Registration Dossier

Administrative data

Description of key information

Skin irritation in vivo, rabbit: Burnt Oil Shale(BOS)-P.1082 and Burnt Oil Shale(BOS)-P.-1183: not irritating
Eye irritation in vitro: Burnt Oil Shale(BOS)-P.1082: irritating; Burnt Oil Shale(BOS)-P.1183: not irritating
Read across with Fluidized Bed Combustion (FBC) Fly Ash for Burnt Oil Shale(BOS)-P.1183 in vivo eye irritation, rabbit: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-03-09 - 2010-07-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No 440/2008, L 142, Annex Part B, 30 May 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, D-97633 Sulzfeld
- Age at study initiation: approximately 15 weeks old
- Weight at study initiation: > 2 kg
- Housing: Semi-barrier in an air-conditioned room, housed in ABS - plastic rabbit cages, floor 4200 cm²
- Diet: Free access to autoclaved hay and toAltromin 2123 maintenance diet for rabbits (lot no. 0748), rich in crude fibre
- Water: Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: test item was moistened with aqua ad injectionem (B. Braun Melsungen, lot no. 7494A191, expiry date: 11/2010)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A dose of 0.5 g of the test item was applied to each test site.
Duration of treatment / exposure:
The test item was held in contact with the skin throughout a 4-hour period.
Observation period:
All animals were observed for 72 hours after the patch removal.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: small skin area (approx. 6 cm²) on the left side of the dorsal area
- Type of wrap if used: gauze was held in place with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported

SCORING SYSTEM: Draize system

Irritation parameter:
erythema score
Basis:
mean
Remarks:
3/3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
3/3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
The test item showed neither irritant nor corrosive effects on the intact skin of 3 female rabbits (strain NZW) after a contact time of 4 hours.
Neither mortalities nor significant clinical signs of toxicity were observed.

Absolute body weights in kg

Animal number

Start of study (weight kg)

End of study (weight kg)

1

2.9

3.0

2

3.1

3.2

3

3.3

3.2

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

A GLP - guideline study according to OECD 404 was performed. Under the conditions of the present study, single dermal application of the test item Oil shale, thermal processing waste to rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Neither mortalities nor significant clinical signs of toxicity were observed. In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC and Annex I of Regulation (EC) 1272/2008, the test item Oil shale, thermal processing waste does not have to be classified and has no obligatory labelling requirement for skin irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-03-09 - 2010-04-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
other: isolated corneas from bovine
Strain:
not specified
Details on test animals or tissues and environmental conditions:
not applicable
Vehicle:
physiological saline
Controls:
other: 3 corneas as negative controls treated with physiological saline 0.9% NaCl; 3 corneas as positive control treated with Imidazole 20%
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 20%

VEHICLE
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 0.9%
- Lot/batch no. (if required): 9271A123
- Expiry date: 05-2012
Duration of treatment / exposure:
4 hours
Observation period (in vivo):
not required
Number of animals or in vitro replicates:
other:
3 corneas for the test item were used
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 4 hours incubation at 3 times with MEM (containing phenol red). Once the media was free of the test substance, the cornea was finally rinsed with Complete RPMI (without phenol red)
- Time after start of exposure: after 4 hours ± 5 min

SCORING SYSTEM:
- The following formula was used to determine the in vitro score:
In vitro score = Mean Opacity Value + (15 x Mean OD490 Value)

TOOL USED TO ASSESS SCORE:
1.) After removing the test substance, the opacity measurement was performed
2.) After opacity measurement the medium was removed from the chambers of the holder. The posterior chamber was refilled with fresh Complete RPMI and 1 mL of 5 mg/mL sodium fluorescein was added to the anterior chamber and the corneas were incubated for 90 min at 32 ± 1°C. Then the medium was removed from the posterior chamber and its optical density at 490 nm (OD490) determined, using a spectrophotometer.

Evaluation of the BCOP assay:

Mean score Evaluation
0 – 3 Non irritant
3.1 – 25 Mild irritant
25.1 – 55 Moderate irritant
55.1 – 80 Severe irritant
> 80.1 Very severe irritant
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
3/3
Score:
480
Reversibility:
other: not applicable
Other effects:
no data

Individual data: Opacity

Cornea-No.

Test item

Opacity blank value

Opacity post dose

Change of opacity values

Corrected opacity values

1

2

3

MV

Negative Control

3

3

3

3.00

2

1

2

1.67

-1

-2

-1

-1.33

 

4

5

6

MV

Positive Control Imidazole

6

7

5

6.00

172

158

203

177.67

166

151

198

171.67

167.33

152.33

199.33

173.00

7

8

9

MV

Test Item, Oil shale, thermal processing waste

2

4

0

2.00

456

457

456

456.33

454

453

456

454.33

455.33

454.33

457.33

455.67

Individual data: Permeability

Cornea-No.

Test Item

OD490

Corrected OD490 values

1

2

3

MV

Negative Control

0.013

0.009

0.033

0.018

 

4

5

6

MV

Positive Control Imidazole

2.097

2.113

1.306

1.839

2.079

2.095

1.288

1.820

7

8

9

MV

Test Item, Oil shale, thermal processing waste

2.132

1.839

1.030

1.667

2.114

1.821

1.012

1.649

In vitro overall irritation score

Cornea-No.

Test item

Corrected opacity value

Corrected OD490 value

In vitro Score

1

2

3

MV

Negative Control

-1

-2

-1

-1.33

0.013

0.009

0.033

0.018

 

 

 

-1.06

4

5

6

MV

Positive Control Imidazole

167.33

152.33

199.33

173.00

2.079

2.095

1.288

1.820

 

 

 

200.31

7

8

9

MV

Test Item, Oil shale, thermal processing waste

455.33

454.33

457.33

455.67

2.114

1.821

1.012

1.649

 

 

 

480.40

Interpretation of results:
other: severe irritant
Conclusions:
According to the evaluation criteria the test item Oil shale, thermal processing waste is classified as very severe irritant to eye.
Executive summary:

The eye irritancy potential of Oil shale, thermal processing waste was investigated in the bovine corneal opacity and permeability assay according to OECD guideline 437.

The test item was diluted in NaCl 0.9% to gain a 20% concentration. A mean in vitro score of 480.40 was calculated. Therefore the test item is classified as very severe irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A skin irritation study according to OECD 404 was performed with Burnt Oil Shale(BOS)-P.1082 on New Zealand White rabbits (Holcim, 2010a). Under the conditions of the studies, single dermal application of the test item BOS-P.1082 to rabbits showed neither irritant nor corrosive effects.

A skin irritation study according to OECD 404 was performed with Burnt Oil Shale(BOS)-P.1183 on New Zealand White rabbits (ICL, 2010a). Under the conditions of the studies, single dermal application of the test item BOS-P.1183 to rabbits showed neither irritant nor corrosive effects.

A skin irritation study according to OECD guideline 431 was performed on a three-dimensional human skin model EpiDerm, comprising a reconstructed epidermis with a functional stratum corneum with Burnt Oil Shale(BOS)-P.1082 (Holcim 2010b). The test item showed no corrosive effects.

According to the OECD guideline 431, the potential of the test item, Burnt Oil shale(BOS)-P.1183 to induce skin corrosion was analysed by using the three-dimensional human skin model EpiDerm, comprising a reconstructed epidermis with a functional stratum corneum (ICL, 2010b). The test item showed no corrosive effects.

 

Eye irritation:

Testing of Burnt Oil Shale(BOS)-P.1082 on isolated corneas from bovine was performed according to OECD guideline 437 in the bovine corneal opacity and permeability assay (Holcim, 2010c). A mean in vitro score of 480.40 was calculated. The negative control resulted in a mean in vitro score of -1.06 and the positive control, imidazol, revealed a mean in vitro score of 200.31. Therefore the test item is classified as very severe irritant.  

Testing of Burnt Oil Shale(BOS)-P.1183 on isolated corneas from bovine was performed according to OECD guideline 437 in the bovine corneal opacity and permeability assay (ICL, 2010c). Calculations revealed a mean in vitro irritation score of 3.58. The negative control resulted in a mean in vitro score of -1.02 and the positive control Imidazol revealed a mean in vitro score of 200.31. In the in vitro study BOS-P.1183 showed no irritating potential.

To confirm the negative results with BOS-P.1183 of the in vitro study an in vivo eye irritation study according to OECD guideline 405 with the read across substance Fluidized Bed Combustion (FBC) Fly Ash on New Zealand White rabbits was evaluated (Koryntova, 2009). No corrosive effects or any clinical signs were observed during the study schedule. FBC induced only slight irritation in rabbit eyes after a single application that was fully reversible within 12 days. As FBC has a similar composition and appearance as BOS-P.1183 this study confirms the results of the in vitro study that BOS-P.1183 is not or only slight irritating and has not to be classified for eye irritation.

 

 

 

 

 


Justification for selection of skin irritation / corrosion endpoint:
The reliable GLP compliant OECD Guideline study was chosen.

Justification for selection of eye irritation endpoint:
The reliable GLP compliant OECD Guideline study was chosen, based on a worst case scenario assumption.

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to DSD and CLP the test item Burnt Oil Shale, thermal processing residue-P.1183 has not to be classified for corrosive or irritant potential to skin or eyes.

As no information about reversibility of the observed effects in eyes is available, the test item Burnt Oil Shale, thermal processing residue-P.1082 has to be classified according to:

DSD: Xi, R41: Risk of serious damage to eyes and

CLP: Category 1, H318: Causes serious eye damage.