3

17.6

 

5

0.07

201.1

236.8

247.9

17.8

23.3

 

6

0.06

186.7

214.2

227.4

14.7

21.8

 

Mean

 

193.0

222.5

233.4

15.3

20.9

 

Standard Deviation (±)

 

7.4

12.4

12.7

2.3

3.0

2000

7

0.47

201.8

212.8

228.8

5.5

13.4

 

8

0.43

187.3

204.5

223.6

9.2

19.4

 

9

0.43

184.5

203.8

218.5

10.5

18.4

 

Mean

 

191.2

207.0

223.6

8.4

17.1

 

Standard Deviation (±)

 

9.3

5.0

5.2

2.6

3.2

 

10

0.41

176.0

190.4

205.6

8.2

16.8

 

11

0.40

173.8

188.8

193.8

8.6

11.5

 

12

0.42

182.4

199.0

201.5

9.1

10.5

 

Mean

 

177.4

192.7

200.3

8.6

12.9

 

Standard Deviation (±)

 

4.5

5.5

6.0

0.5

3.4

Key: Day 0 = Before dosing

Applicant's summary and conclusion

Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off may be considered to be 5000 mg/kg body weight by oral route in the rat.
Executive summary:

The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 12 female Wistar rats divided in 4 groups were administered sequentially with test item by oral gavage. The first set of 3 female rats was given a single dose of 300 mg/kg body weight. No mortality was observed at this dose level, so the second set of 3 female rats was treated at the same dose level. No mortality was observed at this dose level, so the third set of 3 female rats was treated at the higher dose level of 2000 mg/kg bw. As no mortality was observed at this dose level, the fourth set of 3 female rats was treated at the same dose level of 2000 mg/kg bw. The body weight evolution of the animals remained normal during the study. No clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be 5000 mg/kg body weight by oral route in the rat.