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Description of key information

Available non-human data for CAS 68516-20-1, a low benzene naphtha stream, and data on the specific component toluene, indicate that acute toxicity is expected to be low. Low benzene naphtha streams do not pose an acute hazard following ingestion (oral LD50 > 2000 mg/kg bw) or skin contact (dermal LD50 > 2000 mg/kg).  The acute inhalation 4 hour LC50 is greater than saturated vapour pressure for the stream considered and > 20 mg/L for toluene.  
However following acute inhalation exposures to toluene in humans a number of subjective sensations such as headache, dizziness, feeling of intoxication, irritation and sleepiness and decreases in acute neurobehavioural performance are seen. The NOAEC for acute neurobehavioural effects in humans is 50 ppm (188 mg/m3) and labelling will be required as low benzene naphtha streams contain up to 50% toluene.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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other: GLP compliant, guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska, USA.
- Age at study initiation: Young adults (< 12 weeks)
- Weight at study initiation: 190-350 g (pre-fast)
- Fasting period before study: overnight
- Housing: Individually in stainless steel, wire mesh bottom cages
- Diet: Agway Rodent Feed ad libitum (except during overnight pre-dose fast)
- Water: Fresh potable water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64-79°F
- Humidity: 40-70%
- Air changes: At least 10/hour
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 23 February 1990 To: 9 March 1990
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUME: 5 mL/kg. Individual dose volumes were adjusted based on the density (0.9145 g/mL) and the animals bodyweight.
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations hourly for initial 4 hours after dosing, twice daily thereafter. Bodyweights recorded pre-fast, pre-dose, week 1 and at termination.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: 1/10 mortalities and no significant macroscopic findings at only dose tested
Mortality:
0/5 males, 1/5 females (day 3).
Clinical signs:
All of the animals on study exhibited one or more of following: oral / nasal / ocular discharge, tremors, ataxia, abnormal stools, lethargy, moribund, stained coat, alopecia, hunched posture.
Body weight:
No effects.
Gross pathology:
One animal had alopecia in abdominal area, one had staining in the nasal and perineal regions.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 for E000144700 is greater than 5000 mg/kg.
Executive summary:

The acute oral toxicity of E000144700 (CAS 68516-20-1) was determined in a group of 5 male and 5 female rats administered a single dose of undiluted test substance at a dose of 5000 mg/kg. One of the animals died and adverse clinical signs including oral / nasal / ocular discharge, tremors, ataxia, abnormal stools, lethargy, moribund, stained coat, alopecia, hunched posture were observed.

The acute oral LD50 is greater than 5000 mg/kg and no classification is warranted under Dir 67/548/EEC or under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Adequate information is available on the component substances to characterise the short-term hazards of these streams after ingestion.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP near guideline study available as unpublished report (in German) but otherwise fully adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal: 7, 31.6, 52.2, 78.3, 104.4 mg/L
Analysed: 6.08, 20.00, 23.98, 38.87, 61.80 mg/L
No. of animals per sex per dose:
10
Control animals:
no
Statistics:
Probit analysis based on Finney (1971)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
28.1 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: 5/20 mortalities at 23.98 and 18/20 mortalities at 38.87 mg/L
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
25.7 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: 3/10 mortalities at 23.98 and 10/10 at 38.87 mg/L
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
30 mg/L air (analytical)
95% CL:
25.5 - 36.8
Exp. duration:
4 h
Remarks on result:
other: 2/10 mortalities at 23.98 and 8/10 mortalities at 38.87 mg/L
Mortality:
Mortality at 6.08, 20.00, 23.98, 38.87, 61.80 mg/L
Males: 0/10, 1/10, 3/10, 10/10, 10/10
Females: 0/10, 1/10, 2/10, 8/10, 10/10
Clinical signs:
other:
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Acute inhalation LC50 > 20 mg/L
Executive summary:

Acute inhalation toxicity of toluene was investigated in 5 groups of 10 male and female rats exposed for 4 hours at concentrations of 6.08, 20.00, 23.98, 38.87 or 61.80 mg/L.

Adverse clinical signs and mortality were seen at concentrations of 20 mg/L and above. All surviving animals were normal by day 3. The LC50 exceeded 20 mg/L (25.7 mg/L in males, 30 mg/L in females).

Toluene does not warrant classification under Dir 67/548/EEC or GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
20 000 mg/m³
Quality of whole database:
Adequate information is available on the component substances to characterise the short-term hazards of these streams after inhalation.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 798.1100 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive dressing used
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research, Wayne, New Jersey, USA
- Age at study initiation: Young adult
- Weight at study initiation: Approximately 2-3 kg.
- Housing: Individually in stainless steel, wire mesh bottom cages
- Diet: Agway rabbit food ad libitum
- Water: Fresh potable water ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 61-70°F
- Humidity: 40-60%
- Air changes: At least 10/hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 6 March 1990 To: 20 March 1990
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal (size of application area not reported).
- Type of wrap if used: Occlusive (no further details reported).

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg.
- Constant volume or concentration used: yes (Individual dose volumes were adjusted based on the density (0.9145 g/mL) and the animals bodyweight).
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations hourly for initial 4 hours after dosing, twice daily thereafter. Bodyweights recorded pre-fast, pre-dose, week 1 and at termination.
- Necropsy of survivors performed: yes.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: limit test, no mortalities
Mortality:
No mortalities.
Clinical signs:
All animals on study exhibited one or more of following: oedema, erythema, eschar and dried skin at test site, abnormal stools.
Body weight:
No effects.
Gross pathology:
All animals exhibited one or more of following: oedema, erythema, eschar and dried skin at test site.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for E000144700 is greater than 2000 mg/kg.
Executive summary:

The acute dermal toxicity of E000144700 (CAS 68516-20-1) was assessed in a group of 5 male and 5 female albino rabbits. The test substance was applied at 2000 mg/kg under an occlusive dressing for 24 hours. None of the animals died and there were no significant signs of systemic toxicity.

The acute dermal LD50 for E000144700 (CAS 68516-20-1) is greater than 2000 mg/kg and no classification is warranted under Dir 67/548/EEC or under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Adequate information is available on the component substances to characterise the short-term hazards of these streams after skin contact.

Additional information

There is acute toxicity data on CAS 68516-20-1, a low benzene naphtha stream, and also data for the major component toluene.

 

Non-human information

 

Acute toxicity: oral

The acute oral toxicity of low benzene naphtha streams is low. An LD50 value greater than 2000 mg/kg bw was obtained for CAS 68516-20-1. There was no significant clinical signs or pathology findings in this study. 

Acute toxicity: dermal

The dermal acute toxicity was tested for the low benzene naphtha stream CAS 68516-20-1 and the LD50 value was greater than 2000 mg/kg bw. The test substance was in contact with the skin for approximately 24 hours and an occlusive dressing was used. 

 

Acute toxicity inhalation

The 4 hour LC50 value of the low benzene naphtha stream CAS 68516-20-1 was greater than the saturated vapour pressure (5.81 mg/L air). The LC50 of toluene was calculated to be > 20 mg/L EU RAR (2003), but there was unsteady gait and other indications of neurobehavioural activity at concentrations < 20 mg/L.

 

Human information

 

There are no specific studies on the oral, inhalation or dermal toxicity in humans for streams in this category.

Data from human exposures provides information on acute toxicity for toluene:

Toluene (Classification: Category 1, H304, Cat 3 H336): The acute effects of toluene inhalation exposure include headache, dizziness, feeling of intoxication, irritation and sleepiness and decreases in acute neurobehavioural performance at concentrations ≥ 75 ppm (EU RAR, 2003). A NOAEC of 50 ppm (188 mg/m3) can be determined for acute neurobehavioural effects in humans (Muttray et al, 2005).

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

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.

Aspiration is a known hazard of hydrocarbons and is based on the physical characteristics of the low benzene naphtha streams. Kinematic viscosity values obtained range from 0.38 to 0.83 mm2/s at 40oC. Classification is warranted as these values are below the relevant cut off value of 20.5 mm2/s (hydrocarbons).

Justification for selection of acute toxicity – oral endpoint Acute oral toxicity data for representative streams indicates an LD50 of 5000 mg/kg bw or greater. 

Justification for selection of acute toxicity – inhalation endpoint Acute inhalation toxicity data for representative streams indicates an LC50 greater than saturated vapour pressure. The LC50 for the key marker substance toluene exceeds 20 mg/l (although CNS depression and neurobehavioural effects may occur at lower concentrations). 

Justification for selection of acute toxicity – dermal endpoint Acute dermal toxicity data for representative streams indicates an LD50 of 2000 mg/kg bw or greater. 

Justification for classification or non-classification

There are sufficient data on component substances to indicate that low benzene naphtha streams are of low acute toxicity by the oral, dermal and inhalation routes and do not warrant classification for these end-points under CLP.

The low kinematic viscosity of low benzene naphtha streams warrants labelling as follows: "Aspiration toxicity Category 1, H304".

Data from experimental exposure of human volunteers with toluene show that dizziness and sleepiness are experienced at air levels < 20 mg/L. Therefore, low benzene naphtha streams that contain ≥20 % toluene will justify classification Category 3 H336 under GHS/CLP.