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Description of key information

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:
1953
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
A sample of di (2-ethylhexyl) ethanolamine (S-5223) was received from S. Charleston on 11-12-52 for toxicological assay.
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
Carworth-Wistar, non-fasted rats, 5 to 6 weeks of age and 90-120 grams in weight were dosed at levels differing by a factor of 2.0 in a geometric series. The rats were reared in our own colony and maintained from time of weaning on Rockland rat diet (complete).
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Single doses of test material were given by stomach tube to non-fasted male albino rats by mouth as a dilution in corn oil, 1 ml = .010 gm.
Doses:
Dosage (gm/kg): 2.00, 3.98 and 7.95
No. of animals per sex per dose:
5 males/dose group
Control animals:
no
Details on study design:
Animals were weighed prior to dosing and at the end of the 14-day observation period.
Statistics:
Thompson's method of calculating the median-effective dose (LD50) was applied to the 14-day mortality data. For calculation of the LD50 by the method of moving averages the death of 5 of 5 rats was assumed at 15.8 gm/kg.
Sex:
male
Dose descriptor:
LD50
Effect level:
4 900 mg/kg bw
Based on:
test mat.
Remarks:
10% dilution in corn oil.
Mortality:
The rats that were dosed at 7.95 gm/kg died within 1 to 5 days; 1 rat from the 3.98 gm/kg group died on day 3. All other rats survived.
Clinical signs:
The rats that survived 3.98 gm/kg lost their hair in patches over their bodies.
Body weight:
All animals surviving the 14-day observation period gained weight with the exception of one animal in the 3.98 gm/kg dose group. This animal lost 13 g by the end of the observation period.
Gross pathology:
Autopsy findings on those that died included congested lungs, mottled livers, pale spleens and kidneys, and irritation of the intestines.
Other findings:
Butyl ethanolamine, for comparison, had an LD50 of 1.2 gm/kg, Phenyl 2.2, isopropanolamines (mixed) 4.5 and dihydroxyethyl ethylene diamine 10.0 gm/kg.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for Wistar rats, given a 10% dilution in corn oil of the test material Di(2 -Ethylhexyl) ethanolamine by stomach tube, was 4.9 (3.8 to 6.5) gm/kg.
Executive summary:

Single doses of test material were given by stomach tube to non-fasted male albino rats by mouth as a dilution in corn oil, 1 ml = .010 gm. Five males/dose group were given 2.00, 3.98 or 7.95 gm/kg. Animals were weighed prior to dosing and at the end of the 14-day observation period. Thompson's method of calculating the median-effective dose (LD50) was applied to the 14-day mortality data. The rats that were dosed at 7.95 gm/kg died within 1 to 5 days; 1 rat from the 3.98 gm/kg group died on day 3. All other rats survived. The rats that survived 3.98 gm/kg lost their hair in patches over their bodies. All animals surviving the 14-day observation period gained weight with the exception of one animal in the 3.98 gm/kg dose group. This animal lost 13 g by the end of the observation period. Autopsy findings on those that died included congested lungs, mottled livers, pale spleens and kidneys, and irritation of the intestines. Butyl ethanolamine, for comparison, had an LD50 of 1.2 gm/kg, Phenyl 2.2, isopropanolamines (mixed) 4.5 and dihydroxyethyl ethylene diamine 10.0 gm/kg.

The LD50 for Wistar rats, given a 10% dilution in corn oil of the test material Di(2 -Ethylhexyl) ethanolamine by stomach tube, was 4.9 (3.8 to 6.5) gm/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 900 mg/kg bw
Quality of whole database:
sufficient

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1953
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
A sample of di (2-ethylhexyl) ethanolamine (S-5223) was received from S. Charleston on 11-12-52 for toxicological assay.
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
Male albino New Zealand strain rabbits, 3 to 5 months of age and averaging 2.5 kg in weight were utilized in the study. The rabbits were procured locally and maintained on Rockland rabbit ration.
Type of coverage:
other: "Vinylite" sheeting was used to retain the dose in contact with the clipped skin.
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The rabbits were immobilzed during the 24 hour skin contact period. Thereafter, the "vinylite" sheeting used to retain the dose in contact with the clipped skin of the trunk was removed and the animals were caged for the remainder of the 14-day observation period.
Duration of exposure:
24 hours
Doses:
Dosage (ml/kg): 0.63, 1.26, 2.52, 5.0
No. of animals per sex per dose:
Four animals per dose with the exception of the 0.63 ml/kg group which only had one animal.
Control animals:
no
Details on study design:
Animals were weighed prior to dosing and at the end of the 14-day observation period.
Statistics:
Thompson's method of calculating the LD50 was used. For calculation of the LD50 by Thompson's method the survival of 3 rabbits was assumed for 0.63 ml/kg.
Sex:
male
Dose descriptor:
LD50
Effect level:
2.5 mL/kg bw
Based on:
test mat.
Mortality:
Three of the four animals dosed in the 2.52 and the 5.0 ml/kg dose groups died. All other animals survived.
Clinical signs:
Erythema and desquamation of the skin was caused by the application.
Body weight:
All but one animal lost weight during the course of the study. One animal in the 5.0 ml/kg dose group gained weight.
Gross pathology:
Lung damage was severe among those dying and livers were mottled.
Other findings:
This compound penetrates skin readily as may be seen by comparing these results with methyl diethanolamine which had a rat oral LD50 of 1.8 gm/kg and rabbit skin penetration LD50 of 11.9 ml/kg.
Conclusions:
The undiluted compound had an LD50 for rabbits of 2.5 (1.3 to 4.8) ml/kg.
Executive summary:

In a skin penetration study conducted on male albino New Zealand rabbits, the undiluted test material was applied using "vinylite" sheeting to the clipped skin of the trunk of the animals for a 24 hour exposure period at either 0.63, 1.26, 2.52 or 5.0 ml/kg. Animals were weighed prior to dosing and at the end of the 14-day observation period. Thompson's method of calculating the LD50 was used. Three of the four animals dosed in the 2.52 and the 5.0 ml/kg dose groups died. All other animals survived. Erythema and desquamation of the skin was caused by the application. All but one animal lost weight during the course of the study. One animal in the 5.0 ml/kg dose group gained weight. Lung damage was severe among those dying and livers were mottled. The undiluted compound had an LD50 for rabbits of 2.5 (1.3 to 4.8) ml/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
sufficient

Additional information

In a rat acute oral toxicity study (pre-dating guideline and GLP), 15 Carworth-Wistar male rats (5 per dose group, 3 dose groups), were dosed via gavage with the test material in Corn oil (10% dilution).

The LD50 was determined to be 4.9 gm/kg. rats dosed at 7.95 gm/kg died within 1 -5 days. Rats surviving at the next lowest dose, 3.98 gm/kg lost their hair in patches. Autopsy of the rats that died identified congested lungs, mottled livers, pale spleens and kidneys and irritation of the intestines.

In a rabbit acute dermal toxicity study, the test material was dosed undiluted via the skin under an occlusive dressing to 16 rabbits, (5 per dose for the 1.26, 2.52 abd 5 ml/kg and 1 per dose at the 0.63ml/kg dose). The LD50 was determined to be 2.5 gm/kg.

Observations during the study included erythema and desquamation of the skin. Gross pathology identified mottled livers and lung damage.

Justification for classification or non-classification

The acute oral and dermal LD50s are >2000 mg/kg bw - therefore classification criteria for acute toxicity are not met.