4-(1-oxo-2-propenyl)-morpholine

Endpoint summary

Description of key information

The acute median lethal oral dose LD50 of the substance to rats is estimated to be 588 mg/kg bw for males and females combined.
The acute median lethal dermal dose LD50 of the substance to rats was found to be greater than 2000 mg/kg bw.
The acute inhalation study with snout-only exposure resulted 4-hour LC50 of >5.28 mg/L.

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 22 April to 15 May 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Batch number: 6032505
Purity: not specified

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 91 to 138 g
- Fasting period before study: overnight prior to and 4 hours after dosing
- Housing: housed in groups by sex in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C, max 23°C
- Humidity (%): 57%
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.9 mL/kg

Treatment procedure: The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.

Doses:

400, 500, 640, 1000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed soon after dosing, then at frequent intervals for remainder of day 1. On subsequent days the animals were observed once in the morning and again at end of experimental day. The following were recorded: approximate time of death of inidividual rats; the nature, severity, approximate time of onset and duration of each toxic sign; individual bodyweights of rats on days 1, 8 and 15 and at death.
- Necropsy of survivors performed: yes
Surviving animals were killed on day 15 by carbon dioxide asphyxiation. All animals that died during the study and those killed on day 15 were subjected to a macroscopic post mortem examination which consisted of opening the abdominal, thoracic and cranial cavities. The macroscopic appearance of abnormal organs when present was recorded.

Statistics:

The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney (1971) Probit analysis (3rd edition) Cambridge University press.

Preliminary study:

A trial test was carried out to establish a dosing regimen using groups of two male and two female rats at three dose levels of 500, 1000 and 2500 mg/kg bodyweight.
Results indicated that the acute median lethal oral dose of the substance was between 500 and 1000 mg/kg bodyweight.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

588 mg/kg bw

Based on:

test mat.

95% CL:

> 524 - < 701

Mortality:

Mortalities occurred among male rats dosed at 500 mg/kg and above and among females dosed at 640 or 1000 mg/kg. Deaths occurred from five hours after dosing until day 4.

Clinical signs:

other: piloerection, abnormal body carriage, abnormal gait, lethargy, decreased respiratory rate, pallor of extremeties and increased salivation

Body weight:

other body weight observations

Remarks:

normal bodyweight gain for survival animals

Gross pathology:

The autopsy of the rats which died during the study showed
in almost all rats a pallor of kidneys, spleen and/or liver.
The autopsy of the animals sacrificed at the end of the
study did not show deviations.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute median lethal oral dose LD50 of the substance to rats is estimated to be 588 mg/kg bw for males and females combined.

Executive summary:

The study is performed to assess the acute oral toxicity of the substance, according to OECD Guideline 401.

The acute median lethal oral dose LD50 of the substance to rats is estimated to be 588 mg/kg bw for males and females combined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

588 mg/kg bw

Quality of whole database:

reliable without restrictions

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 03 to 24 July 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Specific details on test material used for the study:

Lot No.: 06512330
Purity: 99.5%

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
- Age at exposure: 8-12 weeks
- Weight at study initiation: ca 200 g
- Housing: the rats were housed by sex in groups of 5, the holding cages were made of stainless steel sheet and wire mesh and were suspended on a moveable rack.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50%

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

snout only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 3.1 - <= 3.2 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: snout-only exposure chamber (ADG developments)
- Exposure chamber volume: 30 L
- Source and rate of air (airflow): 0.15 mL/minute
- Method of conditioning air: A supply of clean dried air was connected to aerosol generator and supply pressure was adjusted to give a flow rate of 10 L/min measured at generator outlet tube.
- System of generating particulates/aerosols: The aerosol generator was designed to produce and maintain an atmosphere containing a high proportion of respirable droplets. All parts of the generator in contact with the test substance were made of stainless steel or glass. The test substance was supplied to the generator from a syringe driven at a constant rate by a syringe pump. The compressed air supply to the generator was dried, filtered and oil-free.
- Temperature, humidity, pressure in air chamber: Temperature (°C): 22°C, Humidity (%): 54-66%

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: at least five air samples were taken from chamber during each 4-hour exposure and the collected material was weighed to determine the concentration of test substance in chamber air. Each air sample was withdrawn at 2 L/min, through a weighed Whatman GF/A glass fibre filter, held in an open face filter holder. The volume of air samples were measured with a wet-tupe gas meter. One or two additional air samples were taken during each exposure using a Marple cascade impactor, to determine particle size distribution.
- Samples taken from breathing zone: yes/no
- Time needed for equilibrium of exposure concentration before animal exposure: 7 minutes is theoretical time required for concentration of aerosol in chamber to reach 90% of its final value

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.3, 5.28 mg/L

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed continuously during exposure for signs of reaction to test substance and at least twice daily during observation period. All rats were weighed daily from day of delivery until end of observation period. Food and water comsumption were determined daily for each cage of rats by weight loss from the food hoppers and water bottles.
- Necropsy of survivors performed: At the end of 14-day observation period rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination. Rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate lung weight to bodyweight ratio. The lungs were infused with and preserved in buffered 10% formalin together with samples of liver and kidneys for possible future microscopic examination.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.28 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no death.

Clinical signs:

other: no treatment-related signs during exposure, soiling of fur with excreta was seen in all test and control rats during exposure; immediately following exposure fascicular tremors were seen in rats together with exaggerated respiratory movements

Body weight:

Small bodyweight loss were recorded at 3 days following exposure for 4 hours.

Gross pathology:

All animals were within normal limits.

Interpretation of results:

GHS criteria not met

Conclusions:

The 4-hour LC50 for the substance is determined as in excess of 5.28 mg/L.

Executive summary:

The acute inhalation toxicity of the substance was assessed by exposing groups of rats, with snout-only exposure. The 4-hour LC50 for the substance is determined as in excess of 5.28 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5.28 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

reliable without restrictions

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 16 April to 13 May 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Lot No.: 6032505
Purity: not specified

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 200 to 250 g
- Housing: housed individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C, max 23°C
- Humidity (%): 57%
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsolumbar region of each rat
- % coverage: 10% of total body surface
- Type of wrap if used: gauze was held in place with an impermeable dressing encircled firmly around trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water and blotted dry with absorbent paper
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.87 mL/kg

Duration of exposure:

24 hours

Doses:

1260, 2000, 3200 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed soon after dosing, then at frequent intervals for remainder of day 1. On subsequent days the animals were observed once in the morning and again at end of experimental day. The treated areas of skin were examined daily for sign of dermal irritation and assessed.
The following were recorded: approximate time of death of inidividual rats; the nature, severity, approximate time of onset and duration of each toxic sign; individual bodyweights of rats on days 1, 8 and 15 and at death.
- Necropsy of survivors performed: yes
Surviving animals were killed on day 15 by cervical dislocation. All animals that died during the study and those killed on day 15 were subjected to a macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two female rats dosed at 2000 mg/kg bw were found dead on day 2. There was no death in groups of rats dosed at 1260 and 3200 mg/kg bw.

Clinical signs:

other: no signs of systemic reaction to treatment

Body weight:

other body weight observations

Remarks:

Body weight gains were reduced on day 8 in most of theanimals, especially in that which received 2000 or 3200mg/kg.

Gross pathology:

In the animals which died during the study: unregullar areas of pallor in the liver.

Other findings:

none

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal dermal dose LD50 of the substance to rats was found to be greater than 2000 mg/kg bw.

Executive summary:

The study is performed to assess the acute dermal toxicity of the substance, according to OECD Guideline 402.

The acute median lethal dermal dose LD50 of the substance to rats was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

reliable without restrictions

Justification for classification or non-classification

Acute toxicity:
Oral LD50 is 588 mg/kg body weight；
Dermal LD50 > 2000 mg/kg bw;

Inhalation LC50: >5.28 mg/L.
Therefore, in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1, this substance should be classified as Cat 4 for acute oral endpoint, and should not be classified for acute inhalation and dermal endpoints.

Specific target organ toxicity-single exposure:
Oral:
Pallor of kidneys, spleen and/or liver showed in almost all died animals, while normal in all survived animals.
Inhalation:
Stowed lungs showed in all died animals, while normal in all survived animals.
As there were no effects considered to support classification for Category 1 and 2 observed. Therefore, in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1 and 3.8.2, this substance should not be classified.