Registration Dossier

Administrative data

Description of key information

Acute toxicity:
- oral: LD50 = 1420 mg/kg bw
- inhalative: LC50 > 21.3 mg/l/4 h
- dermal: LD0 = 172 mg/kg bw

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: Comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Internal methods which were in large part similar to the methods described in OECD Guideline 401
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: mean 242 g (male), 185 g( female)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2, 16, 20%
- Amount of vehicle (if gavage): 10 ml/kg bw
Doses:
0.2, 1.25, 1.6, 2.00 ml/kg bw (= ca. 172, 1076, 1377, 1722 mg/kg bw)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1.65 mL/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 420 mg/kg bw
Mortality:
2.000 ml/kg bw: 8/10 within 48 h; 10/10 within 7 days
1.60 ml/kg bw: 4/10 within 24 h
1.25 ml/kgbw : 1/10 within 24 h
0.20 ml/kg bw: 0/10 within 7 days
Clinical signs:
1.60 -2.00 ml/kg bw:
- shortly after application: staggering, apathy, dyspnea, abdominal and lateral position,
- after 10 -30 minutes: narcosis
- after 5 h: narcosis, discharge of the eyes
- 48 h: abdominal and lateral position, narcosis
- days 3-4: intermittent respiration, apathy, piloerection, red crusted eyes
- days 5-6: no effects

1.25 ml/kg bw:
- shortly after application: staggering, apathy, dyspnea, abdominal and lateral position,
- after 10 -30 minutes: temporal narcosis
- after 5 h: narcosis, discharge of the eyes
- up to 48 h: intermittent respiration, apathy, piloerection, red crusted eyes
- after 6 days: no effects

0.20 ml/kg bw:
- up to 24 h: abdominal and lateral position, apathy
- later no effects
Gross pathology:
- 3x hydrothorax, collapse of lung, blood in renal capsule, blood in urine at 2.0 ml/kg bw
- organs: no effects
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Dose descriptor:
LD50
1 420 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:
04.05.1988 - 18.05.1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD)
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr . K . Thomae GmbH, 7950 Biberach
- Age at study initiation: ca. 8 - 9 weeks
- Weight at study initiation: male 259 +/- 6.4 g (average), female 185 +/- 6.5 g (average)
- Identification: colormark on tail
- Housing: 5 per cage, Type D III, Firma Becker
- Diet (e.g. ad libitum): ad libitum, KLIBA Labordiät Ratte/Maus, 24-343-4 10 mm Pellet, Klingentalmühle AG, CH-4303 Kaiseraugst
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: steel cage placed in Inhalation chamber made of glass and steel
- Exposure chamber volume: ca. 200l
- Method of holding animals in test chamber: single housing
- Source and rate of air: 3000 l/h, central air conditioning system
- System of generating particulates/aerosols: dosing-pump (DESAGA) and glass-vapourizer attached to air-conditioning system
- Temperature, humidity, pressure in air chamber: 20 - 24 °C, 30 - 70% humidity


TEST ATMOSPHERE
- Brief description of analytical method used: Two beakers connected to a fritted glass beaker filled with the solvent 2-propanol.
- Samples taken from breathing zone: yes, once per hour sample, analyzed by gas chromatography with a GC HP 5840A (Hewlett Packard)
Analytical verification of test atmosphere concentrations:
yes
Remarks:
by gas chromatography and substance weight loss during exposure
Duration of exposure:
4 h
Concentrations:
21.3 mg/l
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 and weighing: prior to begin of study, after 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality
Statistics:
statistic was calculated acc. binominal model
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21.3 mg/L air
Exp. duration:
4 h
Mortality:
no deaths occured
Clinical signs:
- During exposition: accelerated and intermittent respiration, narcotic-like condition, lateral position, anemic pallor
- until day 8: Abdominal or lateral position, narcotic-like condition, accelerated to intermittent respiration, reduced general state, apathy, ataxia, piloerection, red crusted eyelid, anogenital region smeared with urine
- from day 9: no clinical signs
Body weight:
Body weight gain was delayed in the first week compared to historical control, but equals in the second week.
- average weight prior to begin of study: male 259 g, femal 185 g
- average weight after 7 days: 275 g, 198 g
- average weight after 14 days: 315 g, 208 g
Gross pathology:
no findings
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Dose descriptor:
LC50
21 300 mg/m³

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: Comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
internal BASF method was used, which was in large part equivalent to OECD Guideline 402
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
Vienna White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.83, 2.84, 2.77 kg
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2 ml/kg bw
- Concentration (if solution): 100%
Duration of exposure:
24 h
Doses:
100%
No. of animals per sex per dose:
3 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 9 days
- Frequency of observations and weighing: prior to begin and at the end of study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Sex:
male
Dose descriptor:
LD0
Effect level:
0.2 mL/kg bw
Sex:
male
Dose descriptor:
LD0
Effect level:
ca. 172 mg/kg bw
Mortality:
no deaths occured
Clinical signs:
no effects observed
Body weight:
no effects
Gross pathology:
no effects
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
172 mg/kg bw

Additional information

Acute oral toxicity of 2-methylbut-3-yn-2-ol was assessed in a study, which was in large part equivalent to OECD guideline 401 (BASF, 1966). Ten male and female rats per sex and dose were oral administered with concentrations of 0.2, 1.25, 1.6 and 2.00 ml/kg bw, corresponding to ca. 172, 1076, 1377 and 1722 mg/kg bw, respectively. Beside clinical signs including dyspnea and narcosis also mortality was noted, so that a LD50 of 1.65 ml or 1420 mg/kg was calculated.

In two other studies without further details LD50 values of 1950 mg/kg bw and a range of 1300-2600 mg/ kg bw in rats were reported (Brown, 1995; Air Products, 1975). A LD50 of 500 mg/kg bw for mice was found in a Russian study, while this value was reported to be 1800 mg/kg bw in another earlier study, respectively (Balynina, 1987; Keil, 1954).

The acute inhalative toxicity of 2-methylbut-3-yn-2-ol was analyzed in an inhalation study performed according OECD guideline 403 (BASF, 1988). In this study, five rats were exposed for four hour to saturated atmosphere corresponding to a vapor of 21.3 mg/l. Although local irritation and narcosis were noted during exposure, no mortality occurred during the 14 day observation period, so that the LC50 was > 21.3 mg/l.

In another study which was in large part equivalent to OECD guideline 403, up to twelve rats were exposed to a vapor of 67.5 mg/l for 30 minutes inhalation, 62.93 mg/l for 1h inhalation and 61.5 mg/l for 4 h inhalation, respectively (BASF; 1966). As result, severe irritation to eyes and mucosa and narcosis was noted, but exposure was not lethal during the first 30 minutes of exposure. However, all animals died within the 4 hours exposure period.

In a Russian study, the LC50 found in mice was reported to be 2 mg/l air after two hours with no further details given (Balynina, 1987). In another study which was only available as secondary literature, the LC50 after 1-hour exposure in rats was > 20 mg/l (Air Products, 1975).

In an early study a cat, a rat, a Guinea pig and a rabbit were exposed to concentrations of 5 mg/l  for one hour, 10 mg/l for three hours and 17 mg/l for three and eight hours, respectively (I.G. W.-Elberfeld, 1940). As result, a LC0 of 17 mg/l was found for the rabbits, whereas the same value was the LC100 for the cat, the Guinea pig and the rat when exposed for 8 hours, respectively.

Acute dermal toxicity was observed in a study which was in large part equivalent to methods described in OECD guideline 402 (BASF, 1966). Three male Vienna White rabbits received a dermal application of 0.2 ml pure 2-methylbut-3-yn-2-ol to the shaven flank for 24 hours. Since no mortality was noted, the LD0 was 0.2 ml/kg bw corresponding to ca. 172 mg/kg bw.

In another study performed according to OECD guideline 402, a LD50 of >2000 mg/kg bw was estimated for dermal acute toxicity in rats (Air Products, 1975).

The intraperitoneal LD50 in mice was found to be 1200 mg/kg bw (BASF, 1966), and 3600 mg/kg bw in another study, which was only available as secondary literature (OECD SIDS, 2002). In two other studies, the subcutaneous LD50 in this species was 1161 and 2340 mg/kg bw, respectively (Soehring, 1955; Kitagawa, 1956).

Justification for classification or non-classification

Due to the observed LD50 of 1420 mg/kg bw a classification for acute oral toxicity is required. However, no classification is necessary with respect to inhalation and dermal exposure, although high vapor concentrations can cause a narcotic effect as also seen after oral ingestion.

Due to the (reversible) narcotic effects observed after oral exposure and inhalation, the test substance has to be classified as STOT SE category 3, H336 "May cause drowsiness or dizziness.." according to Regulation 1272/2008 (CLP).