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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 July - 08 August 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
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 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye 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, C18-C24, isoalkanes, <2% aromatics
IUPAC Name:
Hydrocarbons, C18-C24, isoalkanes, <2% aromatics
Constituent 2
Chemical structure
Reference substance name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics
EC Number:
940-734-7
Molecular formula:
C18H38, C19H40, C20H42, C21H44, C22H46, C23H48, C24H50
IUPAC Name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics
Test material form:
other: Clear colourless liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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: 14 July - 08 August 2014

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount applied: 0.1 mL
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
Number of animals or in vitro replicates:
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 eye irritation observed in the first animal.

TREATMENT
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the 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.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 405.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Irritation: Instillation of 0.1 mL of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in all animals. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion: There was no evidence of ocular corrosion.
Other effects:
Colouration/Remnants: No staining of (peri) ocular tissues 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
Conclusions:
In vitro and in vivo eye irritation studies were conducted with Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (GS310) in accordance with OECD test guidelines 437 and 405, respectively, and in compliance with GLP. The BCOP test did not indicate an irritancy potential based on either the opacity or permeability endpoints. In the in vivo study, a single instillation of the test substance in three rabbits resulted in redness and discharge in all animals one hour after dosing. The effects were fully resolved 24 hours post-instillation. The results of the studies indicated that the substance does not require classification for skin irritation according to the relevant EC and GHS criteria.
Executive summary:

Acute eye irritation/corrosion study with Hydrocarbons, C18-C24, isoalkanes, <2% aromatics in the rabbit.

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

OECD No.405 (2012) "Acute Eye Irritation / Corrosion"

EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

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

 

Single samples of 0.1 mL of Hydrocarbons, C18-C24, isoalkanes, <2% aromatics were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in all animals.

 

Based on these results, Hydrocarbons, C18-C24, isoalkanes, <2% aromatics does not have to be classified and has no obligatory labelling requirement for eye 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).