3-morpholinopropylamine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-10-30 to 1993-01-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-morpholinopropylamine

EC Number:

204-590-2

EC Name:

3-morpholinopropylamine

Cas Number:

123-00-2

Molecular formula:

C7H16N2O

IUPAC Name:

3-morpholin-4-ylpropan-1-amine

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: no data
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: no data
- Solubility and stability of the test substance in the solvent/vehicle: not provided

OTHER SPECIFICS:
- Specific gravity: 0.9888 g/mL

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Denver PA
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 2.430 - 3.131 kilograms
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow H.F.®, checked daily and added or replaced as needed according to standard Operating Procedure PH-113.
- Water (e.g. ad libitum): Fresh tap water, ad libitum.
- Acclimation period: Minimum of five (5) days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°c ± 3°C
- Humidity (%): 30 to 70%.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark.

Administration / exposure

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: no data
- Type of wrap if used: The test article was applied directly onto the exposed intact skin of the animals taking care to spread the substance evenly over the entire area. A square gauze patch was placed on the animals to cover the dosed area. The animals were wrapped with a rubber dam and an elastic bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following the twenty-four hour period of exposure, the wrappings were removed and the skin sites were wiped with water and gauze to remove any residual test article.
- Time after start of exposure: The test article was applied once and remains in contact with the skin site for twenty-four hours.

Duration of exposure:

Administered once and remained in contact with the skin site for twenty-four hours.

Doses:

1000, 2000 and 3000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were recorded daily through Day 14. Body weights were recorded at initiation and on Days 7 and 14 or when found dead.
- Necropsy of survivors performed: yes, on Day 14

Statistics:

By the method of Litchfield and Wilcoxon via the Innovative Programming Associates, LABCAT Module Version 4.24.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 219.7 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 396.1 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 297.9 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died at the 1000 mg/kg dose level.
Three of ten animals died at the 2000 mg/kg dose level and eight of ten animals died at 3000 mg/kg.

Clinical signs:

Clinical signs observed included decreased activity, abnormal gait, abnormal stance, decreased muscle tone, dyspnea and prostration.
Necrosis and/or sloughing of the skin at the application site was also observed during the study.

Body weight:

There was an apparent decrease in mean body weight of both males and females during the course of the study.

Gross pathology:

Necropsy of the animals that died on study revealed distended stomach and intestines, discolored kidneys, lungs and liver and necrosis of the skin at the application site. At terminal necropsy, necrosis of the skin at the application site was observed in all animals. No other visible lesions were observed in any animal at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the observations made in the Acute Exposure Dermal Toxicity study in rabbits, the definitive acute dermal LD50 in males, females and combined sexes was determined to be 2219.7, 2396.1 and 2297.9 mg/kg respectively. Based on these LD50 values and the criteria of the CLP Regulation, the test item should not be classified for acute dermal toxicity.