Registration Dossier

Administrative data

Description of key information

Available data for four streams within this category: CAS 64742-90-1, CAS 68475-80-9, CAS 85117-10-8, CAS 98072-36-7 and specific components that are present in some streams (benzene, toluene, dicyclopentadiene, ethylbenzene, styrene) provide some evidence of skin toxicity.It is assumed that the total concentration of skin irritating constituents exceeds 20% and that Fuel Oils streams should be considered to be skin irritants and need to be classified appropriately.There is some evidence of eye irritation with controlled exposures to liquid test substances although the severity varies widely. Ethylbenzene is also considered to be a respiratory irritant. Multiple category constituents are also considered to be respiratory irritants. The need for classification with respect to respiratory tract irritation is dependent upon the concentration of classified constituents in the stream. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
In Vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
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)
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: ENKI-Konijnenfarm, Someren, the Netherlands
- Age at study initiation: young adult
- Sex: male
- Weight at study initiation: 2860-3300 g
- Housing: individually in suspended, galvanized cages, fitted with a wire mesh floor and front
- Diet: standard laboratory rabbit diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 ± 3°C
- Humidity: at least 40%
- Air changes (per hr): approx. 10
- Photoperiod: natural day/night cycle

IN-LIFE DATES: From: 22 May 1989 To: 2 June 1989
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
10 days. Assessment of skin irritation made approx 1 hour after removal of dressings and after 24, 48 and 72 hours and 7 and 10 days.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: 2.5 x 2.5 cm patch (Melolin, Smith & Nephew), fixed to the application site by means of adhesive tape (Leukopor, BDF). The entire trunk of the rabbit was wrapped with a self-adhesive gauze.

REMOVAL OF TEST SUBSTANCE
- Washing: remains of the test substance, which could not be removed water, were removed using Nivea cream.

- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.8
Max. score:
4
Reversibility:
fully reversible within: 7-10 days
Remarks on result:
other: very slight to moderate to severe erythema in all 3 animals 24, 48 and 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.6
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: very slight to slight oedema in 2 animals for up to 72 hours
Irritant / corrosive response data:
At 1 hour and 24 hours well-defined or moderate erythema present in 3 rabbits and very slight or slight oedema in 2 rabbits. At 48 hours well-defined erythema with or without very slight oedema in all 3 rabbits. At 72 hours very slight erythema with or without very slight oedema present in all 3 rabbits. At 7 days skin effects had cleared completely in 1 rabbit, whereas the others had very slight erythema or slight scaliness. All signs of irritation had cleared by 10 days. No signs of corrosion in any rabbit.

Individual and mean skin irritation scores of Carbon Black-DSM Roetolie according to the Draize scheme

Time

Erythema

Oedema

Animal number

53

55

56

53

55

56

after 1 hour

3

2

2

2

1

0

after 24 hours

3

2

2

2

1

0

after 48 hours

2

2

2

0

1

0

after 72 hours

1

1

1

0

1

0

mean score 24-72 h

2.0

1.7

1.7

0.7

1.0

0

after 7 days

0

0s

1

0

0

0

after 10 days

0

0

0

0

0

0

s – slight scaliness

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Carbon Black-DSM Roetolie is slightly irritating but not corrosive to skin.
Executive summary:

The skin irritation potential of undiluted Carbon Black-DSM Roetolie (CAS 64742-90-1) was assessed under occluded conditions in 3 New Zealand white rabbits using an exposure period of 4 hours.

Erythema was seen in all 3 rabbits which persisted for up to 10 days in 1 animal. Oedema, persisting for up to 7 days, was seen in 2 rabbits. Mean scores over 24, 48 and 72 hours were 1.8 for erythema and 0.6 for oedema.

It can be concluded that Carbon Black-DSM Roetolie (CAS 64742-90-1) is not irritating to rabbit skin and no classification is warranted under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
In Vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, the Netherlands
- Age at study initiation: young adult
- Sex: male
- Weight at study initiation: 2700-2870 g
- Housing: individually in suspended, galvanized cages, fitted with a wire mesh floor and front
- Diet: standard laboratory rabbit diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 ± 3°C
- Humidity: at least 40%
- Air changes (per hr): approx. 10
- Photoperiod: natural day/night cycle

IN-LIFE DATES: From: 22 May 1989 To: 25 May 1989
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Corneal opacity on a 0-4 scale, iritis on a 0-2 scale, conjunctival redness on a 0-3 scale, conjunctival chemosis on a 0-4 scale

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no corneal effects
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Remarks on result:
other: no iridial effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: minimal redness in 3 animals 1- 24 hours and 1 animal at 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: minimal chemosis in 3 animals 1- 24 hours and 1 animal at 48 hours
Irritant / corrosive response data:
After 1 hour slight redness with or without slight swelling of the conjunctivae. At 24 hours slight redness and slight swelling of the conjunctivae. At 48 hours the eye effects had cleared completely in two of the three rabbits, whereas slight redness and slight swelling of the conjunctivae were observed in the third rabbit. All irritation had cleared by 72 hours.
Other effects:
The test substance adhered to the hair surrounding the eye in all 3 rabbits.

Eye irritation scores of Carbon Black-DSM Roetolie

Time

Cornea

Iris

Conjunctiva

 

 

 

 

Redness

Chemosis

 

Animal number

63

73

74

63

73

74

63

73

74

63

73

74

after 1 hour

0

0

0

0

0

0

1

1

1

1

0

0

after 24 hours

0

0

0

0

0

0

1

1

1

1

1

1

after 48 hours

0

0

0

0

0

0

0

0

1

0

0

1

after 72 hours

0

0

0

0

0

0

0

0

0

0

0

0

mean scores 24-72h

0

0

0

0

0

0

0.3

0.3

0.7

0.3

0.3

0.7

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Carbon Black-DSM Roetolie is not irritating to eyes.
Executive summary:

Eye irritation potential of carbon black-DSM Roetolie (CAS 64742-90-1) was determined in a group of three albino rabbits.

There was no evidence of damage to the cornea or iris throughout the study. Conjunctival redness and chemosis was seen from 1 hour to 48 hours after application. Mean scores over 24, 48 and 72 hours were: cornea 0, iris 0, conjunctival redness 0.4, chemosis 0.4.

Carbon black-DSM Roetolie (CAS 64742-90-1) was not irritating to the rabbit eye and does not warrant classification under GHS CLP.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Non-human information

Skin irritation

The category streams CAS 68475-80-9, CAS 85117-10-8, and CAS 98072-36-7 have been tested in animal studies and shown to be irritating but not corrosive to rabbit skin, whereas CAS 64742-90-1 produced only minor effects which showed full recovery and no classification is warranted. Data on the specific components benzene, toluene, ethylbenzene, styrene, anthracene and dicyclopentadiene indicate some irritation following dermal contact with effects sufficiently severe to warrant classification.

Eye irritation

Data on the category streams: CAS 64742-90-1, CAS 68475-80-9, CAS 85117-10-8, CAS 98072-36-7 and on specific constituent toluene indicate that instillation of liquid test substance into the eye may induce some evidence of eye irritation but not of a severity that warrants classification. For benzene, ethylbenzene, dicyclopentadiene, anthracene and styrene the effects are sufficient to warrant classification.

Respiratory irritation

There are no specific data on any of the streams, but ethylbenzene is considered to be irritating to the respiratory tract. For ethylbenzene RD50 values of 1432 or 4060 ppm (6215 to 17620 mg/m3) for sensory irritation were determined in different strains of mice (EU, 2008b).

Human information

There is no specific human information concerning skin or eye irritation on any of the streams or on the majority of specific components identified as present in some streams. Specific information of value to the risk assessment is available for benzene and toluene:

Benzene (Classification: Category 2 H319, Category 2 H315): Liquid benzene on direct contact with the skin may cause erythema and blistering. Skin contact with benzene removes fat from the tissue which may result in the development of a dry, scaly dermatitis if exposure is repeated or prolonged. High concentrations of benzene vapours are irritating to the mucous membranes of the eyes, nose and respiratory tract (EU, 2008a).

Toluene (Classification: Category 2 H315): No data on skin irritation have been found. The EU RAR (2003a) stated “it is well known that toluene has a degreasing effect on the skin. After repeated exposures, toxic contact dermatitis may develop. ” There are no data from direct exposure of human eyes to liquid toluene. A number of human experimental studies in volunteers have investigated reports of eye “irritation” resulting from exposures to toluene in ambient air. These studies indicate that toluene produces subjective sensations of eye irritation at concentrations ≥ 75 ppm (EU, 2003a). In a recent study, Muttray et al (2005) exposed twenty healthy men to a constant level of 50 ppm toluene. Acute symptoms related to eye irritation were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and 3 times during exposure. Values obtained during exposure were related to pre-exposure values. There was no effect of toluene exposure on "irritation to the eye", "watering eyes" or "blurred vision”. 50 ppm (188 mg/m3) toluene is a NOAEC for eye irritation in humans.

References

EU (2008a). European Union Risk Assessment Report for Benzene. EC Joint Research Centre. http: //ecb. jrc. ec. europa. eu/documents/Existing-chemicals/RISK_ASSESSMENT/REPORT/benzenereport063.pdf

EU (2003a). European Union Risk Assessment Report for Toluene. EC Joint Research centre. http://ecb.jrc.ec.europa.eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/toluenereport032.pdf


Justification for selection of skin irritation / corrosion endpoint:
Experimental data for four streams within this category, together with information on the component substances that are present, indicates a potential to cause skin irritation.

Justification for selection of eye irritation endpoint:
Experimental data for four streams within this category indicate some potential to cause eye irritation. Various component substances that are present may cause eye irritation.

Effects on skin irritation/corrosion: irritating


Effects on eye irritation/corrosion: not irritating

Justification for classification or non-classification

Data on the streams: CAS 68475-80-9), CAS 85117-10-8, CAS 98072-36-7 and on the component substances benzene, toluene, ethylbenzene, styrene, and dicyclopentadiene demonstrate that they are irritating to rabbit skin. Data on one stream CAS 64742-90-1indicate that it produces only minor evidence of skin irritation. However, based on likely concentrations of components and in order to be protective it is recommended that all Fuel Oils streams should be considered to be skin irritants. Classification and labelling will be required as follows: “Causes skin irritation” Category 2 H315, “Causes serious eye damage” according to Reg (EC) 1272/2008.

Information on tested streams: CAS 64742-90-1, CAS 68475-80-9, CAS 85117-10-8, CAS 98072-36-7 and on the component substances toluene and naphthalene indicate that they are not irritant to the eye and so these streams and streams that only contain these substances will not need to be classified for eye irritating properties. Benzene and styrene, and many other constituents are classified as irritating to the eye, therefore Fuel Oils streams containing ≥10% overall concentration of Category 2 eye irritants should be labelled “Causes serious eye irritation” Category 2 H319 under Reg (EC) 1272/2008.

Fuel Oils streams containing ≥20% of Category respiratory irritants should be classified as “May cause respiratory irritation” Category 3 H335 under Reg (EC) 1272/2008.