2-isopropyl-N-hydroxyethyl 1,3-oxazolidine;methyl carbonato-N-ethyl-2-isopropyl-1,3-oxazolidine;reaction mass of: carbonato-bis-N-ethyl-2-isopropyl-1,3-oxazolidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1998-06-11 to 1998-10-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

cited as: Directive 92/69/EEC method B.3 from 29 Dec 1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted: 24 Feb 1987

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-990-6

EC Name:

-

Molecular formula:

Not applicable as multi-const. substance. Please refer to IUCLID section 1.2 for details on constituents.

IUPAC Name:

2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethan-1-ol; 2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate; 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethan-1-ol; bis{2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl} carbonate; methyl 2-[(2R)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate; methyl 2-[(2S)-2-(propan-2-yl)-1,3-oxazolidin-3-yl]ethyl carbonate

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

other: Hsd.Brl:WH

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd. Bicester
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 232 to 268 g (males); 183 to 195 g (females)
- Fasting period before study: yes
- Housing: suspended stainless steel mesh cages (with minimum internal dimensions of 55 x 34 x 20 cm)
- Diet: ad libitum, SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd
- Water: tab water, ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 80 % RH
- Air changes: 10 air changes per hour
- Photoperiod: 12 hours light, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 5 cm
- % coverage: 10 % of the total body surface
- Type of wrap if used: elasticated, open-weave, adhesive bandage "Steroban" from Steroplast Ltd, Bredbury

REMOVAL OF TEST SUBSTANCE
The test site of each rat was lightly brushed clean of any solid residues and swabbed with moist cotton wool before the animal was returned to its cage.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 femal rats per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study, (the minimum schedule being at least once within half an hour of dosing and four times within the first four hours following administration, twice daily on Days 2. 3 and 4 and once daily from the fifth to last day of the observation period). Individual records of clinical signs and times of death were maintained for each treated rat. Rats were weighed on Day -1 and Days L, 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

A preliminary test was conducted using a group of two female rats dosed at 2000 mg/kg bw. Based on the results of this investigation the limit dose level was selected for the main study. No compound-related mortality occurred in the preliminary test. Thus, a group of five male and five female rats was subjected to single dermal application of the test article at 2000 mg/kg bw for the main test.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: There was no indication of systemic toxicity.

Gross pathology:

There were no treatment related effects to the organs.

Other findings:

Signs of toxicity (local):
One female had small foci of eshar from day 11 to 15, but the dermal change was not noted during necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Single semi-occluded topical application of Incozol LV at a dose level of 2000 mg/kg bw caused no deaths in a group of ten fasted rats. Accordingly, the acute minimum lethal dermal dose of Incozol LV to rats was found to be greater than 2000 mg/kg bw. The discriminating dose was found to be 2000 mg/kg.

Executive summary:

A study was conducted according to OECD TG 402 and Directive 92/69/EEC method B.3 to assess the acute dermal toxicity of Incozol LV in rat. A preliminary group of two female rats was subjected to a single dermal application of the undiluted liquid test article at 2000 mg/kg bw. There was no death or overt reaction to treatment. Changes apparent at the dermal test site did not exceed well defined erythema. All reactions resolved by Day 4. No macroscopic changes were seen at necropsy on Day 15. Thus, the main test was performed as limit test with a dose level of 2000 mg/kg bw. Five male and five female rats were subjected to a single semi-occluded topical application of the test item. The test article was applied to the clipped dorsum as an undiluted liquid. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy. No animal died following treatment. Staining of the snout was seen in one male and three females on Day 1 and/or Day 2. This finding is often seen during and immediately following the bandaging procedure. All rats were overtly normal by Day 3. No changes were noted at the dermal test site of the majority of rats following treatment. Multiple, small foci of eschar were seen at the dermal test site of one female from Day 11 to Day 15. This dermal change was not noted at necropsy. All rats achieved body weight gains during the first and second weeks of the study. Macroscopic examination on Day 15 revealed gaseous distension of the colon in one female and another female with a slight sore on the dermal test site.

Single semi-occluded topical application of Incozol LV at a dose level of 2000 mg/kg bw caused no deaths in a group of ten fasted rats. Accordingly, the acute minimum lethal dermal dose of Incozol LV to rats was found to be greater than 2000 mg/kg bw. The discriminating dose was found to be 2000 mg/kg bw.