N,N-diethyl-2-propynylamine

Endpoint summary

Description of key information

Oral: LD50 = ca. 472 mg/kg bw (rat, test similar to OECD 401)

Dermal: LD50: 460 mg/kg bw (rabbit)

Inhalation: LC50 = 2100 mg / m3 (rat, 4h, test similar to OECD 403)

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:

Not specified

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)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Name of the test substance used in the study report: Golpanol DEP = 1-Diethylaminopropin

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Mean body weight: males: 193 g; females: 163 g
- The animals were offered a standardized animal laboratory diet (Altromin R 1324, Altromin GmbH, Lage, Germany)

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

- Emulsion in 0.5% aqueous CMC preparation with 2 - 3 drops Cremophor EL
- Test concentrations: 3.16, 4.64, 5.62, 6.81, 12.1, 14.7, 17.8 and 21.5% (V/V)

Doses:

316, 464, 462, 681, 1210, 1470, 1780 and 2150 µL/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 472 mg/kg bw

Remarks on result:

other: original value: 590 µL/kg

Mortality:

- At doses 316 and 464 µL/kg: no deaths after 14 days
- At dose 562 µL/kg: 4/10 deaths after 14 days
- At dose 681 µL/kg: 8/10 deaths after 14 days
- At all higher dose levels: 10/10 deaths after 14 days

Clinical signs:

other: Dyspnea, apathy, abdominal position, staggering, partly atony, twitching, trembling, partly biting convulsions, partly clonic convulsions, cyanosis, partly lacrimation, poor general state.

Gross pathology:

- 2150 µL/kg: limited bloating and pneumonic areas in the lungs
- 1210-1780 µL/kg: Heart: acute dilatation, specifically at the richt side; acute congestive hyperemia
- 681 µL/kg: Pneumonic areas in one animal
- 562 µL/kg: heart: acute dilatation, specifically of the atrium; stomach: congestive, thin content.

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

472 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

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 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

- Name as used in study report: Golpanol DEP; Diethylaminopropin
- Physical: clear yellowish liquid
- Purity: 99%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Mura: SPRA (SPF 68 Han), Firma MUS RATTUS, Brunnthal,
- Body weight range: 185 ± 15 g
- The animals were offered Herilan MRH of H. EGGERSMANN KG, Rinteln/Weser, and tap water ad libitum during the post-exposure observation period.
- The animals were kept in fully air-conditioned rooms (temperature 22 ± 2°C and humidity 55 ± 5%) with a day/night rhythm of 12 hours.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

- A concentration estimated on the basis of the data from the inhalation hazard test was used as a first orienting concentration. A concentration allows a no effect level to be established (0 lethality).
- Dynamic inhalation system. Whole-body inhalation system (groups of 5 animals are placed in wire cages which are located in a glass-steel inhalation chamber, V = 200 L)
- Generator system: Continuous infusion pump UNITA I; glass evaporator with thermostat
- By means of a continuous infusion pump, constant amounts of the test substance were supplied to an evaporator heated to 49°C. The vapors that were formed were mixed with a flow of fresh air and passed into the inhalation chamber.
- By means of an exhaust air system, the pressure ratios in the inhalation system were adjusted in such a way that there was a pressure slightly below the atmospheric pressure (negative pressure) .

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

- Analytical concentrations: 0.60, 1.54, 1.86, 2.64, 5.95 mg/L
- Nominal concentrations: 1.60, 4.02, 5.35, 8.03, 9.64 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- After the exposure period, the surviving animals were observed for 14 days.
- The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. The absolute body
weight gain and the relative body weight gain (difference in weight between the initial weight of the animals and the following weights) were determined from the values and presented graphically.
- Clinical findings and lethality were recorded daily.
- At the end of the 14-day observation period, the animals were sacrificed with C02 and were subjected to a gross-pathological examination like all other animals which had died before.

Statistics:

The statistical evaluation of the experiment was based on a probit analysis by D.J. Finney (D. J. Finney; Probitanalysis 1971, page 1 - 150, publisher: Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1.)

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.1 mg/L air

Exp. duration:

4 h

Mortality:

- 0.6 (1.6) mg/L and 1.54 (4.02) mg/L: no deaths;
- 1.86 (5.35) mg/L: 5/10 male and 5/10 females dead animals
- 2.64 (8.03) mg/L: 7/10 male and 8/10 females dead animals
- 9.64 (5.95) mg/L: 10/10 male and 10/10 female dead animals

Clinical signs:

other: - All dose groups: watery eye/nasal secretion (partly reddish), eyelid closure, salivation, intermittent breathing, crouching position, abdominal position, twitching, trembling rsp. clonic convulsions, apathy, staggering gait, ruffled fur. - All symptoms

Body weight:

- Males showed no abnormalities in the body weight growth (compared with the control group).
- Female animals of the test group 2 (2.64 resp. 8.03 mg/L) showed a reduced body weight gain.

Gross pathology:

Animals that died:
- Heart: acute dilatation of the atrium;
- Acute congestive hyperemia;
- Lung: intense blood filling with slight edema;
- Liver: broadened, loam-brown liver lobe periphery; partly liver with lateral corrugation.

Sacrificed animals:
- Nothing abnormal detected.

Interpretation of results:

Category 3 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2 100 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

Principles of experimental methods according to Smyth and Carpenter (1944, 1948); Smyth et al. 1949, 1951, 1954, 1962, 1969).

GLP compliance:

no

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Control animals:

not specified

Key result

Dose descriptor:

LD50

Effect level:

460 mg/kg bw

Remarks on result:

other: Original information: LD50 = 570 µL/kg

Interpretation of results:

Category 3 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

460 mg/kg bw

Additional information

Acute toxicity: oral

The test substance was tested based on internal BASF protocol on Sprague-Dawley rats (males / females), which is similar to OECD TG 401 (BASF, 1976). The rats were orally administrated (gavage) at doses 316, 464, 462, 681, 1210, 1470, 1780 and 2150 µL/kg. The animals were observed for 14 days. Clinical signs, body weights and necropsy was performed. No deaths were observed after 14 days at doses of 316 and 464 µL/kg. At the dose of 562 µL/kg, 4/10 deaths were observed after 14 days. At the dose of 681 µL/kg, 8/10 deaths were observed after 14 days. While at all higher dose levels, 10/10 deaths were observed after 14 days. The following clinical signs were observed: dyspnea, apathy, abdominal position, staggering, partly atony, twitching, trembling, partly biting convulsions, partly clonic convulsions, cyanosis, partly lacrimation, poor general state. No abnormal effects were observed in body weight gain. Gross pathology revealed acute dilatation in the heart and acute congestive hyperemia. The LD50 was determined to be 472 mg/kg bw. Additionally, a supporting study on rats exposed to the test substance via the oral route (Carpenter et al., 1974) revealed an LD50 of 1230 mg/kg bw (the original value was reported as 1540 µL/kg).

 

Acute toxicity: Inhalation

In a study similar to OECD TG 403 (BASF, 1980), acute toxicity via inhalation was tested based on a dynamic inhalation system at which the whole-body was exposed with an analytical and nominal determination of concentration. Ten Sprague Dawley rats (male / female) were exposed to vapour with the test item for 4 hours. The analytical concentrations determined at 0.60, 1.54, 1.86, 2.64, 5.95 mg/L while the nominal concentrations used were 1.60, 4.02, 5.35, 8.03, 9.64 mg/L. After the exposure period, the surviving animals were observed for 14 days. The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. The absolute body weight gain and the relative body weight gain (difference in weight between the initial weight of the animals and the following weights) were determined from the values and presented graphically. Clinical findings and lethality were recorded daily. At the end of the 14-day observation period, the animals were sacrificed with CO2 and were subjected to a gross-pathological examination like all other animals which had died before. At the dose of 0.6 (1.6) mg/L and 1.54 (4.02) mg/L: no deaths were observed. At the concentration of 1.86 (5.35) mg/L, 5/10 male and 5/10 females dead animals were found. At the dose of 2.64 (8.03) mg/L: 7/10 male / 8/10 females dead animals were found. At the dose of 9.64 (5.95) mg/L all animals died. In all dose groups the following clinical signs were observed: watery eye/nasal secretion (partly reddish), eyelid closure, salivation, intermittent breathing, crouching position, abdominal position, twitching, trembling resp. clonic convulsions, apathy, staggering gait, ruffled fur. The gross pathology revealed acute dilatation of the atrium in heart; acute congestive hyperemia; intense blood filling with slight edematization in the lung; broadened liver, loam-brown liver lobe periphery, partly liver with lateral corrugation in the animals that died. The animals that were sacrificed, nothing abnormal was detected. All symptoms were weaker in the lower dose groups. The LC50 was determined to be 2.1 mg/L air (2100 mg / m3). Further, the test substance was tested on male/female rats which were exposed on the test substance using vapours for 3 and 10 minutes (BASF, 1976). For saturation, air was passed through an approximately 5 cm high layer of the test substance. 12 animals per sex and per dose were used when the exposure period was 3 minutes and 6 animals per sex and per dose when the exposure period was 10 minutes. When the animals were exposed for 3 minutes, no deaths were observed. When the animals were exposed for 10 minutes, 6/6 animals were found dead. In gross pathology examinations, the following effects were observed: acute heart dilatation (both-sided); acute congestive hyperemia; lung: partly infarctoid blood filling with slight edematization. Additionally, a supporting study on rats exposed to the test substance via inhalation (Carpenter et al., 1974) resulted in 6/6 deaths after 20 minutes of exposure to the test substance in a room saturated or enriched at room temperature. During the same study, after 4 h exposure to a concentration of 1000 ppm (4.6 mg/L), 2 out of 6 animals were found dead.

 

Acute toxicity: dermal  

In a study on rabbits exposed to the test substance via the dermal route (Carpenter et al., 1974) the LD50 was determined at 460 mg/kg bw. The information with regard to the lethal dose was reported as LD50 = 570 µL/kg in the same. The description of materials and methods is brief, however the reported LD50 value for the acute toxicity via the dermal route, taking into account the available information for acute toxicity via the oral route and inhalation, suffice for classification of the test substance.

Justification for classification or non-classification

Based on an oral LD50 of 472 mg/kg bw, a dermal LD50 of 460 mg/kg bw, and an inhalation LC50 of 2100 mg / m3, the substance is classified as Acute Tox. 4 H302: Harmful if swallowed, Acute Tox. 3 H331: Toxic if inhaled, Acute Tox. 3 H311: Toxic in contact with skin, in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.