Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 30 October 2013 and 13 November 2013.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was considerd to be a reliability 1 as it has been conducted according to OECD Test Guideline 402 using a fixed dose method and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Identification: IFF TM 10-202
Storage Conditions: Room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 five 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 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, 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. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve 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:
On the day before treatment the back and flanks of each animal were clipped free of hair.
Using available information on the toxicity of the test item, a single group of animals was treated with 2000 mg/kg (specific gravity 0.882; dose volume 2.27 mL/kg).
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 for the 24-Hour exposure period.
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. The animals were returned to group housing for the remainder of the study period.

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 h
Doses:
Single dose
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation
Any other skin reactions, if present were also recorded.
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:
No abnormalities were noted at necropsy.
Other findings:
Signs of dermal irritation noted at the treatment sites of four females were very slight to well-defined erythema, very slight edema small superficial scattered scabs and crust formation. Slight desquamation was also noted at the treatment sites of three females.
No signs of dermal irritation were noted at the treatment sites of all males and one female.

Any other information on results incl. tables

Individual clinical observations and mortality data with dose level at 2000 mg/kg

Animal No. & Sex

Effects noted after dosing (hours)

Effects noted during period after dosing

(Days)

0.5

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1-0 male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1 male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2 male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3 male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4 male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4 female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = No signs of systemic toxicity.

Individual dermal reactions - Males (Dose level 2000 mg/kg)

Animal No & Sex

Observation

Effects noted during period after dosing

(Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1-0 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

1-1 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

1-2 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

1-3 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

1-4 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

0 = No reactions.

Individual dermal reactions - Females (Dose level 2000 mg/kg)

Animal No & Sex

Observation

Effects noted during period after dosing

(Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2-0 female

Erythema

0

1

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

D

CFSs

CFSs

CFSs

Ss

Ss

0

0

0

0

0

2-1 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

2-2 female

Erythema

0

2

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

DCf

D

D

CfSs

Ss

CfSs

Ss

0

0

0

0

0

0

2-3 female

Erythema

0

1

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

Ss

Ss

SsCf

Ss

Ss

0

0

0

0

0

2-4 female

Erythema

0

2

1

1

1

1

0

0

0

0

0

0

0

0

Edema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

D

D

CfSs

CfSs

CfSs

Ss

0

0

0

0

0

0

0 = No reactions D = Slight desquamation Ss = Small superficial scattered scabs Cf = Crust formation 

Individual body weights and body weight changes (Dose level 2000 mg/kg)

Animal No. & Sex

Body weight (g) at Day

Body Weight Change

0

7

14

1

2

1-0 Male

290

308

332

18

24

1-1 Male

253

262

284

9

22

1-2 Male

275

284

302

9

18

1-3 Male

269

281

300

12

19

1-4 Male

264

286

304

22

18

2-0 Female

230

233

240

3

7

2-1 Female

233

241

246

8

5

2-2 Female

233

237

242

4

5

2-3 Female

224

228

236

4

8

2-4 Female

228

240

244

12

4

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

The acute dermal toxicity potential of the test material, IFF TM 10-202, gave an LD50 of > 2000 mg/kg body weight according to OECD Test Guideline 402, using a fixed dose method.