2-piperazin-1-ylethanol

Endpoint summary

Description of key information

oral: LD50 ca. 4244 mg/kg bw (rat)

inhalation: no mortality/clinical signs observed (rat)

intraperitoneal: LD50 < 678 mg/kg bw (mice)

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:

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:

yes

Remarks:

(weight variations in animals exceed 20% of the mean weight, observation period of 7 days, no details on animal husbandry)

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
- Age at study initiation: young adult laboratory rats
- Weight at study initiation: 100 - 224 g

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(doubly distilled)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10-20 mL/kg bw
The doses were administered as aqueous solutions of 8% (800 cm³/kg), 20% (1600 cm³/kg) and 30% (3200, 4000 and 5000 cm³/kg) test substance.

Doses:

800, 1600, 3200, 4000 and 5000 cm³/kg (849, 1698, 3396, 4244, 5305 mg/kg bw - conversation in mg/kg is based on the density: d= 1.06 g/cm³)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Frequency of weighing: prior the start of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 4 244 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Corresponds to 4000 cm³/kg; the mg/kg was calculated on the density d: d= 1.061 g/cm³. 1 male/3 females died within the first 24 h post exposure in this dose group.

Mortality:

5305 mg/kg: All females died within the first 24 h and 3 males died within 48 h.
4244 mg/kg: 1 male and 3 females died within the first 24 h.
3396 mg/kg: 1 male and 2 females died within the first 24 h.
1698 mg/kg:1 animal died within 7 days.

Clinical signs:

other: 5305 and 4244 mg/kg: high stepping gait, motor excitation, intermittent respiration, abdominal position and paresis (hindlimb), immediately after application; piloerection, nose and eyes with reddish crusts, intermittent respiration, apathy and squatting

Gross pathology:

Animals that died:
5305 mg/kg: smeared fur (snout and anogenital region), dilatation of the stomach and intestine (partly filled with blood and liquid content).
4244 mg/kg: smeared fur (snout); dilatation of the stomach and intestine (partly filled with blood and liquid content).
3396 mg/kg: smeared fur (snout and anogenital region), diarrhea.
Animals examined at termination of the study: Organs without particular findings.

Mortality:

Dose (mg/kg)	Conc.(%)	dead within 1h	dead within 1 day	dead within 2 days	dead within 7 days
5305	30	0/10	6/10	8/10	8/10
4244	30	1/10	4/10	4/10	4/10
3396	30	0/10	3/10	3/10	3/10
1698	20	0/10	0/10	0/10	1/10
849	8	0/10	0/10	0/10	0/10

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 244 mg/kg bw

Quality of whole database:

equivalent to OECD TG 401

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

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)

Version / remarks:

(adopted on 1981, 12th may; inhalation hazard test)

Deviations:

yes

Remarks:

(animals were observed for only 8 days, only 3 animals for each exposure time were used, no details only animal husbandry, exposure period of 8 hours, concentration of test substance in air mixture was not determined)

GLP compliance:

no

Test type:

other: inhalation hazard test (IHT)

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 172 g (mean)

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

The test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of the test substance at the temperature chosen for vapor generation (20 °C). 6 rats per sex were exposed to the vapors, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8h. The documentation of clinical signs was performed over a period of 8 days. In order to verify the results, the test was repeated once with new groups of animals.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

In the study report and the raw data no substance loss but an increase in substance weight was recorded.

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

discriminating conc.

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occured.

Clinical signs:

other: No clinical signs observed.

Body weight:

The treated animals gained weight (mean weight at study end: 199 g).

Gross pathology:

In one animal, chronic bronchitis and bronchiectasis in the right superior lobe of the lung were observed. Other animals were negative.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

equivalent to OECD TG 403

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

oral

Acute oral toxicity was determined in a study equivalent to OECD TG 401. The test item was administered to young laboratory rats (strain not specified) by gavage in doses of 849, 1698, 3396, 4244 and 5305 mg/kg bw (5 animals per dose/sex). The application volume was 10 to 20 mL/kg bw. Doubly distilled water was used as vehicle. Prior start of the study, rats was weighted and the doses were administered in aqueous solutions. Necropsy of survivors was performed and clinical signs were recorded after an observation period of 7 days.

At the highest dose level, all female animals died within 24 h and 3 male animals died within 48 h. At 4244 mg/kg bw one male and 3 female animals died within the first 24 hours. At these dose levels, high stepping gaint, motor excitation, intermitted respiration, piloeration, apathy and squatting posture until including days 3 were recorded. In addition, nose and eyes showed reddish crusts. No clinical signs and findings were observed in the surviving animals from the fifth day onward.

At 3396 mg/kg bw one male and two female animals died within the first 24 hours and at 1698 mg/kg bw one animal died within 7 days. At these doses, clinical signs of irregular respiration and squatting posture from hour 2 until hour 4 after application occurred. No clinical findings were observed in surviving animals from the fifth observation day onward.

Animals examined at termination of the study showed no particular organs findings. Animals which died during the study had smeared fur, dilatation of the stomach and the intestine was partly filled with blood and liquid (5306 mg/kg bw and 4244 mg/kg bw).

The LD50 was ca. 4244 mg/kg bw for male and female animals (BASF, 1968).

inhalation

An inhalation hazard test equivalent to OECD TG 403 (1981) was performed to assess the acute inhalation toxicity. Male and female rats (strain not specified) were exposed to vapors of the test substance in air mixture (concentration not determined) for a period of 8 hours. The test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of the test substance at the temperature chosen for vapor generation (20 °C). 6 rats per sex were exposed to the vapors. The documentation of clinical signs was performed over a period of 8 days. In order to verify the results, the test was repeated once with new groups of animals. Necropsy of all animals was performed. No mortality occurred and no clinical signs were observed. The treated animals gained weight. Only one animal showed chronic bronchitis and bronchiectasis in the right lobe of the lung. No LD50 was determined (BASF AG, 1967).

intraperitoneal

In a standardized BASF study, the acute toxicity of the test item after single intraperitoneal administration was assessed. Doses of 212, 424, 678, 848 mg/kg bw of the test substance were administered to mice, while 5 animals per dose were utilized. The duration of observation was 7 days. Immediately after application, labored respiration, aqueous secretion from the oral cavity, shrunken flanks, high stepping gait, indicated morphine tails, abdominal position and closed eyes were observed. During the following days, the surviving animals showed clotted eyes, scrubby fur, accelerated respiration. 5 to 6 days after exposure, no clinical signs were observed. At the highest dose level all animals died within 48 h. At 678 mg/kg bw all female and 2 male animals died within 48 hours post application. At 424 mg/kg bw one male and one female died within the 7 day observation period. Animals that died during the study showed livers with bloody pigmentation and intestine filled with bloody fluids. Animals examined at termination of the study showed connation of liver and stomach. The LD50 for male and female mice after i.p. application was < 678 mg/kg bw (BASF, 1968).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The oral LD50 was ca. 4244 mg/kg bw. As a result the substance is not classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179. An inhalation study with an atmosphere saturated with vapors of the test item revealed no adverse effects and therefore no classification for acute inhalation toxicity is warranted.