Oxazolidine, 3-butyl-2-(1-ethylpentyl)-

Endpoint summary

Description of key information

Oral

The acute oral toxicity study on Sprague-Dawley rats treated with Incozol 2 resulted in a LD50 of above 2000 mg/kg bw.

Dermal

The acute dermal toxicity study with Incozol 2 applied to the skin of male and female Sprague-Dawley CD rats resulted in a LD50 of greater than 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:

1995-11-10 to 1995-11-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 17th 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 31st 1992

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Weight at study initiation: male: 201-283 g; female: 165-190 g
- Fasting period before study: approximately 18 hours prior to dosing until 3 hours after dosing
- Housing: five animals per sex in suspended stainless steel mesh cages (dimensions 55 x 34 x 20 cm)
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

dessicated

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg bw
- Amount of vehicle: 10 mL/kg bw
- Lot/batch no.: 11362

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

five animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once within one-half hour of dosing, four times within four hours of dosing, twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
- body weight: was done on day -1 (day before dosing), day 1 (day of dosing), day 8 and day 15

Statistics:

NA

Preliminary study:

The preliminary study was undertaken to allow selection of the discriminating dose level for the main study. The discriminating dose level is the highest of four dose levels (5, 50, 500 or 2000 mg/kg) that is non-lethal in the main study. The preliminary investigation was conducted using groups of two fasted female rats dosed at 500 or 2000 mg/kg body weight.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died following single oral administration of Incozol 2 at 2000 mg/kg body weight.

Clinical signs:

other: There were no overt signs of reaction to treatment.

Gross pathology:

No macroscopic changes were apparent during necropsy of rats killed on day 15.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity study on Sprague-Dawley rats treated with Incozol 2 resulted in a LD50 of above 2000 mg/kg bw.

Executive summary:

This study was conducted to assess the acute oral toxicity of Incozol 2 in the rat (Sprague-Dawley). The method followed was in compliance with Method B.1 bis and OECD TG 420. Five male and five female fasted rats were given the test item as a single dose by oral gavage at the limit dose level of 2000 mg/kg body weight. The test item was dispersed in 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 animal died. There were no overt signs of reaction to treatment. All rats achieved body weight gains during the first and second week of the study. No macroscopic changes were apparent during necropsy of rats killed on day 15. The acute oral minimum lethal dose of Incozol 2 to rats was found to exceed 2000 mg/kg body weight (Corning Hazleton, 1995).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The available GLP study according to OECD/EU guideline is considered to be reliable without restrictions.

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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 data for a maximum of two routes of exposure need to be provided. Testing for acute toxicity via the inhalation route was not applicable as data on acute oral and acute dermal toxicity were available. Furthermore, the vapour pressure of Incozol 2 is with 2.5 Pa at 25 °C very low. An exposure with Incozol 2 is therefore very unlikely so the acute toxicity via inhalation was waived.

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:

2005-04-20 to 2005-05-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24th 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 31st 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: male: 230-246 g; female: 210-232 g
- Fasting period before study:
- Housing: individually (for the 24h exposure period) and in groups of five by sex (for the remainder of the study) in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Certified Rat and Mouse Diet (Code 5LF2), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.3 mL/kg
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days
- Necropsy of survivors performed: yes
- clinical signs: observed daily
- body weight: observed on day 1 and subsequently once a week

Statistics:

NA

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No signs of dermal irritation were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity study with Incozol 2 applied to the skin of male and female Sprague-Dawley CD rats has resulted in a LD50 of greater than 2000 mg/kg bw.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat according to OECD TG 402 and EU method B.3. A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths, no signs of systemic toxicity and no signs of dermal irritation. Further, all animals showed expected gains in bodyweight over the study period. The necropsy did not detect any abnormalities. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight (SafePharm Laboratories, 2005).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The available GLP study according to OECD/EU guideline is considered to be reliable without restrictions.

Additional information

Acute oral toxicity

A study was conducted to assess the acute oral toxicity of Incozol 2 in the rat (Sprague-Dawley). The method followed was in compliance with that described in Annex to Commission Directive 92/69/EC, Method B.1 bis and OECD Guidelines for Testing of Chemicals, Method 420 (1,2). Five male and five female fasted rats were given the test article as a single dose by oral gavage at the limit dose level of 2000 mg/kg body weight. The test article was dispersed in 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 animal died. There were no overt signs of reaction to treatment. All rats achieved body weight gains during the first and second week of the study. No macroscopic changes were apparent during necropsy of rats killed on day 15. The acute oral minimum lethal dose of Incozol 2 to rats was found to exceed 2000 mg/kg body weight. (Corning Hazleton, 1995)

Acute dermal toxicity

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat according to OECD TG 402 and EU method B.3. A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths, no signs of systemic toxicity and no signs of dermal irritation. Further, all animals showed expected gains in bodyweight over the study period. The necropsy did not detect any abnormalities. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight (SafePharm Laboratories, 2005).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.