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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
10th May 2005 - 12th August 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. Study conducted on middle weight fraction of shale oils.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Identification: Shale oil, middle fraction
Description :Liquid
Batch number: 1
Purity min.: 99 %
Composition: Complex mixture of hydrocarbons and oxygen compounds
Stability of test item: Stable under storage conditions
Expiry date: 04-MAR-2006
Storage conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592, L’Arbresle
- Age at study initiation: 14 weeks (male), 12-13 weeks (females)
- Weight at study initiation: NDA
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 10th May - 17th May 2005

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
- Other: Music was played during the daytime light period.

IN-LIFE DATES: From: 10th May 2005 To: 8th June 2005

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: right eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): N/A

VEHICLE
N/A
Duration of treatment / exposure:
The lids were then gently held together for about one second to prevent loss of test item.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed
- Time after start of exposure: N/A

SCORING SYSTEM:

The ocular reaction (i.e. corneal opacity, iridic effects, conjunctivae and chemosis) was assessed according to the numerical scoring system listed in the Commission Directive 67/548/EEC, at approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, 17 and 21 days after instillation.
Additionally, ocular discharge, reddening of the sclerae and staining of conjunctivae, sclerae and cornea by the test item was assessed according to the scheme given under the commission directive 67/548/EEC.
When present, corrosion was recorded and reported.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.56
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
2.11
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately, insofar as numerical scores were assessable. The individual mean scores for corneal opacity were 1.00, 1.00 and 0.00 and for iris 1.00, 0.67 and 0.00 for all three animals. The individual mean scores for the conjunctivae was 2.00 for all three animals, for reddening and 3.00, 2.00 and 1.33 for chemosis, respectively.
Very slight corneal opacity affecting the whole area was noted in two animals from the 24-hour to the 72-hour reading and persisted in one animal up to the 10-day observation. Reduced light reflex was seen in two animals from the 24- or 48-hour to the 72-hour reading.
Slight to moderate reddening of the conjunctivae was noted in all animals form the 1-hour to the 10-day examination and slight reddening persisted in two animals up to the 17-day reading.
Slight to marked swelling (chemosis) with half-closed lids of the conjunctivae was observed in all animals from the 1-hour to the 72-hour examination and slight swelling persisted up to the 10-day reading in two animals.
Slight to moderate reddening of the sclerae was present in all animals from the 1-hour to the 72-hour observation and slight reddening persisted in two animals up to the 10-day examination, although symptoms of the sclera could not be assessed in one animal 24 hours after treatment due to swelling of the conjunctivae.
Slight to moderate ocular discharge was noted in all animals from 1-hour to the 48-hour reading and slight discharge was still present in two animals at the 72-hour observation and again in one animal at the 10-day reading.
Mucus was present in the eye from the 24- to the 72-hour reading in one animal, whereas this was only noted at the 48-hour observation in another animal.
No abnormal findings were observed in the treated eye of any animal 21 days after treatment, the end of the observation period for all animals.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

No staining of the treated eyes produced by the test item was observed.

No corrosion of the cornea was observed at any of the reading times.

The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean chemosis score of the three animals at the mean of the 24, 48 and 72 hour timepoints was 2.11. Using the referred classification (Commission Directive 2001/59/EC of August 06, 2001), Shale oil is considered to be “irritating” to the rabbit eye on this basis. No other scores reached the threshold for classification.
Executive summary:

The eye irritation potential of shale oils, medium was examined in an experiment according to OECD 404 and performed to GLP. Shale oils, heavy was applied to the torso of 2 female and 1 male New Zealand white rabbit, and held in place with a semi-occlusive dressing for 4 hours. After the exposure, the test substance was washed off and the rabbits were then observed for 14 days.

The mean chemosis score of the three animals at the mean of the 24, 48 and 72 hour timepoints was 2.11. Using the referred classification (Commission Directive 2001/59/EC of August 06, 2001), Shale oil is considered to be “irritating” to the rabbit eye on this basis. No other scores reached the threshold for classification.

Based on the rationale for read-across, it is considered acceptable to use this study to address the same endpoint for the light fraction of shale oil.