Registration Dossier

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:
From August 26, 2016 to October 05, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
but the study integrity was not adversely affected by the deviation
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
but the study integrity was not adversely affected by the deviation
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
but the study integrity was not adversely affected by the deviation
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000
Version / remarks:
including the most recent partial revisions
Deviations:
yes
Remarks:
but the study integrity was not adversely affected by the deviation
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: paste like
Details on test material:
- Name of test substance (as cited in study report): Phosphoric acid, mono- and di-isotridecyl esters, potassium salts
- Batch: RE 7-8
- Appearance: paste-like
Specific details on test material used for the study:
Batch no.: Re 7-8
Purity/composition: 95.85%
Appearance: white waxy solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Recognized by international guidelines as the recommended test system (e.g. EC, OECD)
Details on test animals and environmental conditions:
Source: Charles River France, L’Arbresle Cedex, France
Acclimatization period: at least 5 days before start of treatment under laboratory conditions
Number of animals: 3 males.
Age and body weight: at start of dosing, the animals were between 12 and 24 weeks old and body weights were at least 1.5 kg
Temperature 18 to 24°C and Relative humidity: 40 to 70% with a 12-hour light/12-hour dark cycle.
Diet: pelleted diet for rabbits, approximately 100g per day. Hay and wooden sticks were available during the study period
Water: free access to tap water

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4h
Observation period:
14d
Number of animals:
3
Details on study design:
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations. Each animal was treated by dermal application of 0.5g of the test substance for 4 hours using a semi-occlusive dressing. The test substance was moistened with 0.5 mL of the vehicle and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: at all time points
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24/48/72h and 7d
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 14d
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 72h
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: at all time points
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/48/72h and 7d
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 14d
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 7d
Remarks on result:
positive indication of irritation
Remarks:
very slight or well-defined
Irritant / corrosive response data:
- Exposure to the test substance resulted in very slight or well-defined erythema and very slight or well-defined oedema in the treated skin areas of the three rabbits, which had resolved within 7 days after exposure in one animal, within 14 days after exposure in another animal and persisted until termination in the remaining animal. There was no evidence of a corrosive effect on the skin.
- Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Other effects:
- Coloration / remnants: no staining of the treated skin by the test substance was observed and no test substance remnants were seen.
- Toxicity / mortality: no signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. The body weight was not modified by the treatment.

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Remarks:
not classified
Conclusions:
Under the study conditions, the test substance was considered to be not irritating to rabbit skin.
Executive summary:

An in vivo study was conducted to determine the skin irritation potential of the test substance according to OECD Guideline 404, EU Method B.4, EPA OPPTS 870.2500 and Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, in compliance with GLP. Three male New-Zealand white rabbits were used in this experiment. Approximately 24 h before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm). Each animal was treated by dermal application of 0.5 g of the test substance for 4 h using a semi-occlusive dressing. The test substance was moistened with 0.5 mL of the vehicle and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. 4 h after the application, the dressing was removed and the skin cleaned of residual test substance using tap water. Skin reactions were assessed 1, 24, 48 and 72 h and 7 and 14 d after exposure. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls. The irritation was assessed according to the standard numerical scoring system. At each observation, the highest scores given were recorded. Mortality/viability was assessed twice daily. Toxicity was recorded at least once daily. Body weight were measured on the day of treatment (prior to application) and on the day of the final observation. No histopathology was performed. Exposure to the test substance resulted in very slight or well-defined erythema and very slight or well-defined oedema in the treated skin areas of the three rabbits, which had resolved within 7 d after exposure in one animal, within 14 d after exposure in another animal and persisted until termination in the remaining animal. There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed and no test substance remnants were seen. No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. The body weight was not modified by the treatment. Under the study conditions, the test substance was considered to be not irritating to rabbit skin (van Huigevoort, 2016).