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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
The study was performed between 21 September 2011 and 12 October 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study on a read-across substance, conducted in compliance with agreed protocols, with no deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 26 June 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
IUPAC Name:
Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
Test material form:
liquid: viscous
Details on test material:
Sponsor's identification: Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts
CAS number : 68140-11-4
Identifier : TIS O2779
Description : brown extremely viscous liquid
Batch number : LE012569
Date received : 07 June 2011
Expiry date : 06 June 2013
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: Eight to twelve weeks of age.
- Weight at study initiation: At the start of the study the animals weighed at least 200g. The weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study: None.
- Housing: 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 up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access to food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
For the purposes of the study the test item was weighed out according to each animals individual bodyweight.
Details on dermal exposure:
TEST SITE:
On the day before treatment the back and flanks of each animal were clipped free of hair.

In the absence of data suggesting the test item was toxic, one male and one female rat were initially treated with the test item at a dose level of 2000 mg/kg.

The appropriate amount of test item 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 and for the remainder of the test. 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 bodyweight to give a total of five males and five females. 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.

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females at 2000 mg/kg bodyweight.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
The animals were observed for deaths or overt signs of toxicity at ½, 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 and scored according to the Draize scale (see evaluation of skin reactions).

Any other skin reactions, if present were also recorded.

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

- Necropsy of survivors performed: yes
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.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at the limit dose: 95% confidence limits not reported.
Mortality:
There were no deaths.


Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Table 4.
Animals showed expected gains in bodyweight over the study period, except for three animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Other findings:
Dermal Reactions:
Signs of dermal irritation noted were light brown discolouration of the epidermis, small superficial scattered scabs, hardened light brown or dark brown/black coloured scab, scab lifting to reveal glossy skin, scab lifting at edges to reveal dried blood, scab cracking, scab undulating, loss of skin elasticity and flexibility and glossy skin. Adverse reactions prevented accurate evaluation of erythema and oedema at the test sites of nine animals.

Any other information on results incl. tables

Individual clinical observations and mortality data are given in Table 1.

Individual Clinical Observations and Mortality Data

Dose Level

mg/kg bw

Animal Number and Sex

Effects Noted After Initiation of Exposure (Hours)

Effects Noted After Initiation of Exposure (Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3

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

4-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-3

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 Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Change (g) During Week

0

7

14

1

2

2000

1-0 Male

253

243

269

-10

26

3-0 Male

236

239

242

3

3

3-1 Male

237

241

250

4

9

3-2 Male

276

284

293

8

9

3-3 Male

277

279

283

2

4

2-0 Female

216

210

219

-6

9

4-0 Female

201

216

220

15

4

4-1 Female

220

226

231

6

5

4-2 Female

204

204

208

0

4

4-3 Female

214

210

216

-4

6

Table 5              Individual Necropsy Findings

Dose Level

mg/kg bw

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 bodyweight.
The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.
Executive summary:

. The study was performed to assess the acute dermal toxicity of the read-across substance [Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts] in the rat, according to OECD 402. Initially, two animals (one male and one female) were given a single, 24-hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. Signs of dermal irritation noted were light brown discolouration of the epidermis, scabbing, scab lifting to reveal glossy skin or dried blood, scab cracking, scab undulating, loss of skin elasticity and flexibility and glossy skin. Adverse reactions prevented accurate evaluation of erythema and oedema at the test sites of nine animals. Animals showed expected gains in bodyweight over the study period, except for three animals which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.  The acute dermal median lethal dose (LD50) of the test material in the rat was found to be greater than 2000 mg/kg bodyweight.

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