Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
2017
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
No mortality occurred at the subsequent doses of 200 mg/kg, 1000 mg/kg and 2000 mg/kg.
Effect levels
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

Applicant's summary and conclusion

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.