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Administrative data

Description of key information

Acute oral LD50 (rat): 2068 mg/kg

Acute dermal LD50 (rat): >2000mg/kg

Acute inhalation LC50 (rat, 4-hr): >12,000 mg/m3

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
No further information available.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 weeks of age
- Weight at study initiation: 122-138 g for males; 107-120 g for females
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No information is available.
Doses:
892, 1204, 1626, 2195, 2963, and 4000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was weighed immediately prior to treatment, the day and thereafter 1, 3, 7 and 14 days after treatment. The rats were observed periodically during the two-week post-treatment observation period.
- Necropsy of survivors performed: yes
Statistics:
LD50 was calculated by Van der Waerden method
Preliminary study:
No information is available.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 006 mg/kg bw
Remarks on result:
other: 1783 – 2256
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 130 mg/kg bw
Remarks on result:
other: 1844 - 2460
Mortality:
Males: 4/5, 5/5, and 5/5 at 2195, 2963, and 4000 mg/kg, respectively. Females: 3/5, 5/5, and 5/5 at 2195, 2963 and 4000 mg/kg, respectively.
Clinical signs:
Males at >/=1626 mg/kg: convulsions, decreased locomotor activity, ptosis, salivation, piloerection, chromodacryorrhea and perineal region soiling with urine. [CONFIRM THAT THESE EFFECTS REFER TO MALES]

Females at >/= 1626 mg/kg: decreased locomotor activity

Females at >/= 2195 mg/kg: convulsions, ptosis, salivation, piloerection, chromodacryorrhea, perineal soiling with urine. [CONFIRM THAT THESE EFFECTS REFER TO FEMALES]

Body weight:
Reduced body weights in all treated dose groups compared to controls on the day after dosing.
Gross pathology:
Dead animals showed hemorrhagic black spots in their glandular stomach mucosa at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 in male and female rats were 2006 and 2130 mg/kg, respectively.
Executive summary:

A single oral dose of sulfolane was administered to rats by gavage at doses of 0, 892, 1204, 1626, 2195, 2963, and 4000 mg/kg. The acute oral LD50 in male and female rats were established at 2006 and 2130 mg/kg, respectively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 068 mg/kg bw

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Guideline:
other: Other: Andersen et al. (1977)
Principles of method if other than guideline:
No further information available.
GLP compliance:
not specified
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
- Weight at study initiation: 260 – 480 g
- Diet: Commercial prepared dry chow ad libitum except during exposure
- Water: ad libitum except during exposure.
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole-body inhalation system: cylindrical glass battery jar supported in a Plexiglas frame.
- Exposure chamber volume: 30 Liter
- Method of holding animals in test chamber: The animals were kept singly in compartmentalized wire cages
- Aerosols were generated using a glass nebulizer and final chamber concentrations were varied by altering the drop rate of test material into the nebulizer. Particle size distribution analysis of the aerosol was between 1 and 4 um in mean particle size diameter. Exposures were made at various concentrations, all of which were below the aerosol concentration which caused wetting of the animals and chamber surfaces (Approximately 12,000 mg/m3).

TEST ATMOSPHERE
Atmospheric sulfolane concentrations were determined by drawing known volumes of chamber air first through an impinger and then through a bubbler containing distilled water. The aerosolized sulfolane trapped by the impinger was dissolved in distilled water. Sulfolane in these aqueous solutions was determined by gas-liquid chromatography with flame ionization detection. Samples were taken every 6 hours during the exposures.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Approximately 12,000 mg/m3
No. of animals per sex per dose:
Not reported.
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 2 weeks
Statistics:
Not necessary.
Preliminary study:
No information is available.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
12 000 other: mg/m³ aerosol/vapor
Exp. duration:
4 h
Remarks on result:
other: no mortality
Mortality:
No mortality.
Clinical signs:
Not reported.
Body weight:
Not reported.
Gross pathology:
Not reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of sulfolane aerosol/vapor was >12,000 mg/m3 in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
12 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
Directive 84/449/EEC. No further information available.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD.BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K., Ltd.
- Age at study initiation: At least 7-8 weeks
- Weight at study initiation: mean Not reported
- Fasting period before study: Overnight
- Housing: 1-3 rats in stainless steel wire-mesh cages
- Diet: LAD 1, Special Diets Services, Ltd. ad libitum, except for pre-dose fast
- Water: Tap water ad libitum
- Acclimation period: at least seven days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 – 23°C
- Humidity: 30 – 70%
- Air changes (per hr): Not reported
- Photoperiod: 12 hrs dark / 12hrs light


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test Site
- Type of wrap if used: a gauze dressing (approx. 6 x 8 cm) covered with waterproof adhesive tape.

Removal of Test Substance
- Washing (if done): with warm dilute detergent solution
- Time after start of exposure: 24 hours

Test Material
- Amount(s) applied (volume or weight with unit): 1.59 mL/kg
- Constant volume or concentration used: yes
Duration of exposure:
24 hours.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations made at least six times on the day of dosing and twice daily thereafter for the remainder of the study. Body weights were measured prior to dosing, and thereafter on Day 1, 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
Not needed
Preliminary study:
No information is available.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
The majority of rats showed staining (yellow) of the anogenital fur and one rat showed an unkempt appearance on Day 2 only. Erythema or discoloration (yellow) of the sites of application of the test material were common after removal of the dressings on Day 2. All dermal changes resolved by Day 4.
Body weight:
All rats had gained weight relative to their Day 1 body weights by the end of the first and second weeks of the 14-day observation period.

Gross pathology:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal rat LD50 of sulfolane was greater than 2000 mg/kg. No deaths were observed.

Executive summary:

Undiluted sulfolane at a dose of 2000 mg/kg was applied to the skin of male and female Sprague-Dawley rats for 24 hours by an occlusive patch. There were no deaths. The acute dermal LD50 of sulfolane in rats is greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute Oral

The Japan MHW (1996) reported an OECD TG 401 study with sulfolane. The oral LD50 in male and female rats were 2006 and 2130 mg/kg, respectively. In male rats, the mortality rate was 0%, 0%, 0%, 80%, 100% and 100% at 892, 1204, 1626, 2195, 2963 and 4000 mg/kg. At >1626 mg/kg, there were convulsions, decreased locomotor activity, ptosis, salivation, piloerection, chromodacryorrhea and perineal region soiling with urine. In females, the mortality rate was 0%, 0%, 0%, 60%, 100% and 100% at 892, 1204, 1626, 2195, 2963 and 4000 mg/kg.  At >1626 mg/kg, there was decreased locomotor activity. A t>2195 mg/kg, there was convulsions, ptosis, salivation, piloerection, chromodacryorrhea, perineal soiling with urine.

Hazleton (1983a) reported oral rat LD50 values of 2739, 2108 and 2363 mg/kg in males, females and both sexes combined, respectively.

Acute Inhalation

Andersen et al. (1977) exposed male and female Sprague-Dawley rats for four hours to approximately 12,000 mg/m3 of an aerosol/vapor mixture of sulfolane. There were no deaths. The 4-hr rat LC50 is >12,000 mg/m3.

Acute Dermal

SRC (1993) reported the acute dermal rat LD50 of sulfolane to be >2000 mg/kg. Undiluted sulfolane at a dose of 2000 mg/kg was applied to the skin of male and female Sprague-Dawley rats for 24 hours by an occlusive patch. There were no deaths. The majority of rats showed staining (yellow) of the anogenital fur and one rat showed an unkempt appearance on Day 2 only. Erythema or discoloration (yellow) of the sites of application of the test material were common after removal of the dressings on Day 2. All dermal changes resolved by Day 4.

Justification for classification or non-classification

Acute Oral

Classification proposal regarding acute oral toxicity: GHS/CLP: None (Category 5).

Acute Inhalation

Classification proposal regarding acute inhalation toxicity: GHS/CLP: None.  

Acute Dermal

Classification proposal regarding acute dermal toxicity: GHS/CLP: None.