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EC number: 228-085-1 | CAS number: 6117-80-2
Endpoint summary
Administrative data
Link to relevant study record(s)
- 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
- 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
- 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
Referenceopen allclose all
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.
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.
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