2-dibutylaminoethanol

Endpoint summary

Description of key information

- Acute oral toxicity: LD50 > 550 - < 688 mg/kg (rat);
- Acute inhalation toxicity: 3 inhalation hazard tests, no mortality (rat);
- Acute dermal toxicity: LD50 1680 mg/kg bw (rabbit);

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented report which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(BASF test, no details on animal husbandry and weight development)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 255 g (mean males), 189 g (mean females)
No further data.

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion with traganth

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: The doses were administered as aqueous emulsions with traganth of 2% (200 mL/kg), 4% (400, 500, 640 mL/kg), 8% (800 mL/kg) and 20% (1600 mL/kg) test substance.

Doses:

200, 400, 500, 640, 800, 1600 mL/kg bw (172, 344, 430, 550, 688, 1376 mg/kg bw - conversion in mg/kg is based on the density: d= 0.8601 g/cm³).

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: daily
- Frequency of weighing: before the start of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 550 - < 688 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Corresponds to 640 / 800 mL/kg bw; the mg/kg was calculated by means of the density: d= 0.8601 g/cm³; 688 mg/kg bw: all animals died within 1 hour post application; 550 mg/kg bw: no animal died

Mortality:

688, 1376 mg/kg bw: all animals died within 1 hour post application
430, 550 mg/kg bw: no animal died
344 mg/kg bw: 1 female animal died within one hour post application
172 mg/kg bw: no animal died

Clinical signs:

other: 688, 1376 mg/kg bw: Immediately after application tremor, convulsion, sounds of pain, dyspnoea, secretion out of the oral cavity were observed until death. 430, 550 mg/kg bw: Immediately after application tremor, convulsion, sounds of pain, dyspnoea, secr

Gross pathology:

Animals that died: extended blood content in the liver and blood in the intestinal loops was observed.
Animals that were sacrificed at the end of the study: bronchitis and bronchiectasis (430, 550 mg/kg bw). No further abnormalities were detected.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

550 mg/kg bw

Quality of whole database:

Available data is reliable and sufficient for assessment.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

There are three Inhalation Hazard Tests available which all showed no mortalities in rats. Therefore, it is assumed that the whole database is sufficient for assessment and no further test is needed.

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:

other: Acceptable publication which meets basic scientific principles (limited informations).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

(occlusive dressing, no details on weight development, clinical signs, mortality)

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 to 3.5 kg
No further information.

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- % coverage: about 1/10 of the body surface
- Type of wrap if used: Impervious plastic film (Cuff method of Draize).

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not more than 20 ml/kg bw.

Duration of exposure:

24 hours

Doses:

No data.

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male

Dose descriptor:

LD50

Effect level:

1 680 mg/kg bw

Based on:

test mat.

95% CL:

1 200 - 2 360

Mortality:

No data.

Clinical signs:

other: No data.

Gross pathology:

No data.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 680 mg/kg bw

Quality of whole database:

Available data is reliable and sufficient for assessment.

Additional information

Acute oral toxicity

There are three studies available investigating acute oral toxicity of the test substance:

One BASF study (No. XVII/143, 1967) investigated acute toxic effects of the test substance after single oral administration to rats, similarly as adviced in OECD guideline 401. The test substance was administered once orally via gavage to 5 male and 5 female animals (no data on the strain) suspended in an aqueous emulsion with traganth at doses of 200, 400, 500, 640, 800, 1600 mL/kg bw (172, 344, 430, 550, 688, 1376 mg/kg bw - conversion in mg/kg is based on the density: d= 0.8601 g/cm³). Body weight was determined before administration. Clinical observations were performed at least once per day during the 14 days observation period and all animals were sacrificed and necropsied 14 days post administration. In the two higher dose groups (1376, 688 mg/kg bw) all animals died within 1 hour post application, 1 animal died in the 344 mg/kg bw dose group and no animals died in the 430, 550 and 172 mg/kg bw dose groups. Tremor, convulsion, sounds of pain, dyspnoea, secretion out of the oral cavity, reddened eyes, ruffled fur and accelerated respiration were observed. The surviving animals recovered within 2 to 5 days. No data on body weight change was given. At necropsy, extended blood content in the liver and blood in the intestinal loops was observed in the animals that died. In the animals, that were sacrificed at the end of the observation period, bronchitis and bronchiectasis (430, 550 mg/kg bw) were observed as the only abnormalities. The oral LD50 was determined to be > 550 - < 688 mg/kg body weight. 

The second BASF study (No. XV/127, 1965) also investigated acute toxic effects of the test substance after single oral administration to rats, similarly as adviced in OECD guideline 401. The test substance was administered once orally via gavage to 5 male and 5 female animals (no data on the strain) suspended in an aqueous emulsion with traganth at doses of 25, 200, 800, 1000, 1250, 1600, 2000, 2500 mL/kg bw (22, 172, 688, 860, 1075, 1376, 1720, 2150 mg/kg bw - conversion in mg/kg is based on the density: d= 0.8601 g/cm³). Body weight was determined before administration. Clinical observations were performed at least once per day during the 14 days observation period and all animals were sacrificed and necropsied 14 days post administration. All animals of the 2150, all male animals and 4 female animals of the 1720 mg/kg bw dose group died. 2 males and 2 females of the 1376 mg/dose group, 4 males and 2 females of the 1075 mg/kg bw dose group and 1 male as well as 1 female of the 688 mg/kg bw dose group died. No deaths were observed in the 860, 172 and 22 mg/kg bw dose groups. In the high dose levels, tremor, convulsion, sounds of pain, secretion out of the oral cavity were observed immediately after application, afterwards abdominal and lateral positioning and “morphin tails” (s-shaped tails). In the 22 and 172 mg/kg bw groups only agitated behavior was observed. The surviving animals recovered within 2-3 days. Data on body weight gain was not given. At necropsy, 1 animal of the 860 mg/kg bw dose groups showed bronchitis and atelectasis, no further clinical signs were observed. The oral LD50 was determined to be about 1075 mg/kg body weight.

In the study of Smyth et al. (1954), acute toxic effects of the test substance after single oral administration to rats was investigated. The documentation in this publication was very limited. The test substance was administered once orally via gavage to 5 male and 5 female animals (Carworth-Wistar rats) suspended in a not further specified vehicle (water, corn oil, or a 1 % solution of sodium 3,9-diethyl-6-tridecanol sulfate (Tergitol Penetrant 7)) at no further specified dose levels. Details on body weights/body weight development, mortality, clinical signs or gross pathology were not given. The oral LD50 was determined to be 1070 mg/kg body weight.

 

Acute inhalation toxicity

Three inhalation hazard tests investigating inhalation toxicity of the test substance are available:

In the first inhalation hazard test (IHT) by BASF (No. XVII/143, 1967), 6 male and 6 female rats were exposed to a test atmosphere saturated with vapours of test substance for 8 hours in two consecutive trials with 3 animals per trial. The test atmosphere was generated by bubbling 200 L/h dry air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder. The temperature in the exposure chamber was 20°C. The concentration of the test atmosphere was stated to be 0.15 mg/L, an analytical verification was not performed. As the calculated vapour saturation is 0.357 mg/L (vapour pressure: 0.05 hPa at 20°C), vapour saturation was eventually not completed. The animals were observed daily for 7 days for clinical signs and mortality. Weighing was performed only at the beginning of the study. No mortality resulted from the exposure to the test atmosphere. No clinical signs and no abnormalities at necropsy were observed.

In the second inhalation hazard test (IHT) by BASF (No. XV/127, 1965), 6 male and 6 female rats were exposed to a test atmosphere saturated with vapours of test substance for 8 hours in two consecutive trials with 3 animals per trial. The test atmosphere was generated by bubbling 200 L/h dry air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder. The temperature in the exposure chamber was 20°C. The concentration of the test atmosphere was stated to be 0.54 mg/L, an analytical verification was not performed. As the calculated vapour saturation is 0.357 mg/L (vapour pressure: 0.05 hPa at 20°C), aerosol formation could not be excluded. The animals were observed daily for 7 days for clinical signs and mortality. Weighing was performed at the beginning and end of the study and the animals gained body weight. No mortality resulted from the exposure to the test atmosphere. No clinical signs and no abnormalities at necropsy were observed.

Smyth et al. (1954) investigated the inhalative toxicity by exposing 6 male and 6 female rats to a flowing stream of air approaching saturation with vapours for 8 hours. The stream was prepared by passing dried air through a fritted disc gas washing bottle initially at room temperature (analytical verification was not performed). No mortality was observed. Data on clinical signs, body weights or necropsy were not given.

Thus, all three Inhalation Hazard Tests conducted indicating that a saturated atmosphere at ambient temperature does not induce mortality. Therefore, there is no need to conduct further inhalation studies for the determination of an acute LC50 after exposure to vapours of the test substance.

 

Acute dermal toxicity

In the study by Smyth et al. (1954) acute dermal toxicity study was investigated. New Zealand White rabbits (4 males) were dermally exposed to a single, but not further specified dose of the test substance (1/10 of the body surface, covered by occlusive dressing) for 24 hours. The animals were observed for 14 days. No data on mortality, clinical signs, body weights or necropsy were given. The acute dermal median lethal dose (LD50) was determined to be 1680 (1200 - 2360) mg/kg bw in rats.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for acute oral toxicity (Xn, R22), and for dermal toxicity (Xn, R21) is warranted.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute oral toxicity (Cat. 4), and for dermal toxicity (Cat. 4) is warranted.