Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date 14 March 2017 Experimental completion date 28 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: • Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of Amines, N-tallow alkyltrimethylenedi-, mono(2-ethylhexanoates), Amines, N-tallow alkyltrimethylenedi-, acetates and n-tallow-1,3-diaminopropane ditallate
EC Number:
947-476-4
Molecular formula:
Not applicable, UVCB
IUPAC Name:
Reaction mass of Amines, N-tallow alkyltrimethylenedi-, mono(2-ethylhexanoates), Amines, N-tallow alkyltrimethylenedi-, acetates and n-tallow-1,3-diaminopropane ditallate
impurity 1
Chemical structure
Reference substance name:
Heptane
EC Number:
205-563-8
EC Name:
Heptane
Cas Number:
142-82-5
Molecular formula:
C7H16
IUPAC Name:
heptane
Test material form:
solid
Remarks:
paste
Details on test material:
Batch HJI16-040
Synthesis of sample for testing in heptane.
Residual heptane after drying: 0.5%
Acetic acid: 4.6 % (w/w)
2-ethylhexanoic acid: 10.6 % (w/w)
Tall oil fatty acids 32.2 % (w/w)
Amines, N-tallow alkyltrimethylenedi 52.2 % (w/w)
Specific details on test material used for the study:
Identification: Diamine-Fatty Acids mixture salt
Batch: HJ16-040
Purity: 99.6%
Physical state / Appearance: brown paste
Expiry date: 07 July 2017
Storage conditions: room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
One New Zealand White (Hsdlf:NZW) strain rabbit was supplied by Envigo RMS (UK) Limited, Leicestershire, UK. At the start of the study the animal weighed 3.23 kg and was 12 to 52 weeks old. After an acclimatization period of at least 5 days the animal was given a number unique within the study which was written with a black indelible marker pen on the inner surface of the ear and on the cage label.

Animal Care and Husbandry
The animal was housed in a suspended cage. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °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 and 12 hours darkness.

The animal was 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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
On the day before the test the rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers.
Three suitable sites were selected on the back of the rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
Duration of treatment / exposure:
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
After consideration of the skin reactions produced in the first animal, no additional animals were treated.
Observation period:
14 days
Number of animals:
One
Details on study design:
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.
The results were also evaluated 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.


Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
3-Minute Exposure Period
Well-defined erythema and very slight edema were noted at the treated skin site at the 24 Hour observation with well defined erythema and slight edema noted at the 48 Hour observation and well defined erythema and very slight edema noted at the 72 Hour observation. Slight desquamation was noted at the treated skin site at the 7 Day observation.

The treated skin site appeared normal at the 14-Day observation.

1-Hour Exposure Period
Very slight erythema and very slight edema were noted at the treated skin site immediately and 1 hour after treatment. Well defined erythema and slight edema were noted at the treated skin site at the 24 Hour observation with well defined erythema and very slight edema noted at the 48 and 72 Hour observations. The erythema and edema extended approximately 10 mm around the test site at the 24, 48 and 72 Hour observations.

Additional skin reactions noted at the treated skin site at the 24, 48 and 72 Hour observations were hemorrhage of the dermal capillaries, blanching of the skin, light brown discoloration of the epidermis and loss of skin elasticity and flexibility. A hardened dark brown/black colored scab, preventing accurate evaluation of erythema and edema, was noted at the treated skin site at the 7 Day observation. Small superficial scattered scabs and glossy skin were noted at the treated skin site at the 14 Day observation.

4-Hour Exposure Period
Very slight erythema and slight edema were noted at the treated skin site immediately after patch removal with well defined erythema and slight edema noted 1 hour after treatment. Well defined erythema and moderate edema were noted at the treated skin site at the 24 Hour observation with well defined erythema and slight edema noted at the 48 and 72 Hour observations. The erythema and edema extended approximately 10 mm around the test site at the 24 Hour observation.

Additional skin reactions noted at the treated skin site at the 24, 48 and 72 Hour observations were hemorrhage of the dermal capillaries, blanching of the skin, light brown discoloration of the epidermis and loss of skin elasticity and flexibility. A hardened dark brown/black colored scab, preventing accurate evaluation of erythema and edema, was noted at the treated skin site at the 7 Day observation. Small superficial scattered scabs, scar tissue and glossy skin were noted at the treated skin site at the 14 Day observation.

The skin reactions noted were considered to be irreversible and indicative of full thickness tissue destruction.
Other effects:
The animal showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Rabbit Number and Sex

75729Female

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

Immediately

0

1

1 Hour

0

1

24 Hours

2

2RHdBlLeLfBr

48 Hours

2

2RHdBlLeLfBr

72 Hours

2

2RHdBlLeLfBr

7 Days

0D

?eSt

14 Days

0

0SsG

Edema Formation

Immediately

0

1

1 Hour

0

1

24 Hours

1

2

48 Hours

2

1

72 Hours

1

1

7 Days

0

?od

14 Days

0

0

 

Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Rabbit Number and Sex

75729Female

Erythema/
Eschar Formation

Immediately

1

1 Hour

2

24 Hours

2RHdBlLeLfBr

48 Hours

2HdBlLeLfBr

72 Hours

2HdBlLeLfBr

7 Days

?eSt

14 Days

0SsScG

Edema Formation

Immediately

2

1 Hour

2

24 Hours

3

48 Hours

2

72 Hours

2

7 Days

?od

14 Days

0

Classification                                                      :              CORROSIVE

 

Individual body Weights and Body Weight Change 

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

Day 0

Day 14

75729Female

3.23

3.51

0.28

 


Bl =                Blanching of the skin

Br =       Light brown discoloration of the epidermis

D=          Slight desquamation

G =         Glossy skin

Hd =                      Hemorrhage of dermal capillaries

Le =       Loss of skin elasticity

Lf =       Loss of skin flexibility

R =         Erythema and edema extended approximately 10 mm around the test site

Ss =      Small superficial scattered scabs

St =        Hardened dark brown/black colored scab

?e =        Adverse skin reaction prevented accurate evaluation of erythema

?od =     Adverse skin reaction prevented accurate evaluation of edema

Bl =                Blanching of the skin

Br =       Light brown discoloration of the epidermis

G =         Glossy skin

Hd =                      Hemorrhage of dermal capillaries

Le =       Loss of skin elasticity

Lf =       Loss of skin flexibility

R =         Erythema and edema extended approximately 10 mm around the test site

Sc =       Scar tissue

Ss =      Small superficial scattered scabs

St =        Hardened dark brown/black colored scab

?e =        Adverse skin reaction prevented accurate evaluation of erythema

?od =     Adverse skin reaction prevented accurate evaluation of edema

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
The test item was classified as CORROSIVE to rabbit skin (based on one animal only).

The test item was also classified as Category 1C (Corrosive) according to the Globally Harmonized System of Classification and Labeling of Chemicals.

The test item was also classified as Corrosive (Category 1C) according to Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures. It is reasonable to assume that the signal word “Danger” and the Hazard Statement “H314: Causes severe skin burns and eye damage” are therefore required.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item following single, 3‑Minute, 1 and 4‑Hour, semi‑occluded applications to the intact rabbit skin.

Results

A single 3‑Minute semi-occluded application of the test item to the intact skin of one rabbit produced well-defined erythema, slight edema and slight desquamation. The treated skin site appeared normal at the 14‑Day observation.

A single 1‑Hour semi-occluded application of the test item to the intact skin of one rabbit produced well‑defined erythema, slight edema, hemorrhage of the dermal capillaries, blanching of the skin, light brown discoloration of the epidermis, loss of skin elasticity and flexibility, small superficial scattered scabs, a hardened dark brown/black colored scab (preventing evaluation of erythema and edema) and glossy skin. On occasions the erythematous and edematous reactions extended approximately 10 mm beyond the treatment site.

A single 4‑Hour, semi occluded application of the test item to the intact skin of one rabbit produced reactions indicative of dermal corrosion. The reactions included well‑defined erythema, moderate edema, hemorrhage of the dermal capillaries, blanching of the skin, light brown discoloration of the epidermis, loss of skin elasticity and flexibility, a hardened dark brown/black colored scab (preventing evaluation of erythema and edema), small superficial scattered scabs, scar tissue and glossy skin. On occasions the erythematous and edematous reactions extended approximately 10 mm beyond the treatment site.The skin reactions noted were considered to be irreversible and indicative of full thickness tissue destruction.

Conclusion

The test item was classified as CORROSIVE to rabbit skin (based on one animal only).

The test item was also classified as Category 1C (Corrosive) according to the Globally Harmonized System of Classification and Labeling of Chemicals.

The test item was also classified as Corrosive (Category 1C) according to Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures. It is reasonable to assume that the signal word “Danger” and the Hazard Statement “H314: Causes severe skin burns and eye damage” are therefore required.