Registration Dossier

Administrative data

Endpoint:
biotransformation and kinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles. Not suitable for risk assessment.

Data source

Reference
Reference Type:
publication
Title:
The toxicity of acetylenic alcohols to the fathead minnow, pimephales promelas: narcosis and proelectrophile activation.
Author:
Veith GD et al.
Year:
1989
Bibliographic source:
Xenobiotica 19: 555-565

Materials and methods

GLP compliance:
not specified
Type of medium:
other: Metabolism, QSAR

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-butyne-1,4-diol
- Analytical purity: No data

Results and discussion

Any other information on results incl. tables

Pimephales promelas:

observed LD50 (96h) = 53,6 (49.3-58.3) mg/l

predicted LD50 (96h) = 254000 mg/l (QSAR, narcosis mechanism as cause of death)

factor of 4740 between observed and predicted toxicity.

 

The increased toxicity was traced back to the metabolic transformation via the enzyme alcohol dehydrogenase (ADH) to the corresponding alpha,beta-unsaturated aldehyde; 4-hydroxy-2-butynal (4-HB). 4-HB were found to bind irreversibly to an amino acid residue on the active site of ADH leading to irreversible enzyme inhibition, which caused the toxicity.

Applicant's summary and conclusion