2,2'-oxydi(ethylamine)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Two instead of five animals per sex per dose are used. At half of the test animals, the skin is abraded before application of the test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Two instead of five animals per sex per dose are used. At half of the test animals, the skin is abraded before application of the test substance.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-oxydi(ethylamine)

EC Number:

220-395-5

EC Name:

2,2'-oxydi(ethylamine)

Cas Number:

2752-17-2

Molecular formula:

C4H12N2O

IUPAC Name:

2-(2-aminoethoxy)ethan-1-amine

Specific details on test material used for the study:

- Name of test material (as cited in study report): 5601-22-1, Order #J-169
- Substance type: clear liquid
- Physical state: liquid
- Base factor: 1.047 gm/ml
- Purity: responsibility of the sponsor
- Other: stability: there was no apparent change in the physical state of the test article during administration

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Douglasseville, Pennsylvania and Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2 to 3 kilograms
- Housing: Separate isolation by test system
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering.
- Water (e.g. ad libitum): Availability - fresh tap water, fit for human consumption, ad libitum using 16 ounce glass bottles with rubber stopper and stainless steel sipper tube or an automatic watering system supplied by Edstrom Industries, Inc., Waterford, Wisconsin.
- Acclimation period: five days

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

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shaved trunk
- % coverage: no less than 20% of the dorsal body surface area
- Type of wrap if used: The test article was applied directly onto the exposed skin of the animals taking care to spread the substance evenly over the entire abraded area. A layer of gauze was wrapped around the animals to cover the dosed area. The animals were wrapped with rubber dam and an ace bandage to retard evaporation. The test article was held in contact with the skin for twenty-four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following the twenty-four hour period of exposure, the rubber dam and ace bandage were removed. The test site was washed to remove any remaining material.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 quart

Duration of exposure:

24 hours

Doses:

2500, 3200, 4000, 5000, 6300 and 8000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days: Observations were recorded at 30 minutes, 2 and 4 hours after the 24 hour period of exposure, and twice daily thereafter for fourteen days. All rabbits were sacrificed by CO2 inhalation on Day 14 and a gross necropsy was performed.

Statistics:

By the method of Litchfield and Wilcoxon (1949).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 550 mg/kg bw

Based on:

test mat.

95% CL:

2 530 - 4 980

Mortality:

Dose-range finding study: None of the rabbits died at the 1000 mg/kg dose level. One of two rabbits died at the 3000, 5000 and 8000 mg/kg dose levels.
Dermal LD50 determination:
None of the rabbits died at 2500 mg/kg, two of four rabbits died at 3200 mg/kg, four of four died at 4000 mg/kg, two of four at 5000 mg/kg and four of four died at the 6300 and 8000 mg/kg dose levels.

Clinical signs:

other: Dose-range finding study: Signs included necrosis, slight edema, ataxia, decreased activity, bleeding from the anal and genital areas, body drop, diarrhea, abnormal gait, abnormal stance and decreased body tone. Dermal LD50 determination: Signs observed

Gross pathology:

Necropsy of the animals dying on the study revealed dark discolorations and hemorrhages at the application sites, pale kidneys, dark red fluid-filled bladders and pale livers with multiple small irregular yellow nodules, hemorrhages in the cortex of both kidneys, fluid-filled intestines and erosions in the stomach mucosa. Fluid in the thoracic cavity, discolored adrenals, distended bladders, congested lungs and distended fluid-filled intestines were also observed. Terminal necropsy revealed hemorrhages of the muscle layers under the application sites, fluid in the abdominal cavity, liver adhered to abdominal walls, kidneys pitted with surface hemorrhages and small areas of necrosis on the skin sites.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the observations made in the Acute Dermal Toxicity Study in Rabbits, the calculated dermal LD50 for the test substance was determined to be 3550 mg/kg with 95% confidence limits of 2530 to 4980 mg/kg. Based on the test results and according to the criteria of the CLP Regulation, the substance should not be classified for acute dermal toxicity.