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

Endpoint summary

Description of key information

Oral

The discriminating dose of the oral toxicity was found to be 2000 mg/kg bw.

Dermal

The discriminating dose of the dermal toxicity was found to be 2000 mg/kg bw.

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:

from 1998-02-12 to 1998-04-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

cited as: Directive 92/69/EEC method B1 bis, from 29 Dec 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted: 17 Jul 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: five to eight weeks old
- Weight at study initiation: 145 to 159 g (males); 129 to 143 g (females)
- Fasting period before study: yes; from the evening prior to dosing until approximately three hours after dosing
- Housing: stainless steel mesh cages (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. Witham
- Water: tab water ad libitum
- Acclimation period: 9 days

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

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Desiccated corn oil

Details on oral exposure:

VEHICLE
Dose levels were expressed gravimetrically and in terms of test article received. The test article was dispersed in desiccated com oil. The formulated concentrations were calculated from the selected dose level and dose volume (10 mL/kg). All formulations were used on the day of preparation.

MAXIMUM DOSE VOLUME APPLIED:
Individual dose volumes (mL) were calculated from the fasted body weights of the rats on the morning of dosing (Day 1) and the selected dose volume (10 mL/kg). Each rat was dosed once on Day 1 by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen. Doses were administered using plastic syringes and rubber catheters.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and female rats per sex 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 were maintained for each treated rat. Rats were weighed on Day -1 (day before dosing), Day 1, Day 8 and Day 15.
- Necropsy of survivors performed: yes

Preliminary study:

The preliminary investigation was conducted using two groups of two female fasted rats dosed at 500 and 2000 mg/kg. There were no deaths among pairs of female fasted rats following a single oral administration of Ineozol LV at either 500 or 2000 mg/kg. Thus, the main test was performed with a dose level of 2000 mg/kg bw.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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 were no treatment related signs of toxicity following administration of the test substance.

Gross pathology:

Necropsy revealed no macroscopic changes in nine rats. One eye of a single rat was found to be distended. In the absence of corroborative in-*life observations this finding was discounted as a toxic effect of the test article.

Interpretation of results:

GHS criteria not met

Conclusions:

Single oral administration 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 oral 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.

Executive summary:

A study was conducted according to OECD TG 420 and Directive 92/69/EEC method B1 bis to determine the acute toxicity of Incozol LV by oral gavage to rat. Therefore a preliminary test with 2 female rats at dose of 500 and 2000 mg/kg bw was performed. There were no deaths among pairs of female fasted rats following a single oral administration of Ineozol LV at either 500 or 2000 mg/kg bw. Thus, the main study was performed with 5 male and 5 female rats at 500 or 2000 mg/kg bw. The test item was dispersed in desiccated corn oil and administered at a dose volume of 10 mL/kg on Day 1. All animals were killed on Day 15 and subsequently underwent a full necropsy. No mortality was observed and there were no overt signs of reaction to treatment. All rats achieved body weight gains during the first and second weeks of the study. Necropsy revealed no macroscopic changes in nine rats. One eye of a single rat was found to be distended. In the absence of corroborative in-life observations this finding was discounted as a toxic effect of the test article. Single oral administration 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 oral 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

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:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

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:

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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

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.

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Additional information

Acute oral toxicity

A study was conducted according to OECD TG 420 and Directive 92/69/EEC method B1 bis to determine the acute toxicity of Incozol LV by oral gavage to rat. Therefore a preliminary test with 2 female rats at dose of 500 and 2000 mg/kg bw was performed. There were no deaths among pairs of female fasted rats following a single oral administration of Incozol LV at either 500 or 2000 mg/kg bw. Thus, the main study was performed with 5 male and 5 female rats at 500 or 2000 mg/kg bw. The test item was dispersed in desiccated corn oil and administered at a dose volume of 10 mL/kg bw on Day 1. All animals were killed on Day 15 and subsequently underwent a full necropsy. No mortality was observed and there were no overt signs of reaction to treatment. All rats achieved body weight gains during the first and second weeks of the study. Necropsy revealed no macroscopic changes in nine rats. One eye of a single rat was found to be distended. In the absence of corroborative in-life observations this finding was discounted as a toxic effect of the test article. Single oral administration 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 oral 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.

Acute inhalative toxicity

Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided.

Acute dermal toxicity

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.

Justification for classification or non-classification

The test item was tested for acute toxicity on oral administration and dermal administration. The acute oral LD50 was determined to be >2000 mg/kg bw. The acute dermal LD50 was determined to be greater than 2000 mg/kg bw. Based on the results of the studies, no classification and labelling for acute dermal and oral toxicity is necessary according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EC) 2017/776.