Butan-1-ol

Endpoint summary

Description of key information

oral, LD50
rat ca. 2290 mg/kg bw (similar OECD TG 401; Union Carbide Corporation 1967)

rat 2510 mg/kg/ bw (Jenner 1964)

rat 4360 mg/kg/bw female (Union Carbide Corporation 1951)

mouse 2680 mg/kg bw (Rumyanstev et al., 1979, Val. 4)
rabbits 3500 mg/kg bw (Munch, 1972; Munch and Schwarze, 1925, Val. 4)
Golden hamsters 1200 mg/kg bw (Dubina and Maksimov, 1976, Val. 4)
Dogs, Minimum lethal dose: 1782 mg/kg bw (Von Oettingen, 1943, Val. 4)

dermal, LD50
rabbits ca. 3430 mg/kg bw (similar OECD 402, Union Carbide Corporation 1951)

inhalation
rats (vapour) LC0 >= 17.76 mg/lL/ 4 h (similar OECD 403; BASF 1979)
rats (vapour) IHT, 21.48 mg/L: no mortality within 7 h (similar OECD 403; BASF 1980)
rats (vapour) LC0 > 24 mg/L/ 4 h; IHT: no mortality within 8 h (similar to OECD 403; Union Carbide Corporation 1951)

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:

1967

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)

Principles of method if other than guideline:

Test material was administered by oral gavage to rats at various dose levels. Survivors were observed for 14 days after dosing.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Harlan Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Dosage levels differ by a factor of 2 in a geometric series.

No. of animals per sex per dose:

Number of female rats used not stated in report but typically 6 rats are used/dose level.

Control animals:

not specified

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 2 292 mg/kg bw

Based on:

test mat.

Remarks on result:

other: converted value (calculated with a density 0.81 g/mL)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2.83 mL/kg bw

Based on:

test mat.

Remarks on result:

other: original value

No additional information available.

Interpretation of results:

Category 5 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 290 mg/kg bw

Quality of whole database:

similar 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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Rats (10 males and 10 females per dose) were exposed for 4 hours to 6.58 or 17.76 mg/l of the test substance. A dynamic inhalation method with whole-body exposure and with analytical and nominal determination of the concentration was used. The animals were observed for 14 days.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Germany
- Weight at study initiation: 185 +- 15 g
- Housing: during exposure: 5 animals/cage
- Diet: ad libitum (food was withdrawn during the exposure)
- Water: ad libitum (water was withdrawn during the exposure)

ENVIRONMENTAL CONDITIONS
no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body inhalation system
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: animals are kept in wire mesh cages within the exposure chamber (5 animals/cage)


TEST ATMOSPHERE
- Brief description of analytical method used: samples were taken from the exposure chamber and analyzed via gaschromatography
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

via gaschromatography

Duration of exposure:

4 h

Concentrations:

6.58, 17.76 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animal weight was determined before the start of the exposure, after 7 days and at the end of the observation period. The animals were checked daily for clinical signs and mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 17.76 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: highest concentration that could be generated

Mortality:

no deaths occured

Clinical signs:

other: none observed

Body weight:

Only marginal differences (slightly reduced weight gain) were observed between the treated groups and the control group. No dose dependency was observed.

Gross pathology:

no abnormalities detected

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

17 760 mg/m³ air

Quality of whole database:

similar OECD TG 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:

7 June - 16 July 1951

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)

Principles of method if other than guideline:

Test material was applied to the shaved skin of New Zealand albino rabbits for 24 hours. Survivors were examined for 14 days after dosing.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

Male albino-New Zealand strain rabbits, 3 to 5 months of age and averaging 2.5 kg in weight were used.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Male albino New Zealand strain rabbits were immobilized during a 24-hour skin contact period. Thereafter, the "Vinylite" sheeting used to retain the dose in contact with the clipped skin of the trunk, was removed and the animals were caged for the remainder of the 14-day observation period.

Duration of exposure:

24-hour

Doses:

1.26, 2.52, 5.0 and 10.0 ml/kg

No. of animals per sex per dose:

4 male/dose

Control animals:

not specified

Details on study design:

Groups of 4 male rabbits were dosed with 1.26, 2.52, 5.0 or 10 ml/kg for a 24 hour period. Survivors were observed for a 14 day observation period following dosing.

Statistics:

Thompson method of calculating the LD50 was used.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 3 430 mg/kg bw

Based on:

test mat.

Remarks on result:

other: converted value (calculated with a density of 0.81 g/mL)

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4.24 mL/kg bw

Based on:

test mat.

95% CL:

3.02 - 5.95

Remarks on result:

other: original value

Mortality:

All rabbits survived following a dose of 1.26 or 2.52 ml/kg. One rabbit survived following a dose of 5.0 ml/kg. All rabbits died following a dose of 10 ml/kg. All deaths occurred on the day of dosing.

Clinical signs:

other: No additional information available.

Gross pathology:

No additional information available.

Other findings:

No additional information available.

No additional information available.

Interpretation of results:

Category 5 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 434 mg/kg bw

Quality of whole database:

similar OECD TG 402

Additional information

Butan-1-ol is slightly acute toxic to experimental animals via the oral and dermal routes of exposure; a low acute toxicity was observed after inhalative exposure.

 

Oral

The most sensitive LD50 value was provided by a study comparable to OECD TG 401 (Union Carbide Corporation 1967). Here, 60 -day-old female Harlan Wistar rats were dosed with butan-1 -ol at various dose levels per gavage. The acute LD50 value was 2.83 mL/kg bw in female rats, corresponding to 2290 mg/kg bw (calculated with a density of 0.81 g/mL). No further data were available.

A comparable LD50 level was observed in a study following the standard acute method with acceptable restrictions (Jenner et al.1967). In this study, 5 young adult Osborne-Mendel rats per sex were dosed with butan-1-ol at different, but unspecified doses. The rats were observed for 14 days and the LD50 values were calculated. After 14 d observation period, the LD50 was 2510 mg/kg bw in rats. Mortality occurred within 4 -18 h after dosing, and depression and coma were reported as clinical signs. Weighing and performance of necropsy was not reported.

In another oral acute study, groups of 10 female rats were orally gavaged with 3160, 3980, 5000 or 6300 mg/kg and observed for 14 days after dosing. Here, 0, 3, 8 and 10 rats died at dose levels of 3160, 3980, 5000 or 6300 mg/kg, respectively.  Deaths following oral doses occurred in many cases within 4 hours and in all but one instance within 24 hours. The LD50 was 4360 mg/kg/bw for female rats (Union Carbide Corporation 1951).

For other common test species oral LD50 values were reported with limited details: 2680 mg/kg bw for mice (Rumyanstev et al., 1979, Val. 4), 3500 mg/kg bw for rabbits (Munch, 1972; Munch and Schwarze, 1925, Val. 4), 1200 mg/kg bw for Golden hamsters (Dubina and Maksimov, 1976, Val. 4), and a minimum lethal dose of 1782 mg/kg bw for dogs (Von Oettingen, 1943, Val. 4). In the ECETOC JACC (2003) document also one publication with an oral LD50 in rats below 2000 mg/kg (790 mg/kg) is reported.

 

Dermal

The most reliable data were provided by a study comparable to OECD TG 402 (Union Carbide Corporation 1951). Here, butan-1 -ol was applied to the shaved skin of rabbits for 24 hours under occlusive conditions. Four doses of 1.26 to 10 ml/kg were applied to groups of four male rabbits and a LD50 value of 4.24 ml/kg bw (corresponding to ca. 3434 mg/kg bw; calculated with a density of 0.81 g/mL) was determined after an observation period of 14 days. Three rabbits of the 5 mL/kg bw group and all rabbits of the 10 ml/kg bw group died; all deaths occurred on the day of application. Body weight gain during the observation period was highly variable in the sublethal dose groups and negative in the survivor of the 5 mL/kg bw group. No information regarding clinical signs or local effects was available. In the ECETOC JACC (2003) document further dermal LD50 values in rabbits of 7600, 5300 and 4200 mg/kg are reported.

 

 

Inhalation

In a study similar to OECD TG 403, 10 Sprague-Dawley rats per sex per dose were whole-body exposed to vapour atmospheres of butan-1-ol for 4 h and observed for 14 d. The LC0 is >17.76 mg/L; no mortality or clinical signs were observed at 17.76 mg/L; only slightly reduced body weight gain was observed. Therefore, the LD50 level is considered to be > 20 mg/L (BASF 1979).

In another study, which was similar to the inhalation hazard test of OECD TG 403, 12 Sprague-Dawley rats of both sexes were exposed to a vapour saturated butan-1-ol atmosphere for 7 h. None of the animals died (BASF 1980).

Additionally, in a further study comparable to OECD TG 403 no mortalities were observed after exposure to a substantially saturated vapour for 8 hours in male rats and after exposure to 8000 ppm (ca. 24 mg/L) for 4 h in female rats, respectively. Poor coordination or prostration was observed in both trials (Union Carbide Corporation 1951).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The substance is already listed in Annex VI to Regulation (EC) No 1272/2008 and classified with Cat. 4 oral (H302:" Harmful if swallowed"). Due to the slight dermal toxicity of butan-1-ol (rabbit LD50 ca. 3430 mg/kg bw), the substance has not to be classified according to Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EC) No 2016/1179.

Due to the very low inhalative toxicity of butan-1 -ol (rat 4h LC0 vapour >=17.76 mg/l), the substance is not considered to be classified for acute inhalative toxicity under Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.

Due to the observed local irritant effects on the respiratory system in an inhalation hazard test and in humans and transient effects on the CNS (drowsiness and dizziness) the substance is classified as STOT Single Exposure Cat. 3 (H335: "May causes respiratory irritation"/H336 "May cause drowsiness or dizziness") according to 1272/2008/EC (CLP) requirements.