Registration Dossier

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

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.
Principles of method if other than guideline:
Estimated from known biochemical processes
GLP compliance:
no
Radiolabelling:
other: not applicable
Preliminary studies:
1,4-Butenediol is expected to metabolize to maleic acid
Type:
metabolism
Results:
Expected to metabolize to maleic acid
Metabolites identified:
yes
Details on metabolites:
Expected to metabolize to maleic acid

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.

Conclusions:
Interpretation of results (migrated information): other: Not expected to bioaccumulate
Endpoint:
dermal absorption
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Accepted method of estimation for risk assessment
Qualifier:
according to
Guideline:
other: Estimated using U.S. EPA DERMWIN v1.43a (September 2008)
Principles of method if other than guideline:
The Dermal Permeability Coefficient Program (DERMWIN) estimates the dermal permeability coefficient (Kp) and the dermally absorbed dose per event (DAevent) of organic compounds.
GLP compliance:
no
Radiolabelling:
no
Species:
other: Estimate
Strain:
other: Estimate
Details on study design:
Log Kow (user-entered): -0.9 (used in Kp calculations)

GENERAL Equation: log Kp = -2.72 + 0.71 log Kow - 0.0061 MW

ALCOHOL Class Equation: log Kp = 0.544 log Kow - 2.884

GENERAL Equation:  Kp (predicted): 1.27e-004 cm/hr

Alchol Class Equation: Kp (predicted): 4.2e-004 cm/hr

Dermally Absorbed Dose per Event:

  Water Conc (mg/cm3): 7.4e+002 (estimated by program)

  Event Duration (hr): 1

  DA(event): 0.094 mg/cm2-event (using Fick's first law)

  DA(event): 0.15 mg/cm2-event (using eqn 5.20 & 5.21)

                  (tau = 0.3 hr, t* = 0.72 hr)

 

Description of key information

Short description of key information on bioaccumulation potential result: 
Expected to be metabolized to maleic acid.
Short description of key information on absorption rate:
Dermal Absorption Rate (Estimated): 0.094 mg/cm2-hr.
Permeation Coefficient (Estimated): 1.27e-004 cm/hr

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Data on the toxicokinetics of 1,4-Butenediol (B2D) 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.
 
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.  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.
 
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. B2D is likely excreted from the body via the urine as either the degradation products of maleic acid or as mercapturate-conjugated B2D.

Using U.S. EPA DERMWIN v1.43a, the dermal absorption rate of 1,4 -Butenediol is estimated to be 0.094 mg/cm2 -hr, which equates to a permeation coefficient (Kp) of 0.000127 cm/hr (ISP, 2010). No measured data, of sufficient reliability, are available.

Discussion on bioaccumulation potential result:

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.

Discussion on absorption rate:

Using U.S. EPA DERMWIN v1.43a, the dermal absorption rate of 1,4 -Butenediol is estimated to be 0.094 mg/cm2 -hr, which equates to a permeation coefficient (Kp) of 0.000127 cm/hr (ISP, 2010). No measured data, of sufficient reliability, are available.