Registration Dossier

Administrative data

Description of key information

Scaling was seen on the skin of all three rabbits at the 72 hour observation time, 
and 2 animals at the end of the 14 day observation period. It is therefore irritating
to the skin of rabbits (this result is read-across from Shale oil middle fraction).
The mean chemosis score from the 24, 48 and 72 hour time periods was 2.11. It is
therefore irritating to the eyes of rabbits (this result is read-across from Shale oil
middle fraction).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
26th April - 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.
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
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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: 26th April - 2nd 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: 26th April 2005 To: 17th May 2005
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml shale oil
- Concentration (if solution): N/A

VEHICLE
N/A
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: NDA
- Type of wrap if used: Shale oil was placed on a surgical gauze patch. This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with luke warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM:

The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, approximately 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after the removal of the dressing, gauze patch and test item.
To allow further examination of the test site, one animal was re-clipped on completion of the 10-day examination.
If evident, corrosive or staining properties of the test item were described and recorded.
Irritation parameter:
erythema score
Basis:
animal: 28
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal: 29
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal: 30
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal: 28
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal: 29
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal: 30
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 2.00, 1.00 and 2.00, respectively and the mean oedema score was 1.00 for all three animals, respectively. (see table 1)
Very slight to well-defined erythema were noted in all animals from the 1- to the 72-hour reading and very slight erythema persisted in two animals up to the 7-day examination.
Very slight swelling was observed in all animals from the 24- to the 72-hour reading and persisted in two animals up to the 7-day examination.
Scaling was noted in all animals from the 72-hour reading to the 10-day examination or to the end of the observation period.
No abnormal findings were observed on the treated skin of any animal 14 days after treatment except scaling, which was present in two animals from the 72-hour reading to the end of the observation time.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Slight brown staining produced by the test item of the treated skin was observed in all animals from the 1-hour reading up to the 7- or 10-day examination, respectively.

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

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

COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004

Grading of Skin Reactions

ERYTHEMA AND ESCHAR FORMATION

No erythema.......................................................................................................................0

Very slight erythema............................................................................................................1

Well-defined erythema........................................................................................................2

Moderate to severe erythema.............................................................................................3

Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading.................................................4

OEDEMA FORMATION

No oedema.........................................................................................................................0

Very slight oedema (barely perceptible)...............................................................................1

Slight oedema (edges of area well-defined by definite raising)...............................................2

Moderate oedema (edges raised approximately 1 mm).........................................................3

Severe oedema (raised more than 1 mm and extending beyond the area of exposure)............4

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean scores of the three rabbits combined at the mean of the 24, 48 and 72 hour time points was 1.67 for erythema and 1 for oedema. Scaling was present in all three animals at 72 hours, and still present in two at the end of the 14 day observation period. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Shale oil is considered to be “irritating” to rabbit skin with respect to the scaling effects observed.
Executive summary:

The skin 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 scores of the three rabbits combined at the mean of the 24, 48 and 72 hour time points was 1.67 for erythema and 1 for oedema. Scaling was present in all three animals at 72 hours, and still present in two at the end of the 14 day observation period. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Shale oil is considered to be “irritating” to rabbit skin with respect to the scaling effects observed.

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
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.
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
GLP compliance:
yes (incl. QA statement)
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
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The skin irritation potential of shale oils, middle fraction was examined in an experiment according to OECD 404 and performed to GLP. Shale oils, medium was applied to the torso of 2 female and 1 male New Zealand white rabbits, 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 scores of the three rabbits combined, averaging the 24, 48 and 72 hour time points were 1.67 for erythema and 1 for oedema. Scaling was present in all three animals at 72 hours, and still present in two at the end of the 14 day observation period. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Shale oil is considered to be “irritating” to rabbit skin with respect to the scaling effects observed.


 


The eye irritation potential of shale oils, middle fraction was examined in an experiment according to OECD 405 and performed to GLP. Shale oils, medium was applied by instillation into the left eye of 2 female and 1 male New Zealand white rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14 and 21 days after instillation.


The mean chemosis score of the three animals averaging the 24, 48 and 72 hour time points 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 these studies to address the same endpoint for the light fraction of shale oil.


 


No specific data on corrosivity of the registered substance are available however, studies evaluating the irritating potential showed signs of irritation for both the skin and eyes, but no corrosive effects. On this basis it can be concluded that the registered substance is not corrosive.



Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based upon the findings of the available studies shale oils light fraction would be classified as a category 2 skin and eye irritant according to Regulation (EC) No 1272/2008. However, to take account of the potential variability in the composition of the UVCB starting material, and the potential variation in the composition of the UVCB substance in scope of this registration, the worst case classification of H314 (Causes severe skin burns and eye damage) and H335 (May cause respiratory irritation) is applied.


For further information, please refer to the document 'Shale oils RAAF Report' as included in section 13.