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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 25 February 2015 and 18 March 2015.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is considered to be a reliability 1 as it has been conducted according to OECD Test Guideline 402 using a standard acute method and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of (5R)-octahydro-1H-4,7-methanoinden-5-ylacetaldehyde and (5S)-octahydro-1H-4,7-methanoinden-5-ylacetaldehyde
EC Number:
940-300-7
Cas Number:
1339119-15-1
Molecular formula:
C12H18O
IUPAC Name:
Reaction mass of (5R)-octahydro-1H-4,7-methanoinden-5-ylacetaldehyde and (5S)-octahydro-1H-4,7-methanoinden-5-ylacetaldehyde
Test material form:
other: Liquid
Details on test material:
Identification (trade name): IFF TM 11-213 (FRET 09-0425)
Chemical (IUPAC) name of multi constituent: Reaction mass of 4,7-Methano-1H-indene-5-acetaldehyde, octahydro- and 4,7-Methano-1H-indene-5-carboxaldehyde, octahydro-6-methyl-
Physical state / Appearance: clear colorless liquid
Expiry date: 01 July 2015
Storage Conditions: approximately 4 °C in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were 8 to 12 weeks of age. However, the initial female animal was slightly below the minimum weight of 200g specified in the General Study Plan but this was considered not to affect the purpose or integrity of the study. The weight variation did not exceed ±20% of the mean weight for each sex, except for one male which was slightly outside the range. This deviation was considered not to affect the purpose or integrity of the study

The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The initial two animals were housed individually throughout the study. The further group of eight animals (four male and four female) were housed individually during the 24 Hour exposure period and in groups of four, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test Item Formulation and Experimental Preparation
For the purpose of the study the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

The absorption of the test item was not determined.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 / sex / dose
Control animals:
no
Details on study design:
Procedure
On the day before treatment the back and flanks of each animal were clipped free of hair.

The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually throughout the study. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24 Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.

As no mortalities were noted a further group of animals (four males and four females) was similarly treated with the test item at a dose level of 2000 mg/kg body weight to give a total of five males and five females. The animals were caged individually for the 24 Hour exposure period. After the 24 Hour contact period the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item. These animals were returned to group housing for the remainder of the test period.

The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.

After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored.

Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
Very slight erythema was noted at the test sites of six animals from Day 3 up to Day 6. There were no signs of dermal irritation noted at the test sites of the remaining four animals.

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Individual Dermal Reactions - Males

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

Erythema

0

0

1

1

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Male

Erythema

0

0

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Male

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3

Male

Erythema

0

0

1

1

1

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0= No reactions                   1 = Very slight erythema

Individual Dermal Reactions - Females

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

Erythema

0

0

1

1

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-0

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-1

Female

Erythema

0

0

1

1

1

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-2

Female

Erythema

0

0

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-3

Female

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0= No reactions                   1 = Very slight erythema

Individual Body Weights and Body Weight Changes

Dose Level mg/kg

Animal Number and Sex

Body Weight (g) at Day

Body Weight Change (g) During Week

0

7

14

1

2

2000

1-0 Male

228

234

251

6

17

3-0 Male

256

269

287

13

18

3-1 Male

280

291

306

11

15

3-2 Male

249

260

275

11

15

3-3 Male

268

281

297

13

16

2-0 Female

193

201

207

8

6

4-1 Female

208

209

214

1

5

4-2 Female

216

219

223

3

4

4-3 Female

215

217

221

2

4

4-4 Female

201

203

207

2

4

 

Individual Necropsy Findings

Dose Level

mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0

Male

Killed Day 14

No abnormalities detected

3-0

Male

Killed Day 14

No abnormalities detected

3-1

Male

Killed Day 14

No abnormalities detected

3-2

Male

Killed Day 14

No abnormalities detected

3-3

Male

Killed Day 14

No abnormalities detected

2-0

Female

Killed Day 14

No abnormalities detected

4-0

Female

Killed Day 14

No abnormalities detected

4-1

Female

Killed Day 14

No abnormalities detected

4-2

Female

Killed Day 14

No abnormalities detected

4-3

Female

Killed Day 14

No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.
Executive summary:

The acute dermal toxicity of the test substance, TM 11-213, was assessed according to OECD Test Guideline 402 using a standard acute method. The acute dermal median lethal dose (LD50) of the test item was found to be > 2000 mg/kg body weight.