Registration Dossier

Administrative data

Description of key information

In studies in rabbits benzene is irritating to the skin and eye but is not considered to be corrosive. In humans high concentrations of benzene vapours are irritating to the mucous membranes of the eyes, nose, and respiratory tract. Liquid benzene on direct contact with the skin may cause erythema and defatting.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline compliant study, GLP status unknown, limitations in reporting but otherwise acceptable.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Type of coverage:
other: under exposure chamber
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Neat, 0.5 mL, to an area of 6cm2
Duration of treatment / exposure:
4 hours
Observation period:
144 h (i.e. 6 days) after end of application
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24/48/72 h
Score:
> 2
Reversibility:
no data
Remarks on result:
other: erythema score 3.00 at 144 h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24/48/72
Score:
0
Reversibility:
fully reversible
Remarks on result:
other: oedema only seen at 1 h

Mean scores (Draize et al 1944):

Time after end of application

1 h

24 h

48 h

72 h

144 h

Mean score for erythema

1.00

2.00

2.20

2.40

3.00

Mean score for edema

2.20

0.00

0.00

0.00

0.00

 

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Benzene is considered to be irritating to rabbit skin (mean over 24/48/72 h for erythema >2)
Executive summary:

The irritation potential of benzene was assessed on the skins of six shaved rabbits exposed to neat benzene for 4 hours, using an exposure chamber of 6 cm2. One hour after exposure oedema grade 2 and erythema grade 1 were documented. No oedema, but mean scores of 2.0/2.2/2.4 for erythema were recorded at 24, 48, and 72 hours after the end of exposure. Erythema increased to a mean of grade 3 at 6 days.

It is concluded that benzene is irritating to rabbit skin and should be classified as Xi, R38. Under CLP it is proposed that the appropriate classification is Category 2, H315.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, animal experimental study, predates implementation of GLP and guideline studies but contributing to a weight of evidence.
Guideline:
other: Pre-guideline method
Principles of method if other than guideline:
Pre-guideline method: test substance instilled into right eye and irritation and corneal injury assessed.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: Albino rabbits
- Source: Heterogeneous stock raised at Dow Chemical Company, Biochemical Research Dept.
- Diet: Commercial diet, supplemented with alfalfa hay

ENVIRONMENTAL CONDITIONS: No details reported
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
Two drops of undiluted material (no further detail reported)
Duration of treatment / exposure:
Single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
Not reported
Irritation parameter:
conjunctivae score
Basis:
other: narrative score, no individual data
Time point:
other: all
Reversibility:
not specified
Remarks on result:
other: inflammation and slight swelling of the eyelids
Irritation parameter:
cornea opacity score
Basis:
other: narrative score, no individual data
Time point:
other: all
Reversibility:
fully reversible
Remarks on result:
other: very slight, transient corneal injury comprising questionable or just perceptible superficial necrosis involving less than 50% of the cornea
Irritant / corrosive response data:
No individual or mean data provided. Overall narrative description only.

Moderate conjunctival irritation (i.e. inflammation and slight swelling of the eyelids) and very slight transient corneal injury (i.e. questionable or just perceptible superficial necrosis in very small areas of the cornea) were recorded.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Benzene is considered to be mildly irritating to rabbit eyes.
Executive summary:

Instillation of benzene into the rabbit eye caused moderate conjunctival irritation and very slight, transient corneal injury. It is concluded that benzene is irritating to rabbit eyes and should be classified as Xi, R36. Under CLP it is proposed that the appropriate classification is Category 2, H319.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Non-human information

Skin irritation

The irritation potential of benzene was assessed on the skins of six shaved rabbits exposed to neat benzene for 4 hours, using an exposure chamber of 6 cm2 (Jacobs. 1991). One hour after exposure oedema grade 2 and erythema grade 1 were documented. No oedema, but mean scores of 2.0/2.2/2.4 for erythema were recorded at 24, 48, and 72 hours after the end of exposure. Erythema increased to a mean of grade 3 at 6 days. A second study (Wolf et al, 1956) examined skin irritation potential of benzene following repeated applications. Undiluted benzene was applied 10 -20 times over 2-4 weeks to the ear and shaved abdomen of white rabbits (abdomen bandaged). Perceptible to definite erythema, oedema and superficial necrosis were documented. These effects resulted in a "chapped" appearance and exfoliation of large patches of skin. Although the design and reporting are not compliant with regulatory guidelines the results are consistent with benzene being irritating to rabbit skin.

Eye irritation

The key study is considered to be Wolf et al (1956). Instillation of benzene into the rabbit eye caused moderate conjunctival irritation and very slight, transient corneal injury.

Human information

Skin irritation

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.

Eye irritation

High concentrations of benzene vapours are irritating to the mucous membranes of the eyes, nose, and respiratory tract (EU RAR, 2008).


Justification for selection of skin irritation / corrosion endpoint:
Liquid benzene is irritating to rabbit skin, and removes fat from the tissue which may result in the development of a dry, scaly dermatitis if exposure is repeated or prolonged.

Justification for selection of eye irritation endpoint:
Liquid benzene is irritating to rabbit eye, causing moderate conjunctival irritation and very slight, transient corneal injury.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

It is concluded that benzene is irritating to rabbit skin and should be classified as Xi, R38. Under CLP it is proposed that the appropriate classification is Category 2, H315.

Benzene is irritating to rabbit eyes and should be classified as Xi, R36. Under CLP it is proposed that the appropriate classification is Category 2, H319.