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Description of key information

It can be concluded that low benzene naphtha streams are irritating to rabbit skin but not irritating to the rabbit eye. Data for the specific component toluene is consistent with this classification. In addition it is noted that the exposure to this C7-C12 petroleum-derived aromatic stream was more severe than required by the test guidelines (24 hr contact time under occluded conditions), and therefore classification is based on data obtained for the specific low benzene naphtha stream in this category.

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other: GLP compliant, guideline study, available as unpublished report, minor restrictions in reporting but otherwise adequate for assessment
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
occlusive dressing used
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sterling Rabbitry, Wellsville, Utah, USA.
- Age at study initiation: Young adult
- Weight at study initiation: 2.0-4.0 kg
- Housing: Individually in stainless steel, wire mesh bottom cages.
- Diet: Fresh certified Agway rabbit feed ad libitum
- Water: Fresh potable water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 61-71°F
- Humidity: 40-60%
- Air changes: At least 10 per hr
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 5 February 1990 To: 8 February 1990
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorsal area (approximately 1 square inch).
- Type of wrap if used: gauze patch taped with hypoallergenic tape and wrapped with an impervious, non-reactive rubberised material and taped in place.
SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.8
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: scores at all time points
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: scores at all time points
Interpretation of results:
other: Irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
E000144700 is irritating but not corrosive to the skin.
Executive summary:

The primary dermal irritation of E000144700 (CAS 68516-20-1) was investigated in a group of 6 albino rabbits. 0.5 mL of neat test substance was applied to approximately 1 square inch of shaved dorsal skin and retained in contact for 4 hours under an occlusive dressing. Erythema and oedema was seen in all six animals from 1 hour until 72 hours after removal of the dressing. Mean erythema and oedema scores over 24, 48 and 72 hours were greater than 2.

E000144700 (CAS 68516-20-1) is irritating to rabbit skin and warrants classification Category 2, H315 under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
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, minor restrictions reporting but otherwise adequate for assessment
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Sterling Rabbitry, Wellsville, Utah, USA.
- Age at study initiation: Young adult
- Weight at study initiation: 2.0-4.0 kg
- Housing: Individually in stainless steel, wire mesh bottom cages.
- Diet: Fresh certified Agway rabbit feed ad libitum
- Water: Fresh potable water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 61-71°F
- Humidity: 40-60%
- Air changes: At least 10 per hr
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 20 February 1990 To: 23 February 1990
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:
6
Details on study design:
SCORING SYSTEM: Based on the Draize scale
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: effects in all 6 rabbits 1, 24 and 48 hours, in 5 rabbits at 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: effects in all 6 rabbits 1, 24 and 48 hours, in 5 rabbits at 72 hours

After 1, 24 and 48 hours, conjunctival redness and chemosis were present in all six rabbits, after 72 hours these conditions still persisted in five animals. Conjunctival discharge was present in one rabbit only at the 1 hour reading. There was no corneal or iridial involvement in any animal.

Table 1: Eye irritation scores

Time

Cornea

Iris

Conjunctiva

Redness

Chemosis

Animal number

91

95

101

104

105

106

91

95

101

104

105

106

91

95

101

104

105

106

91

95

101

104

105

106

after 1 hour

0

0

0

0

0

0

0

0

0

0

0

0

3

2

2

3

3

2

3

1

2

1

1

2

after 24 hours

0

0

0

0

0

0

0

0

0

0

0

0

3

1

2

2

2

2

2

1

2

1

1

2

after 48 hours

0

0

0

0

0

0

0

0

0

0

0

0

2

0

1

2

2

2

2

1

1

1

1

2

after 72 hours

0

0

0

0

0

0

0

0

0

0

0

0

2

0

1

2

1

2

2

0

1

1

1

2

mean scores 24-72h

0

0

1.6

1.3

 

 

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
E000144700 is not irritating to the rabbit eye.
Executive summary:

Eye irritation potential of E000144700 (CAS 68516-20-1) was determined in a group of six 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 72 hours after application. Mean scores over 24, 48 and 72 hours were: cornea 0, iris 0, conjunctival redness 1.6, chemosis 1.3.

E000144700 (CAS 68516-20-1) was not irritating to the rabbit eye and does not warrant classification under Dir 67/548/EEC or 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 data

Skin irritation

Skin irritation studies are available for one low benzene naphtha stream. CAS 68516-20-1 was concluded to be irritating, but not corrosive, to rabbit skin. The skin irritation potential of toluene was assessed in 7 rabbits according to EU method B4 (Exxon, 1988). Toluene caused significant inflammation of the skin and was classified as irritating to skin.

Eye irritation

Eye irritation studies are available for one low benzene naphtha stream. This stream (CAS 68516-20-1) was concluded not to be irritating to the rabbit eye. Data on the specific component toluene indicates that instillation of liquid test substance into the eye may induce some evidence of eye irritation but not of a severity that warrants labelling (Exxon, 1995).

Respiratory irritation

There are no specific data on low benzene naphtha streams or on toluene relating to irritation of the respiratory system.

Human information

There is no specific human information concerning skin or eye irritation on the low benzene naphtha streams. Although no data have been found for toluene, the EU RAR (2003) 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. 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 RAR (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

Exxon (1988). Primary dermal irritation study in the rabbit. Testing laboratory: Exxon Biomedical Sciences, Toxicology Laboratory, Mettlers Road, CN 2350, East Millstone, New Jersey 08875-2350. Owner company: Exxon. Study number: 225904. Report date: 1988-07-29.

Exxon (1995). Ocular irritation study in the rabbit without eyewash with toluene (compliant with OECD test guideline 405). Testing laboratory: Exxon Biomedical Sciences Inc, Toxicology laboratory, Mettlers Road, CN 2350, East Millstone, New Jersey 08875-2350. Owner company: Exxon. Study number: 191813.

Muttray A, Spelmeyer U, Hommel G, Oesch F, Jung D, Rose D, Mayer-Popken O, Rossbach B and Letzel S (2005). Acute exposure to 50 ppm toluene does not increase sleepiness. Environ. Toxicol. Pharmacol. 19, 665-669.


Justification for selection of skin irritation / corrosion endpoint:
Skin irritation data for representative streams, together with information on the key marker substance toluene, indicate that members of this category will be irritating to skin.

Justification for selection of eye irritation endpoint:
Eye irritation data for representative streams, together with information on the key marker substance toluene, indicate that members of this category will not be irritating to the eye.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

There are sufficient data on the low benzene naphtha stream and CAS 68516-20-1 and the specific component, toluene, to indicate that low benzene naphtha streams are irritating to rabbit skin but not irritating to the eye and should be classified as Category 2 H315 according to CLP.