(Z)-2-butene-1,4-diol

Basic toxicokinetics

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

Test material information

Constituent 1

Reference substance name:

But-2-ene-1,4-diol

EC Number:

203-787-0

EC Name:

But-2-ene-1,4-diol

Cas Number:

110-64-5

Molecular formula:

C4H8O2

IUPAC Name:

2-Butene-1,4-diol

Constituent 2

Reference substance name:

(Z)-2-butene-1,4-diol

EC Number:

228-085-1

EC Name:

(Z)-2-butene-1,4-diol

Cas Number:

6117-80-2

Molecular formula:

C4H8O2

IUPAC Name:

but-2-ene-1,4-diol

Radiolabelling:

other: not applicable

Results and discussion

Preliminary studies:

1,4-Butenediol is expected to metabolize to maleic acid

Main ADME results

Type:

metabolism

Results:

Expected to metabolize to maleic acid

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Expected to metabolize to maleic acid

Any other information on results incl. tables

Data on the toxicokinetics of 1,4-Butenediol (B2D, CAS RN: 110-64-5) is limited and not well characterized. However, it is supported by limited test data and by some similarities to better studied substances of similar structure.  It is predicted that B2D is metabolized to maleic acid.  B2D’s toxicological profile is very similar to maleic acid’s toxicological profile.  Both substances exhibit a low order of acute toxicity as well as quite similar repeat-dose target organ toxicities.  Accordingly, B2D and maleic acid have similar ecotoxicology profiles as well (US HPV, 2002).
 
The metabolism of B2D is largely speculative but can be deduced due to the large amounts of metabolic data on other unsaturated alcohols, like ally alcohol (see attached Metabolism Profile of B2D).  B2D may be metabolized by alcohol and aldehyde dehydrogenases first to 4-hydroxycrotonaldehyde, then to the corresponding half acid.  The half acid is likely converted to the corresponding acid aldehyde then finally to maleic acid, thus the similarities in toxicological profiles between B2D and maleic acid.  Allyl alcohol, although not sharing the same toxicological profile as B2D or maleic acid, shares a similar metabolic pathway in that it is known to be acted on by alcohol and aldehydes dehydrogenases, resulting in bioactivation through similar corresponding aldehydes and acids. Allyl alcohol’s structure is similar to B2D except that it is a mono-alcohol, rather than a diol (see Metabolism Profile of B2D).
 
The absorption characteristics of B2D are unknown but thought to be (like other similar alcohols) fairly easily absorbed via the oral route.  Like many alcohols, B2D is predicted to be metabolized in the liver as noted above and to also be conjugated via glutathione-s-tranferases.  Acute oral values indicate a low to moderately toxic substance in rats and mice.  A repeat dose study demonstrated effects in male rat kidney, liver enzyme induction, and mild anemia in females.
 
B2D is likely excreted from the body via the urine as either the degradation products of maleic acid or as mercapturate-conjugated B2D.

Applicant's summary and conclusion

Conclusions:

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