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Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 July - 07 August 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

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

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), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics
IUPAC Name:
Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics
Constituent 2
Chemical structure
Reference substance name:
Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics
EC Number:
940-727-9
Cas Number:
1437281-03-2
Molecular formula:
C12H26 to C15H32
IUPAC Name:
Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics
Test material form:
other: Clear colourless liquid
Details on test material:
- Name of test material (as cited in study report): Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics
- Substance type: Clear colourless liquid
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: From: 09 July - 07 August 2014

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
Single application.
Observation period:
14 days.
Number of animals:
3 males.
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of skin irritation observed in the first animal.

TEST SUBSTANCE PREPARATION
The test substance was applied undiluted as delivered by the sponsor.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and/or 7 days and/or 14 days after the removal of the dressings and test substance. Readings were done under true light using Philips Master TL-5 HO 49 watt/840. 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.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Irritation: Four hours exposure to 0.5 mL of Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined erythema and slight oedema in the treated skin areas of the three rabbits. Scaliness was noted for one animal, 7 days after exposure. The skin irritation had completely resolved within 72 hours, 7 days or 14 days after exposure.

Corrosion: There was no evidence of a corrosive effect on the skin.
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 symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
An in vivo skin irritation/corrosion study with Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics in the rabbit was conducted based on the OECD 404 test guideline. Rabbits were exposed skin for 4 hours using a semi-occlusive dressing to the test material and evaluated at 1, 24, 48 and 72 hours and/or 7 and/or 14 days after exposure. Exposure to Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics resulted in well defined erythema and slight oedema in the treated skin areas of the three rabbits. Scaliness was noted for one animal, 7 days after exposure. The skin irritation had completely resolved within 72 hours, 7 days or 14 days after exposure. Based on these results Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics does not have to be classified for skin irritation according to the GHS.
Executive summary:

Primary skin irritation/corrosion study with Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics in the rabbit (4-hour semi-occlusive application).

 

The study was carried out based on the guidelines described in:

OECD No.404, "Acute Dermal Irritation/Corrosion" (2002)

EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"

US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

JMAFF Guidelines (2000), including the most recent revisions.

 

Three rabbits were exposed to 0.5 mLof Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and/or 7 and/or 14 days after exposure.

 

Exposure to Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined erythema and slight oedema in the treated skin areas of the three rabbits. Scaliness was noted for one animal, 7 days after exposure. The skin irritation had completely resolved within 72 hours, 7 days or 14 days after exposure.

 

Based on these results Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics 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 (2011)(including all amendments),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).