Registration Dossier

Administrative data

Description of key information

Oral LD50:  856 mg/kg bw
Dermal LD50: >2000 mg/kg bw (estimated); >200 mg/kg (measured)
Inhalation LC0: 1.6 mg/l

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: basic data given
Principles of method if other than guideline:
Method: other: BASF-Test
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 %
Doses:
1600, 800, 640, 400, 200 µl/kg
No. of animals per sex per dose:
1600 and 200 µl/kg: 3 animals; 800, 640 µl/kg: 10 animals; 400 µl/kg:5 animals
Control animals:
yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 856 mg/kg bw
Based on:
test mat.
Mortality:
1600 µl/kg: animal died within 24 hours; 800 µl/kg: 6 animals died after 24 hours; 640 µl/kg: 2 animals died after 24 hours, 1 animal died after 48 hours
Clinical signs:
Depression, stagger, respiration disorder
Gross pathology:
NAD

Originally: LD50 ca. 0.8 ml/kg

 Dose µl/kg  number of dead animals  1 hour  24 hours  48 hours  7 days
 1600  3/3  0/3  3/3    
 800  6/10  0/10  6/10  6/10  6/10
 640  3/10  0/10  2/10  3/10  3/10
 400  0/5        0/5
 200  0/3        0/3
 control animal          0/20
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
856 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study is comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with restrictions (partly limited documentation; nominal atmosphere concentration; vapour only). Not suitable for classification if aerosol exposure likely.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
Inhalation hazard test (Annex)
Deviations:
yes
Remarks:
nominal air concentration, vapour only
Principles of method if other than guideline:
Method: other: BASF-Test (Inhalation Risk Test)
GLP compliance:
no
Test type:
other: Inhalation Risk Test
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: conditioned air
Details on inhalation exposure:
Rats exposed for 2 h and 8 h, respectively, to a vapour saturated atmosphere.

Vapour was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The glass cylinder was heated in a water bath. The air pressure was 730 - 740 mm Hg . Temperature in the exposure chamber was 20°C.

The saturated vapour pressure was calculated to be approximately 0.024 mg/L at 20°C.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
0.024 mg/l (nominal), saturated vapour concentration at 20°C.
No. of animals per sex per dose:
3
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.024 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: Inhalation Hazard test
Mortality:
No mortality was observed.
Gross pathology:
No abnormal findings.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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: see 'Remark'
Remarks:
Non-GLP study that meets key elements of current OECD 402 guideline with some notable restrictions (8 day observation instead of 14, skin surface area <10%). Suitable for use in classification if dermal absorption rate and oral toxicity taken into account.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
8-day observation period instead of 14; skin surface area <10%, top dose was only 200 mg/kg
Principles of method if other than guideline:
Method: other: BASF-Test
GLP compliance:
no
Test type:
other: Acute dermal toxicity
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 cm²

REMOVAL OF TEST SUBSTANCE
- Washing : After the exposure time the skin was washed with detergent and water

Duration of exposure:
24 hours
Doses:
200 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No abnormal clinical signs were observed.
Gross pathology:
No abnormalities were noted at necropsy.

 Dose  Sex  1 h  24 h  48 h  8 days
 200 mg/kg  male  0/5  0/5  0/5  0/5
 200 mg/kg  female  0/5  0/5  0/5  0/5
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

1,4-Butenediol (B2D) has been adequately characterized for acute toxicity via oral, dermal, and inhalation routes. B2D is considered harmful via oral gavage, but no mortality was observed at the concentrations tested in the inhalation and dermal exposures. In rats, the oral LD50 is 856 mg/kg bw (BASF AG, 1959), the inhalation LC0 is greater than the saturation vapor concentration of 0.024 mg/l (BASF AG, 1959), and the dermal LD50 is measured to be >200 mg/kg bw (BASF AG, 1978). In addition, the dermal LD50 is expected to be >2000 mg/kg bw as estimated from a predicted Skin Permeability Coefficient (Kp) of 0.000127 cm/hr (estimated using U.S. EPA DermWin v1.43), a skin surface area of 262 cm2 (typical 200 gram rat), a product density of 1.08 gm/cm3, a log Kow of -0.9, a solubility of 619 g/liter, and using the dermal permeation uptake equation described in ConsExpo v4.1. Assuming application of 2000 mg/kg bw to 10% of the skin surface of the rat, it is predicted that the internal dose would be 388 mg/kg bw, which is well below the oral LD50 of 856 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity

Based on the results of acute oral toxicity testing (LD50, rat = 856 mg/kg-bw), the substance should be classified as Acute Toxicity, Oral-Category 4 under the EU CLP classification criteria (Regulation (EC) 1272/2008).

Acute inhalation toxicity

1,4 -Butenediol is not classifiable under the EU CLP classification criteria (Regulation (EC) 1272/2008) because no mortality was observed at a concentration up to the saturated vapor concentration (BASF AG, 1959) and exposure to aerosol or mist is not expected during normal handling and use.

Acute dermal toxicity

B2D does not meet the criteria for classification the EU CLP classification criteria (EU Regulation 1272/2008) based on a measured dermal LD50 of >200 mg/kg bw and an estimated LD50 of >2000 mg/kg bw.