2,2'-oxydi(ethylamine)

Endpoint summary

Description of key information

Acute toxicity - oral: A K1 acute oral toxicity test was performed in male and female Sprague Dawley rats according to a guideline similar to OECD Guideline 401 (Mallory VT, 1983). 
Acute toxicity - inhalation: An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (according to REACH, Annex VIII section 8.5, column 2). In addition, acute oral and acute dermal toxicity studies with the test substance are available.
Acute toxicity - dermal: A K1 acute dermal toxicity test was performed in male and female New Zealand White rabbits according to a guideline similar to OECD Guideline 402 (Mallory VT, 1983).

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:

1983-08-22 - 1983-09-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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
- Purity: responsibility of the sponsor
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration.
- Other: Specific gravity - 0.955 gm/mL

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York or Hilltop Lab Animals, Inc. Scottdale, Pennsylvania
- Weight at study initiation: 180 - 360 grams after fasting. The weight variation in animals or between groups did not exceed ± 20%
- Fasting period before study: yes
- Housing: Separate isolation by test system.
- Diet (e.g. ad libitum): Wayne Lab Blox, 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 an automatic watering system supplied by Edstrom Industries, Inc. Waterford, Wisconsin.
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data

Doses:

400, 630, 1000, 1250 and 1600 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: The rats were observed at approximately 1, 2, 4 and 24 hours after dosing and twice daily for 14 days for pharmacotoxic, CNS effects and mortality. On days 7 and 14, body weights were recorded.
- Necropsy of survivors performed: yes. The surviving rats were sacrificed by CO2 inhalation and a gross necrospy performed.

Statistics:

According to the method of Litchfield and Wilcoxon (1949).

Preliminary study:

Dose-range finder with 4 rats (2 males, 2 females) per concentration indicated:
1000 mg/kg: 3/4 died; 2000, 4000 and 8000 mg/kg: all rats died.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

961 mg/kg bw

Based on:

test mat.

95% CL:

>= 746 - <= 1 239

Mortality:

400 mg/kg: 1 male died after 1 day
630 mg/kg: no mortality
1000 mg/kg: 1 male and 2 females died after 1 day, 1 female died after 2 days
1250 mg/kg: 2 males died after 1 day, 1 male after 2 days and 1 male after 11 days; 5 females died after 1 day
1600 mg/kg: 3 males died after 1 day and 1 male died after 5 days; 5 females died after 1 day

Clinical signs:

other: Signs observed included decreased body tone and activity, poor grooming, piloerection, salivation, lacrimation, abnormal gait and stance, cyanosis, hypersensitivity, body drop, semi-prostration, diarrhea, dyspnea and prostration.

Gross pathology:

Necropsy of the animals dying on study revealed stomach and intestines fluid-filled and hemorrhagic. The lungs were congested and edematous. Discolored testes and spleen, pancreas, ulcers of the stomach, hydrothorax and hemorrhages of testicular connective tissue were also observed. Terminal necropsy revealed no visible lesions in any of the remaining animals.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based upon the results of the acute oral toxicity study in rats, the calculated acute oral LD50 for male and female rats treated with the test substance was determined to be 961 mg/kg with confidence limits of 746 to 1239 mg/kg. Based on the results of this study and according to the CLP criteria, this substance should be classified as acute oral toxic category 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

961 mg/kg bw

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 the substance is classified as corrosive to the skin

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

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.

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

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

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

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).

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 550 mg/kg bw

Additional information

Acute toxicity: oral

Mallory VT (1983) investigated the acute oral toxicity via gavage of 400, 630, 1000, 1250 and 1600 mg/kg bw of the test substance in male/female Sprague-Dawley rats (5 animals per sex and per dose) (K1, key study). At 400 mg/kg, 1 male died after day 1; at 630 mg/kg, no mortality was observed; at 1000 mg/kg, 1 male and 2 females died after 1 day, 1 female died after 2 days; at 1250 mg/kg, 2 males died after 1 day, 1 male after 2 days and 1 male after 11 days; 5 females died after 1 day; at 1600 mg/kg, 3 males died after 1 day and 1 male died after 5 days, 5 females died after 1 day. The calculated acute oral LD50 for male and female rats treated with the test substance was determined to be 961 mg/kg with confidence limits of 746 to 1239 mg/kg. Clinical signs observed included decreased body tone and activity, poor grooming, piloerection, salivation, lacrimation, abnormal gait and stance, cyanosis, hypersensitivity, body drop, semi-prostration, diarrhea, dyspnea and prostration. Necropsy of the animals dying on study revealed stomach and intestines fluid-filled and hemorrhagic. The lungs were congested and edematous. Discolored testes and spleen, pancreas, ulcers of the stomach, hydrothorax and hemorrhages of testicular connective tissue were also observed. Terminal necropsy revealed no visible lesions in any of the remaining animals.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (Regulation (EC) No 1907/2006, Annex VIII section 8.5). In addition, an acute oral and acute dermal toxicity studies are available.

Acute toxicity: dermal

Mallory VT (1983) investigated the acute dermal toxicity of the test substance BAEE in New Zealand White male/female rabbits (2 animals per sex and per dose) after 24 hours of exposure to either 2500, 3200, 4000, 5000, 6300 or 8000 mg/kg bw (K1, key study). After 14 days of observation, the calculated dermal LD50 for BAEE was 3550 mg/kg with 95% confidence limits of 2530 to 4980 mg/kg. 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 observed included: vocalizations, necrosis, decreased activity, decreased body tone, bleeding from the anal and genital areas, body drop, abnormal stance, abnormal gait, semiprostration, poor grooming, erythema and edema of the application sites, prostration, cyanosis and abnormal head position. 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.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and according to the criteria laid down in the CLP Regulation, the test substance should be classified as an acute oral toxicant category 4 (H302).

Based on the available data and according to the criteria laid down in the CLP Regulation, the test substance should not be classified for acute dermal toxicity.

No data were available to decide on the classification for the inhalation route.