But-3-yn-2-ol

Endpoint summary

Description of key information

An acute oral LD50 for rats was established to be 45 mg/kg bw.
The LD50 for acute inhalation toxicity in rats was determined to be > 0.53 mg/L and < 2.09 mg/L. 
For acute dermal toxicity the LD50 range was established to be > 69 to < 172 mg/kg bw  in rabbits. 

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:

September 1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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

Species:

rat

Strain:

other: not specified

Sex:

female

Details on test animals or test system and environmental conditions:

No further details provided

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

50, 10, 2% test substance were administered.

Doses:

10, 20, 40, 50, 63, 79, 100, 126, 500 and 5000 mm3/kg bw (= 0.01 - 5 ml/kg bw)
= 9, 17, 34, 43, 54, 68, 86, 109, 431, 4308 mg/kg bw (Density: 0.8616 g/ml @20°C [CRC, 2008])

No. of animals per sex per dose:

For 5000, 500 and 10 mm3/kg one animal was tested. For the other concentrations (20-126 mm3/kg bw) 5 animals were tested. The sex distribution was not specified.

Control animals:

no

Details on study design:

No further details were provided.

Statistics:

No data provided

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 45 mg/kg bw

Based on:

test mat.

Remarks on result:

other: original value: ca. 52.6 mm3/kg, mg/kg bw calculated based on density at 20 °C = 0.8616 g/mL (CRC 2008)

Mortality:

See table below.

Clinical signs:

Trembling, apathy, bristled fur, partly lateral position and seizures were observed.
From the animals that died due to treatment, most died within a few hours. Some died one day after administration of the test substance.

Body weight:

No data was provided.

Gross pathology:

No data was provided.

mm3/kg bw	mg/kg bw	dead/ total animals
10	9	0/1
20	17	0/5
40	34	2/5
50	43	4/5
63	54	4/5
79	68	4/5
100	86	4/5
126	109	5/5
500	431	1/1
5000	4308	1/1

LD50 (rat, oral) = 52.6 mm3/kg bw = 45.3 mg/kg bw

Interpretation of results:

Category 2 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

45 mg/kg bw

Quality of whole database:

Similar to guideline study and non GLP study. The lowest LD50 value.

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:

1988-06-08 to 1988-06-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

- Color: yellow
- Form: liquid
- Storage: at room temperature

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, 7950 Biberach, Germany
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: males 260 +/- 8.3 g; females 189 +/- 8.0 g
- Housing: 5 animals per cage; wire cages, type DIII (Company Becker); no bedding
- Diet: ad libitum; KLIBA laboratory diet rat/mouse A 343 10-mm pellets (Klingentalmuehle AG, Kaiseraugst, Switzerland)
- Water: ad libitum; tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): AC controlled
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole-body inhalation system
- Exposure chamber volume: V = 200 L
- Method of holding animals in test chamber: single; in wire cages which were located in a glass-steel inhalation chamber
- Source and rate of air: air was supplied by central AC; Volume of air was 3000 L/h
- Method of conditioning air: central air conditioning
- System of generating particulates/aerosols: continuous infusion pump INFU 362 (INDIGEL/Switzerland) and a glass evaporator with thermostat
- Temperature, humidity, pressure in air chamber: temp: 19-25°C in the exposure apparatus; underpressure was adjusted to 100 L/h in the treatment chamber

TEST ATMOSPHERE
- Brief description of analytical method used: once per hour samples were taken (one per treatment group); the vapour was collected into Propanol-2; Analysis was done with a gas chromatograph (GC HP 584ß A, Hewlett Packard)
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle: air
- Concentration of test material in vehicle: Concentration was determined through substance use and air volume used; and in samples via mass determination and sample volume (mg/L)

CLASS METHOD
- Rationale for the selection of the starting concentration: The concentration 3.33 mg/L was selected on the basis of the information available on the toxicity of the test substance. The remaining concentrations were selected in such a way that it was possible to determine an LC50.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.53, 2.09, 3.33 mg/L (nominal)

No. of animals per sex per dose:

5

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. Clinical findings were generally recorded several times during exposure and at least once each workday during the post-exposure observation period. A check for mortalities was made daily.
At the end of the 14-day observation period, the surviving animals were sacrificed with CO2 and were subjected to a gross-pathological examination like all other animals which had died before.

Statistics:

Statistical analysis of concentration-effect ratio was done with FORTRAN-programm AKPROZ.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.53 - < 2.09 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.53 mg/L: no deaths; 2.09 and 3.33 mg/L: 10/10

Clinical signs:

other: During exposure: irregular, delayed up to lengthy breathing, paleness of ear and extremities, severe apathy, abdominal position, crouch position, ruffled fur, watery nasal secretion, salivation, lachrymation After exposure: lengthy and delayed breathing,

Body weight:

Body weight development was recorded for the surviving animals (0.53 mg/L). Females showed no differences to historical controls. Males had a shlight delay during the 2. week of observation.

Gross pathology:

Animals that died: acute congestive hyperemia; lung: acute emphysema - moderate (9 x)
Sacrificed animals: organs: nothing abnormal detected

Other findings:

No other findings were observed.

Interpretation of results:

Category 2 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

530 mg/m³

Quality of whole database:

The key study was well-documented and conducted similar to OECD 403.

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

Study period:

April 1957

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:

yes

Remarks:

lower animal number/group, only 2 doses tested

Principles of method if other than guideline:

according to Hill ("The manufacturing chemist's Ass. Program for the labeling of hazardouos chemicals"; Ass. Food. and Drug Off. 18, 142, 1954).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

The pure substance and a solution of 40% were tested.

Species:

rabbit

Strain:

Vienna White

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data provided

Type of coverage:

occlusive

Vehicle:

other: water and unchanged

Details on dermal exposure:

TEST SITE
- Area of exposure: back skin, shaved, 50 cm2
- Type of wrap if used: lamination

REMOVAL OF TEST SUBSTANCE
Test substance was removed by removing the wrap.

TEST MATERIAL
- Amount(s) applied: 200 mm3/kg (pure) and 80mm3/kg (40 %)
- Concentration: pure and 40 % in water
- Constant volume or concentration used: yes

VEHICLE
For 40 % test substance was mixed with water.

Duration of exposure:

24 hours

Doses:

80 and 200 mm3/kg
69 and 172 mg/kg bw (calculated based on density at 20 °C = 0.8616 g/ml, CRC 2008)

No. of animals per sex per dose:

3 animals per dose but no sex distribution provided

Control animals:

no

Details on study design:

- Duration of observation period following administration: 4 weeks
- Frequency of observations and weighing: every 1 - 3 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

No statistical analysis was performed.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 69 - < 172 mg/kg bw

Based on:

test mat.

Remarks on result:

other: original range: > 80 to < 200 mm3/kg bw , mg/kg bw calculated based on density at 20 °C = 0.8616 g/ml

Mortality:

All animals treated with the pure test substance (200 mm3/kg bw) died within 8 - 24 hours after application.
All animals treated with the 40 % test substance (80 mm3/kg bw) survived the application.

Clinical signs:

Animals treated with the pure test substance developed apathy and diarrhea before death.
Animals treated with the 40 % test substance were atonic and apathetic but recovered within 24 h.

Body weight:

Survivors showed no weight loss.

Gross pathology:

Increased fluid accumulation in the thoracic region, liver and kidneys enrichment with blood was detected in animals treated with the pure test substance.

Interpretation of results:

Category 2 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

69 mg/kg bw

Quality of whole database:

Basic information given in a similar to guideline but non GLP study.

Additional information

Acute toxicity: oral

Key study

The key study for oral toxicity was performed in rats (VII/97-98, 1958). Rats orally received the test substance in different concentrations. No mortality was detected in the lower doses (10 and 20 mm3/kg bw = 9 and 17 mg/kg bw). For higher doses most animals died (40 - 5000 mm3/kg bw = 34 - 4308 mg/kg bw) within a few hours or up to one day after administration. The LD50 was established at 45 mg/kg bw respectively 52.6 mm3/kg bw.

Supporting studies

Supporting results were obtained from other oral studies in rats, rabbits and cats (VII/97, 1958; XVII/112, 1967).

Wang and Bai (1998) developed a QSAR model to predict acute oral toxicity in mammals based on structure-activity relationships. The measured LD50 in mouse for the test substance was 30 mg/kg bw. It was concluded that the predicted and observed results mostly matched and the model may be used in general to classify and predict the toxicity of alcohols on rats and mice.

Koleva et al. (2011) developed a QSAR model to predict acute oral toxicity in mammals. The measured logLD50-1 in mouse for the test substance was 0.37 mmol/kg bw. The predicted logLD50-1 was -1.84 mmol/kg bw. It was concluded that the lack of accurate and reliable toxicity data, together with the many different biological and molecular events, make the in sillico prediction of LD50 difficult.

 

Acute toxicity: inhalation

Key study

The key study (1310753/877089, 1988) for acute inhalation toxicity was conducted similar to OECD 403. Rats were exposed to a vapor containing the test substance and air. The concentrations of the test substance were 0.53, 2.09 and 3.33 mg/L. With 2.09 and 3.33 mg/L animals died on the exposure day. Animals exposed to 0.53 mg/L survived and showed no remaining symptoms starting at day 1 after exposure. The LD50 was determined to be > 0.53 mg/L and < 2.09 mg/L.

Supporting studies

In a supporting studies (inhalation risk test), rats were treated with vapor of the test substance in different concentrations and durations (XVII/112, 1967). From animals exposed for 3 min 1 out of 12 died. Exposures of 10 min up to 3 h led to the death of all animals within few hours. Directly after/during treatment animals developed severe mucosal irritation, staggering, apathy and pain reflexes were lowered. Pathology revealed excessive liquid accumulation in the skin, ascites and atonic intestine. From the surviving animals 2 were found to have developed chronic bronchitis.

In a second supporting study (IRT), rats were exposed to the test substance via inhalation (VII/97-98, 1958). For vapor production pure and 40 % substance were used and the exposure time was 4, 8 and 15 min. Animals developed various clinical symptoms and for higher exposure time most/ all animals died while after the lower exposure time most animals recovered after 2 days. Pathology revealed fluid accumulation in the region of the costal pleura in animals deceased during or following the exposure. The test substance was concluded to be highly toxic due to the observations.

 

Acute toxicity: dermal

Key study

Rabbits were exposed to the test substance on the back skin (VII/97-98, 1958). An application of 172 mg/kg bw of the pure test substance led to the deaths of the animals within 24 hours. Application of the same amount of 40 % test substance in water (ca. 69 mg/kg bw) did not cause death in the animals, only indisposition at the beginning and animals recovered within 24 h after treatment. It was concluded that the test substance is absorbed rapidly into the skin. The LD50 range was established to be > 69 to < 172 mg/kg bw.

 

Other routes:

The test substance was also administerd to mice, rabbits and cats by i.p., i.v. or s.c. inhection (XVII/112, 1967, VII97 -98, 1958) demonstrating the high acute toxicity of the substance.

Justification for classification or non-classification

Acute oral toxicity

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute oral toxicity in Category 2. H300: Fatal if swallowed.

 

Acute inhalation toxicity

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute inhalation toxicity in Category 2. H330: Fatal if inhaled.

 

Acute dermal toxicity

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute dermal toxicity in Category 2. H310: Fatal in contact with skin.