Registration Dossier

Administrative data

Description of key information

Data available data for one stream within this category (CAS 68516-20-1) and on specific constituents that are present in some streams (benzene, DCPD, toluene, and xylene) provide some evidence of skin and eye irritation with controlled exposures to liquid test substances although the severity varies widely. Xylenes are also considered to be respiratory irritants. It is assumed that the total concentration of irritating components exceeds 20% and that High Benzene Naphtha streams should be considered to be skin and eye irritants and to be classified appropriately. The need for classification with respect to respiratory tract irritation is dependent upon available data for the specific stream or the concentration of xylenes in the stream.

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
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other: GLP compliant, guideline study, available as unpublished report, minor restrictions in reporting but otherwise adequate for assessment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: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 5 February 1990 To: 8 February 1990
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other:
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 h
Observation period:
72 h
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:
other: 24, 48, 72 hours
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:
other: 24, 48, 72 hours
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:
irritating
Remarks:
Migrated information 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
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key 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.
Qualifier:
no guideline available
Principles of method if other than guideline:
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 Category 2, H319 under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Non human data

Skin irritation

The stream E000144700 (CAS 68516-20-1) has been tested in animal studies and shown to be irritating but not corrosive to rabbit skin (UBTL, 1990d). Data on the specific constituents benzene (Jacobs et al, 1991), toluene (Exxon, 1988), and xylene (Chatterjee et al, 2005; Chevron Chemical Company, 1973; Hines et al, 1970), and DCPD (Safepharm 1989) indicate some irritation following dermal contact with effects sufficiently severe to warrant classification.

Eye irritation

Data on E000144700 (CAS 68516-20-1) and on specific component toluene and DCPD, 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 (Wolf et al, 1956; Carpenter and Smyth, 1946) and xylene (Hine et al, 1970; HLA, 1983c, d) the effects are sufficient to warrant classification.

Respiratory irritation

There are no specific data on any of the streams but the constituent xylene is classified as “irritating to respiratory system” (De Ceaurriz et al, 1981; HLA, 1983a, b).

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, toluene and xylene:

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, 2008b).

Toluene (Classification: Category 2 H315): No data on skin irritation have been found. 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. 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.

Xylene (Classification: Category 2 H315; Self classification: Category 2 H319, Category 3 H335, Category 2 H315): There is little human information available but the ATSDR (2007c) reports that dermal exposure of humans to xylene causes skin irritation, dryness and scaling of the skin, and vasodilation. Mild irritation of the eye and upper respiratory tract was reported in volunteer studies where individuals were exposed to 442 mg/m3(SCOEL, 1992) for 15-30 minutes (Carpenter, 1975; Hastings, 1984). No symptoms of nose or throat irritation have been reported in volunteers exposed to mixed xylenes up to 400 ppm (UK, 2001).

References

ATSDR (2007c). Toxicological profile for xylene. US Dept Health and Human Services.

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

EU (2008b). 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.

SCOEL (1992). Recommendation from the scientific expert group on occupational exposure limits for xylenes.

UK HSC (2001). UK HSC Consultation Document on EC Directive 2000/39/EC establishing a first list of indicative occupational exposure limit values at EC level in implementation of council directive 98/24/EC on the protection of the health and safety of workers from the risks related to chemical agents at work. UK Health and Safety Commission. Available from www.hse.gov.uk/condocs.

 

Justification for selection of skin irritation / corrosion endpoint:

Information available for representative streamand the marker constituents indicates a potential to cause skin irritation.

 

Justification for selection of eye irritation endpoint:

Information available for representative and the marker constituents present in these streams indicates a potential to cause eye irritation.

 

Effects on skin irritation/corrosion: irritating

 

Effects on eye irritation: irritating

Justification for classification or non-classification

There are sufficient data on the stream CAS 68516-20-1 and on component substances benzene, toluene and xylene to indicate that they produce evidence of skin and eye irritation in animals although the response varies and is not always of a severity to warrant classification for eye irritation. However, based on likely concentrations of components and in order to be protective it is recommended that all High Benzene Naphtha streams should be considered to be skin and eye irritants. Classification and labelling will be required as follows: “Causes skin irritation” Category 2 H315, “Causes serious eye damage” Category 2 H319 according to Reg (EC) 1272/2008.

High Benzene Naphtha streams containing ≥10% xylene and/or DCPD should be classified “May cause respiratory irritation” Category 3 H335 under Reg (EC) 1272/2008.