2-methylbutan-2-ol

Endpoint summary

Description of key information

The acute oral LD50 value of 2-Methylbutan-2-ol derived from the key study in rats was 5184 mg/kg bw. 
The acute inhalation LC50 value in rats derived was between 20.6 mg/L and 10.8 mg/L. 
The acute dermal LD50 value of 2-Methylbutan-2-ol was 1720 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

Study period:

1968-09-20 to 1968-09-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study predating guidelines and GLP, but meeting the principles of OECD TG 401.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: "US-rats"

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 142 - 240 g (males); 120 - 174 g (females)

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: From: 1968-09-20 To: 1968-10-07

Route of administration:

oral: gavage

Vehicle:

other: aqueous tragacanth emulsion

Details on oral exposure:

VEHICLE
- Vehicle concentration: 30% (6400, 3200 mm³/kg bw) , 20% (1600 mm³/kg bw), 2% (200 mm³/kg bw)

Doses:

6400, 3200, 1600 or 200 mm³/kg bw

No. of animals per sex per dose:

10 males and 10 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight taken at study start only for dose determination, but not reported
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs monitored but frequency unknown, gross necropsy on fatalities

Statistics:

not performed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 400 other: mm³/kg bw

Based on:

test mat.

Remarks on result:

other: 5184 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

> 6 400 other: mm³/kg bw

Based on:

test mat.

Remarks on result:

other: > 5184 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 5 000 other: mm³/kg bw

Based on:

test mat.

Remarks on result:

other: 4050 mg/kg bw

Mortality:

Totals after 14-days:
6400 mm³/kg bw: 10/20
3200 mm³/kg bw: 1/20
1600 mm³/kg bw: 0/20
200 mm³/kg bw: 0/20

Males:
6400 mm³/kg bw: 2/10 (1/10 within 1 h, 2/10 within 24 h)
3200 mm³/kg bw: 1/10 (0/10 within 1 h, 1/10 within 24 h)
1600 mm³/kg bw: 0/10
200 mm³/kg bw: 0/10

Females:
6400 mm³/kg bw: 8/10 (7/10 within 1 h, 8/10 within 24 h)
3200 mm³/kg bw: 0/10
1600 mm³/kg bw: 0/10
200 mm³/kg bw: 0/10

Clinical signs:

other: 3200 and 6400 mm³/kg bw Immediately after application: prone or lateral position, irregular respiration, narcosis; 1 day: panting, ruffled fur; 2 days: fully recovered 1600 mm³/kg bw Immediately after application: dyspnoea, watery secretion from snout, wa

Gross pathology:

Organs: no abnormalities detected
Perished animals: sepsis

Other findings:

none

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 184 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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only secondary literature

Principles of method if other than guideline:

Acute inhalation toxicity, no further details

GLP compliance:

not specified

Test type:

other: standard acute method (in vivo)

Limit test:

no

Species:

rat

Duration of exposure:

6 h

Concentrations:

Nominal concentrations: 15800; 5700; 3000 amd 1100 ppm (57; 20.6; 10.8; 4 mg/L)

No. of animals per sex per dose:

4 rats

Sex:

not specified

Dose descriptor:

LC100

Effect level:

5 700 ppm

Exp. duration:

6 h

Remarks on result:

other: 20.6 mg/L

Sex:

not specified

Dose descriptor:

LC50

Effect level:

3 000 - 5 700 ppm

Exp. duration:

6 h

Remarks on result:

other: between 20.6 and 10.8 mg/L

15800 ppm (57 mg/L) : At the top level, all animals exhibited motor incoordination within 90 min. and all were dead within 3 hours.5700 ppm (20.6 mg/L): Those exposed to 5700 ppm were unconscious at the end of exposure and died within 24 hours. Deaths were believed to be due to respiratory failure.3000 ppm (10.8 mg/L): The rats exposed to 3000 ppm were als unconscious at the end of the exposure, lost weight for a few days and then recovered and survived.1100 ppm (4 mg/L): Those exposed to 1100 ppm exhibited slight motor inccordination at the end of the exposure, appeared normal 24 hours later, experienced no weight loss and survived.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

20.6 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 720 mg/kg bw

Additional information

Acute oral toxicity

In an acute oral toxicity key study (BASF AG, 1968), rats (10/sex) were given a single oral dose of 2 -Methylbutan-2 -ol in aqueous tragacanth emulsion at doses of 6400, 3200, 1600 or 200 mm3/kg bw (5184, 2592, 1296 or 162 mg/kg bw). Animals were then observed for up to 14 days. The following treatment related clinical signs were noted: prone or lateral position, irregular respiration, narcosis, panting, ruffled fur, dyspnoea, watery secretion from snout, waddling gait, chewing, hyperactivity, increased respiratoty rate. The oral LD50 was determined to be 5184 mg/kg bw in male and female rats combined.

Munch (1972) reported an oral LD50 of 2027 mg/kg bw for the rabbit. Rowe and MCCollister (1982) and Schaffarzick et al., 1952 reported an oral LD50 of 1000 -2000 mg/kg bw and 1000 mg/kg bw for the rat. As no further info on study methodology is available and the results of the scienfifically fully reliable and well documented key study (BASF, 1968) revealed a much higher oral rat LD50, the results reported by Rowe and McCollister (1982) and Schaffarziek et al., (1952) are disregarded.

Acute inhalation toxicity

In an acute inhalation toxicity study (Rowe and McCollister, 1982) groups of 4 rats each were exposed for 6 hours to nominal concentrations of 15800; 5700; 3000 and 1100 ppm (57; 20.6;10.8; 4 mg/L). At the top level, all animals exhibited motor incoordination within 90 min and all were dead within 3 hours. Those exposed to 5700 ppm were unconscious at the end of exposure and died within 24 hours. All other groups survived. The LC100 was 20.6 mg/L and the LC50 was between 20.6 and 10.8 mg/L.

In a second acute inhalation toxicity study (BASF AG, 1968), young adult rats (12 females) were exposed by inhalation route to an enriched atmosphere of 2-Methylbutan-2-ol for 8 hours. In a vapour generating system 200l/air was bubbled through the substance column of about 5 cm above a fritted glass dics in a class cylinder. At 20°C the nominal concentration was 14.02 mg/L. At a temperature of 110°C foam was generated and a foam inhibitor was added. As a result no detailed concentration value could be stated at 110°C. Animals then were observed for 7 days. No mortality was observed. Smeared snouts were detected as clinical signs and at gross pathology chronic bronchitis at two animals could be seen at 110°C. The LC50 for female rats was > 14.02 mg/L (20°C). This result is in line with the acute inhalation toxicity study of Rowe and McCollister, 1982). 

Acute dermal toxicity

In the only available acute dermal toxicity study (Rowe and McCollister, 1982) rabbits were exposed with 2-Methylbutan-2-ol by occlusive application to the intact belly skin for 24 h. The LD50 value was 1720 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Most reliable study

Justification for selection of acute toxicity – inhalation endpoint
Most reliable study

Justification for selection of acute toxicity – dermal endpoint
Most reliable study

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, 2 -Methylbutan-2 -ol is not subject to classification.

Based on the results of the acute inhalation toxicity studies 2 -Methylbutan-2 -ol is subject to classification with R20 (harmful by inhalation) according to Directive 67/548/EEC (DSD) and category 4, H332 (harmful if inhaled) according to Regulation (EC) No 1272/2008 (CLP/GHS).

Based on the results of the acute dermal toxicity study 2 -Methylbutan-2 -ol is subject to classification with R21 (harmful in contact with skin) according to Directive 67/548/EEC (DSD) and category 4, H312 (harmful in contact with skin) according to Regulation (EC) No 1272/2008 (CLP/GHS).

According to Regulation (EC) No 1272/2008, 2 -Methylbutan-2 -ol is classified as STOT SE 3, H336 and H335, respectively.