Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Estimated from known biochemical processes
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on limited information on the parent compound but executed with scientific rigor and other known metabolic pathways.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2010

Materials and methods

Principles of method if other than guideline:
Estimated from known biochemical processes
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
other: not applicable

Results and discussion

Preliminary studies:
1,4-Butynediol is expected to metabolize to 4-hydroxy-2-butynaldehyde (4-OH-butynal) and potentially further to 4-hydroxy-2-butyne-monocarboxylic acid and further yet to 2-butyne-1,4-dicarboxylic acid.
Main ADME results
Type:
metabolism
Results:
Expected to metabolize to 4-hydroxy-2-butynaldehyde (4-OH-butynal) and potentially further to 4-hydroxy-2-butyne-monocarboxylic acid and further yet to 2-butyne-1,4-dicarboxylic acid.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Expected to metabolize to 4-hydroxy-2-butynaldehyde (4-OH-butynal) and potentially further to 4-hydroxy-2-butyne-monocarboxylic acid and further yet to 2-butyne-1,4-dicarboxylic acid.

Any other information on results incl. tables

The metabolism of 2-butyne-1,4-diol (B3D) is largely unknown. However, in a literature review by NIEHS (1997), it is indicated that B3D will be metabolized, via alcohol dehydrogenase (ADH), to a more toxic metabolite. In Wistar rats, B3D administered intraperitoneally (i.p.), induced mortality in a dose-dependent fashion, while pretreatment with pyrazole (an inhibitor of liver ADH) prevented death. Pretreatment with pyrazole prevented also the induction of marked behavioral effects. Using rat liver extract, it was shown that B3D was a substrate for ADH, and that pyrazole competitively inhibited the oxidation and, therefore, the metabolism of B3D (NIEHS, 1997).

 

It is proposed that B3D is likely metabolized, via ADH, to 4-hydroxy-2-butynaldehyde (4-OH-butynal). Whether 4-OH-butynal is the ultimate toxicant is unknown. 4-OH-butynal could be further metabolized to its corresponding half acid, 4-hydroxy-2-butyne-monocarboxylic acid, via aldehyde dehydrogenase (ALDH). This 4-hydroxy-monoacid could potentially be further metabolized, via ADH and ALDH to the 2-butyne-1,4-dicarboxylic acid (see Figure), following the general scheme attributed to many alkyl diols.

 

Additionally, the B3D EU Risk Assessment Report (ECB, 2005) suggests that Cytochrome P450 dependent metabolism may also play a role in B3D conversion because a low increase in aminopyrine demethylase has been reported after B3D administration. The potential role of metabolism via glutathione has not been reported.

References:

NIEHS, 1977 - Toxicology of 2-Butyne-1,4-diol [110-65-6], Review of Literature. National Institute of Environmental Health Sciences, PO Box 12233 Research Triangle Park, North Carolina 27709, Contract No. N01-ES-65402 ILS Project No. L082, Submitted by Raymond Tice, Ph.D. Integrated Laboratory Systems Post Office; January 14, 1997. Available online at: http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/2-Butyne-1,4-diol.pdf

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Not expected to bioaccumulate