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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted methods for a skin irritation study and equivalent or similar to OECD Guideline 404.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted methods for a skin irritation study and equivalent or similar to OECD Guideline 404.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: Primary Irritation Score divided by number of animals
Time point:
other: 72 hours
Score:
0.1
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: The test substance produced a Primary Irritation Index of 0.1 corresponding to a negligible irritation response.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritant / corrosive response data:
No signs of irritation were noted during the study for one animal. Very slight erythema was noted at both application sites of two animals one hour after termination of exposure. For one of these two animals, the very slight erythema persisted at both sites to the 24-hour observation.
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not a primary skin irritant. Only very slight erythema (Grade 1) was seen in one of three animals at the 24-hour observation when the test material was applied to intact skin under semi-occluded contact for four hours. No signs of edema were noted during the study. Complete reversibility of the irritant effect was evident by 48 hours. Based on the results of this study, UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) was not considered to be irritating to rabbit skin, and therefore, presents a low irritation hazard upon skin contact under conditions of normal use. UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not classified for Skin Irritation/Corrosion according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

This data is being read across from the source study that tested Resin acids and Rosin acids, esters with pentaerythritol based on category read across that is explained in the category justification document attached in Section 13 of the dossier.

In a primary dermal irritation study, using the method described in the International Standard ISO 10993-10:1995, Biological Evaluation of Medical Devices-Part 10: Tests for Irritation and Sensitization, Section 5.2 Skin Irritation Test, three male New Zealand white rabbits were dermally exposed to two applications of 0.5 gram of UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) for 4 hours under semi-occluded contact to intact skin. Animals were then observed for 72 hours. No edema was observed during the study. No signs of irritation were noted during the study for one animal. Very slight erythema was noted at the application site of two animals one hour after termination of exposure. For one of these two animals, the very slight erythema persisted to the 24-hour observation. The irritation response was completely reversible by 48 hours. The test substance produced individual Primary Irritation Scores of 0.0, 0.0, and 0.3 for the three animals tested and a Primary Irritation Index of 0.1 (negligible irritation). UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not considered a dermal irritant in this study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Name (according to study report): UNITAC RLM
-Batch Number: 98-0257
-Physical state: straw colored pellets
-Storage: approximately -18 °C in the dark under nitrogen
-Date test material received: 1998-04-30
-The test substance was ground to a fine powder prior to application.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS:
-Source: David Percival Ltd., Moston, Sandbach, Chesire, UK
-Animals: 3 males
-Age: approximately 12-16 weeks old
-Quarantine period: 5 days
-Weight at Study Initiation: 2.69-2.89 kg
-Housing: Individually in suspended, metal cages
-Diet: STANRAB SQC Rabbit Diet, Special Diets Services, Ltd, Witham, Essex (UK) available ad libitum
-Water: drinking water available ad libitum
-Identification method: each animal was assigned 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
-Method of Animal Distribution: no data

ENVIRONMENTAL CONDITIONS:
-Room temperature (°C): maintained at 18-21
-Relative humidity (%): maintained at 59-63
-Light: 12 hour light/dark cycle
-Rate of air exchange: 15 changes/hour

IN-LIFE DATES:
-Date of experiment initiation: 1998-05-12
-Date of experiment termination: 1998-05-15

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: Dorsal/flank area clipped free of hair. Two application sites (left and right) were used for each animal.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 gram
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
The method used followed the recommendations of the International Standard ISO 10993-10: 1995, Biological Evaluation of Medical Devices-Part 10: Tests for Irritation and Sensitization, Section 5.2 Skin Irritation Test.

Three rabbits were clipped free of hair from the dorsal flank area approximately 24 hours prior to exposure of the test substance. Two application sites (left & right) were identified for each animal. For each site, a dose of 0.5 gram of the test substance was moistened with 0.6 mL distilled water and then applied to a 2.5 cm x 2.5 cm cotton gauze patch. The gauze patch was placed on the application site of each rabbit and secured with a strip of surgical tape (BLENDERM). The trunk of each rabbit was then wrapped with an elasticated corset (TUBIGRIP). After a 4-hour exposure period, the corset and patches were removed from each rabbit and any residual material was removed by gentle swabbing with cotton wool soaked in distilled water. At 1, 24, 48, and 72 hours after termination of exposure, the application sites were examined for evidence of primary irritation and scored according to the 4-point scale from Draize (1977). The scores for erythema and edema at the 24-, 48-, and 72-hour readings were totalled for each animal, and divided by the total number of observations (six: two at each time point), resulting in a primary irritation score for each animal. The three primary irritation scores were added together and divided by the number of animals to give a Primary Irritation Index (PII). The PII was used to classify the test substance according to the following scheme:

Primary Irritation Index
0.0-0.4 = Negligible response
0.5-1.9 = Slight response
2.0-4.9 = Moderate response
5.0-8.0 = Severe response

Reference:
Draize, JH (1977) "Dermal and Eye Toxicity Tests," In: Principles and Procedures for Evaluating the Toxicity of Household Substances. National Academy of Sciences, Washington, DC

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: Primary Irritation Score divided by number of animals
Time point:
72 h
Score:
0.1
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: The test substance produced a Primary Irritation Index of 0.1 corresponding to a negligible irritation response.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritant / corrosive response data:
No signs of irritation were noted during the study for one animal. Very slight erythema was noted at both application sites of two animals one hour after termination of exposure. For one of these two animals, the very slight erythema persisted at both sites to the 24-hour observation.

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not a primary skin irritant. Only very slight erythema (Grade 1) was seen in one of three animals at the 24-hour observation when the test material was applied to intact skin under semi-occluded contact for four hours. No signs of edema were noted during the study. Complete reversibility of the irritant effect was evident by 48 hours. Based on the results of this study, UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) was not considered to be irritating to rabbit skin, and therefore, presents a low irritation hazard upon skin contact under conditions of normal use. UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not classified for Skin Irritation/Corrosion according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

In a primary dermal irritation study, using the method described in the International Standard ISO 10993-10:1995, Biological Evaluation of Medical Devices-Part 10: Tests for Irritation and Sensitization, Section 5.2 Skin Irritation Test, three male New Zealand white rabbits were dermally exposed to two applications of 0.5 gram of UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) for 4 hours under semi-occluded contact to intact skin. Animals were then observed for 72 hours. No edema was observed during the study. No signs of irritation were noted during the study for one animal. Very slight erythema was noted at the application site of two animals one hour after termination of exposure. For one of these two animals, the very slight erythema persisted to the 24-hour observation. The irritation response was completely reversible by 48 hours. The test substance produced individual Primary Irritation Scores of 0.0, 0.0, and 0.3 for the three animals tested and a Primary Irritation Index of 0.1 (negligible irritation). UNITAC RLM (Resin acids and Rosin acids, esters with pentaerythritol) is not considered a dermal irritant in this study.