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Administrative data

Description of key information

Acute oral toxicity OECD TG 423: 50 < LD50 < 300 mg/kg bw

Acute dermal toxicity OECD TG 402: LD50 >2000 mg/kg

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
Study period:
25 Aug 2017 - 11 Oct 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 Dec 01
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Texas Animal Specialties; Humble, TX
- Females (if applicable) nulliparous and non-pregnant: Yes
- Weight at study initiation: 190 - 238 g
- Fasting: 16 hours
- Housing: 1/cage in polycarbonate box with bedding; hutches provided as enrichment
- Diet (e.g. ad libitum): Teklad Global Diets® #2018; available ad libitum except for ~16 hours
before dosing
- Water (e.g. ad libitum): Municipal water supply analyzed by TCEQ Water Utilities Division;
available ad libitum from automatic water system
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ∙ 22 +/- 3°C
- Humidity (%): 30 - 70% target humidity
- Air changes (per hr): 10+ air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hr light/12-hr dark cycle

IN-LIFE DATES: From - To
- 2000 mg/kg bw: 01 Jul 17 - 31 Aug 17
- 300 mg/kg bw: 01 Jul 17 - 14 Sep 17
- 300 mg/kg bw:01 Jul 17 - 31 Aug 17
- 300 mg/kg bw: 01 Jul 17 - 01 Sep 17
- 50 mg/kg bw: 01 Jul 17 - 19 Sep 17
- 50 mg/kg bw: 01 Jul 17 - 21 Sep 17
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.68 mL/kg bw at the 2000 mg/kg level

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg/kg bw is the limit dose specified in regulation guideline for test items for which no information regarding toxicity is available.
Doses:
2000 mg/kg bw
300 mg/kg bw
50 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 1 female animal
300 mg/kg bw: 3 female animals
50 mg/kg bw: 6 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 times on the day of dosing, once daily for 14 days. Individual body weights were recorded
just prior to dosing and on Days 7 and 14, or at time of discovery after death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Preliminary study:
The first animal dosed at 2000 mg/kg immediately convulsed and died; therefore, per protocol amendment, the starting limit dose was changed to 300 mg/kg.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 300 mg/kg bw
Based on:
test mat.
Mortality:
The first (and only) animal dosed at 2000 mg/kg died almost immediately after being dosed. Two of the three animals dosed at 300 mg/kg died during the study. There was no mortality in either group of animals dosed at 50 mg/kg. The acute oral LDso, as indicated by the data, was determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw.
Clinical signs:
Clinical signs in survivors included hunched posture and piloerection, on the day of dosing only. One animal that died during test exhibited activity decrease and
piloerection.
Body weight:
Animals surviving to termination exhibited weekly weight gain, except for one that failed to gain, and two that lost weight between Days 7 and 14.
Gross pathology:
Abnormal necropsy findings in one animal dying during test pertained to eye closure/discharge. Gross necropsy on animals surviving to study termination revealed no observable abn01malities.
Interpretation of results:
other: Acute toxic (Category 3)
Remarks:
in accordance with Annex I of 1272/2008/EC (CLP)
Conclusions:
The acute oral LD50 for 3-Methyl Sulfolane is determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw in female albino rats; the test substance therefore needs to be classified as Category 3 acute toxicant according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).
Executive summary:

3 Methyl Sulfolane was evaluated for its acute oral toxicity potential in female albino Sprague-Dawley rats when administered as a gavage dose in a OECD 423 method, performed under GLP. The first animal dosed at 2000 mg/kg immediately convulsed and died; therefore, per protocol amendment, the starting limit dose was changed to 300 mg/kg. Two of three animals dosed at 300 mg/kg died, so no further animals were dosed at that level. No mortality occurred in the six animals thereafter dosed at 50 mg/kg. The study was terminated following stopping rules of this procedure. Clinical signs in survivors included hunched posture and piloerection, on the day of dosing only; one animal that died exhibited activity decrease and piloerection. Animals surviving to termination exhibited weekly weight gain, except for three that lost or failed to gain weight between Days 7 and 14. Abnormal necropsy findings occurred only in one animal dying during test, and pertained to eye closure/discharge. The acute oral LD50 was determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
50 mg/kg bw
Quality of whole database:
Guideline study performed in accordance with GLP.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:

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
Study period:
05 Feb 2018 - 15 Apr 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
2017
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9-12 weeks old
- Weight at study initiation: 181 to 229 g.
- Housing:
On arrival: animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.)
Following assignment to the study: animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Start dosing phase:19 Feb 2018, To: 03 April 2018
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Elix
Details on dermal exposure:
TEST SITE
- Area of exposure: 18 cm².
- % coverage: 10
- Type of wrap if used: surgical gauze patch (Surgy 1D), covered with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): unitl all residual item was removed
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight
- Concentration (if solution): 0.2 to 200 mg/mL in water
- Constant volume or concentration used: yes

VEHICLE water
- Concentration (if solution): pure
Duration of exposure:
24 hours
Doses:
200 mg/kg, 1000 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
Preliminary study:
2000 mg/kg: 1 animal
1000 mg/kg: 1 animal
200 mg/kg: 1 animal

Main study
2000 mg/kg: 2 animals
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Weighing: day 1 (predose), 8 and 15. Terminal body weights were collected from animals found dead or euthanized moribund after Day 1.
Observations: on the day of dosing (at least three times) and once daily thereafter.
Skin irritation: approximately 24, 48 and 72 hours after the removal of the dressing and test item.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal irritation
Preliminary study:
No mortality occurred at the subsequent doses of 200 mg/kg, 1000 mg/kg and 2000 mg/kg.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
One animal was found dead on Day 2
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the available information, 3-Methyl Sulfolane does not need to be classified for acute dermal toxicity according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).
According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 3-Methyl Sulfolane should be classified as: may be harmful in contact with skin (Category 5) for acute toxicity by the dermal route.
Executive summary:

3-Methyl Sulfolane was evaluated for its acute dermal toxicity potential in female rats in a OECD 402 method, performed under GLP. Initially, 3-Methyl Sulfolane was administered to single female Wistar rats by a single dermal application at 200, 1000 and 2000 mg/kg body weight for 24 hours in a range finder study. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). In the range finder, no mortality occurred and no signs of significant toxicity were observed. Based on the results, the main study was performed by dosing two females at 2000 mg/kg bw. One dosed animal was found dead on Day 2. No further mortality occurred. No irritation was noted for any of the animals at any time point. Hunched posture, piloerection, chromodacryorrhoea (snout or nose) and ptosis were noted on Days 1 and/or 2. The body weight gain shown by the surviving animals during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of 3-Methyl Sulfolane in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results:  According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 3-Methyl Sulfolane should be classified as: may be harmful in contact with skin (Category 5) for acute toxicity by the dermal route. According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures, 3-Methyl Sulfolane does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity oral

3 Methyl Sulfolane was evaluated for its acute oral toxicity potential in female albino Sprague-Dawley rats when administered as a gavage dose in a OECD 423 method, performed under GLP. The first animal dosed at 2000 mg/kg immediately convulsed and died; therefore, per protocol amendment, the starting limit dose was changed to 300 mg/kg. Two of three animals dosed at 300 mg/kg died, so no further animals were dosed at that level. No mortality occurred in the six animals thereafter dosed at 50 mg/kg. The study was terminated following stopping rules of this procedure. Clinical signs in survivors included hunched posture and piloerection, on the day of dosing only; one animal that died exhibited activity decrease and piloerection. Animals surviving to termination exhibited weekly weight gain, except for three that lost or failed to gain weight between Days 7 and 14. Abnormal necropsy findings occurred only in one animal dying during test, and pertained to eye closure/discharge. The acute oral LD50 was determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw

Acute toxicity dermal

3-Methyl Sulfolane was evaluated for its acute dermal toxicity potential in female rats in a OECD 402 method, performed under GLP.Initially, 3-Methyl Sulfolane was administered to single female Wistar rats by a single dermal application at 200, 1000 and 2000 mg/kg body weight for 24 hours in a range finder study. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). In the range finder, no mortality occurred and no signs of significant toxicity were observed. Based on the results, the main study was performed by dosing two females at 2000 mg/kg bw. One dosed animal was found dead on Day 2. No further mortality occurred. No irritation was noted for any of the animals at any time point. Hunched posture, piloerection, chromodacryorrhoea (snout or nose) and ptosis were noted on Days 1 and/or 2. The body weight gain shown by the surviving animals during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of 3-Methyl Sulfolane in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results:  According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 3-Methyl Sulfolane should be classified as: may be harmful in contact with skin (Category 5) for acute toxicity by the dermal route. According to the Regulation (EC) No 1272/2008, 3-Methyl Sulfolane does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Justification for classification or non-classification

Based on the available data, the substance needs to be classified for acute oral toxicity (Acute Tox. 3, H301) in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).

Based on the available data, the substance does not need to be classified for acute dermal toxicity in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments). According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 3-Methyl Sulfolane should be classified as: may be harmful in contact with skin (Category 5) for acute toxicity by the dermal route.