(R)-(-)-butane-1,3-diol

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Data for butane-1,3-diol (CAS No. 107-88-0) is used to address the ready biodegradability data requirement for (R)-(-)-butane-1,3-diol (CAS No. 6290-03-5) in an analogue read-across approach. The basis for this read-across approach is the extreme structural similarity of the source and target substances, in that the source substance is a racemic mixture of a pair of enantiomers, whereas the target substance is solely the R-enantiomer of that source pair. Two compounds that are enantiomers of each other have the same physical properties, except for the direction in which they rotate polarized light and how they interact with different optical isomers of other compounds (ECHA, 2008). Passive absorption of a substance into a test species and distribution through its tissues are governed by the physical-chemical properties of the substance, particularly its molecular size, log P, and water solubility (ECHA, 2014), and are therefore expected to be exactly the same for both enantiomers. The R-enantiomer half of the source substance and all of the target substance have been shown to metabolise in a mammalian system to a physiological ketone body, whereas the S-enantiomer of that ketone body derived from the other half of the source substance has been shown to metabolise into a compound that is not naturally present, but which can still be utilized by a less direct pathway (Desrochers et al., 1992). On the premise that the mixed microbial inoculum used in biodegradation studies will possess a considerably broader range of enzymes than a mammalian system, the minor difference in the rates of metabolism of the two enantiomers observed by Desrochers et al. (1992) is not expected to exist in their biodegradation rates, and the experimentally determined “readily biodegradable” result for the source substance is therefore directly applicable to the target substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target Substance: (R)-(-)-butane-1,3-diol 228-532-0 6290-03-5
Source Substance: butane-1,3-diol 203-529-7 107-88-0
See attached Justification for Read-Across of Ready Biodegradability Data for further details.

The target substance is known to be of high purity (≥99 % w/w), so the low levels of impurities it could contain are not expected to substantially affect its biodegradability. The purities of the samples of source material that were tested are not specifically known, but it is assumed that they would not have been sufficiently impure as to substantially affect the study results. On this basis, the applicability of the data on the source substance to the target substance is not expected to be compromised by the presence of impurities in either substance.

3. ANALOGUE APPROACH JUSTIFICATION
The basis for this read-across approach is the extreme structural similarity of the source and target substances. Specifically, the source substance is a racemic mixture of a pair of enantiomers, whereas the target substance is solely the R-enantiomer of that source pair. The source substance is therefore nominally comprised 50% of the target substance itself (the R-enantiomer), and 50% of its mirror image (the S-enantiomer), which differs from the target substance only in the chirality of one carbon atom. The selection of this source substance is justified on the basis that there is no other source substance that could possess a greater degree of structural similarity to the target substance.

Enantiomers are two stereoisomers that are related to each other by a reflection: they are mirror images of each other. Every stereocentre in one has the opposite configuration in the other. Two compounds that are enantiomers of each other have the same physical properties, except for the direction in which they rotate polarized light and how they interact with different optical isomers of other compounds (ECHA, 2008). Passive absorption of a substance into a test species and distribution through its tissues are governed by the physical-chemical properties of the substance, particularly its molecular size, log P, and water solubility (ECHA, 2014), and are therefore expected to be exactly the same for both enantiomers.

In a mammalian system, both enantiomers have been shown to be taken up by the liver and converted to their respective 3-hydroxybutyrate (beta-hydroxybutyrate; BHB) at identical rates. The target substance and one half of the source substance are converted into R-BHB, and the other half of the source substance is converted into S-BHB. R-BHB is a physiological ketone body, whereas S-BHB is not naturally present, but can still be utilized by a less direct pathway (Desrochers et al., 1992). On the premise that the mixed microbial inoculum used in biodegradation studies will possess a considerably broader range of enzymes than a mammalian system, the minor difference in the rates of metabolism of the two enantiomers observed by Desrochers et al. (1992) is not expected to exist in their biodegradation rates, and the result of “readily biodegradable” determined experimentally for the source substance is therefore directly applicable to the target substance.

4. CONCLUSION
On the basis of the information presented above, it is considered appropriate and scientifically justifiable to use the available ready biodegradability data for the source substance to address the ready biodegradability endpoint for the target substance.

REFERENCES
Desrochers S, David F, Garneau M, Jetté M, Brunengraber H (1992). Metabolism of R- and S-1,3-butanediol in perfused livers from meal-fed and starved rats. Biochem J 285:647-653.

ECHA (2008). Guidance on information requirements and chemical safety assessment. Chapter R.6: QSARs and grouping of chemicals. May 2008. Available at: https://echa.europa.eu/documents/10162/13632/information_requirements_r6_en.pdf

ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. Volume 2.0, November 2014. Available at: https://echa.europa.eu/documents/10162/13632/information_requirements_r7c_en.pdf/e2e23a98-adb2-4573-b450-cc0dfa7988e5

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Specific details on test material used for the study:

(R)-(-)-Butane-1,3-diol value is read-across from supporting (R/S)-butane-1,3-diol (203-529-7; 107-88-0) data.

Parameter:

% degradation (CO2 evolution)

Value:

28

Sampling time:

4 d

Parameter:

% degradation (CO2 evolution)

Value:

56

Sampling time:

10 d

Parameter:

% degradation (CO2 evolution)

Value:

66

Sampling time:

14 d

Parameter:

% degradation (CO2 evolution)

Value:

80

Sampling time:

24 d

Key result

Parameter:

% degradation (CO2 evolution)

Value:

80.5

Sampling time:

28 d

Validity criteria fulfilled:

not specified

Remarks:

Validity criteria were not specifically mentioned in the source summary document; however, the summary does state "Valid, without restrictions".

Interpretation of results:

readily biodegradable

Conclusions:

it is considered appropriate and scientifically justifiable to use the available ready biodegradability data for the source substance to address the ready biodegradability endpoint for the target substance. In this regard, based on the results of a key GLP-compliant study that was conducted according to OECD guideline 301 B / EU Method C.4-C, the target substance can be concluded to be readily biodegradable.

Executive summary:

The ready biodegradability of (R/S)-1,3-butanediol was studied in a Modified Sturm Test following OECD 301B. The test substance was degraded to 81% (CO2/ThCO2) after 29 days. The 10-days window was met. 1,3-Butanediol is readily biodegradable according to OECD criteria.

 

It is considered appropriate and scientifically justifiable to use the available ready biodegradability data for the source substance to address the ready biodegradability endpoint for the target substance. In this regard, based on the results of a key GLP-compliant study that was conducted according to OECD guideline 301 B / EU Method C.4-C, the target substance can be concluded to be readily biodegradable.

Description of key information

The ready biodegradability of (R/S)-1,3-butanediol was studied in a Modified Sturm Test following OECD 301B. The test substance was degraded to 81% (CO2/ThCO2) after 29 days. The 10-days window was met. 1,3-Butanediol is readily biodegradable according to OECD criteria.

 

It is considered appropriate and scientifically justifiable to use the available ready biodegradability data for the source substance to address the ready biodegradability endpoint for the target substance. In this regard, based on the results of a key GLP-compliant study that was conducted according to OECD guideline 301 B / EU Method C.4-C, the target substance can be concluded to be readily biodegradable.

HYPOTHESIS FOR THE ANALOGUE APPROACH

Data for butane-1,3-diol (CAS No. 107-88-0) is used to address the ready biodegradability data requirement for (R)-(-)-butane-1,3-diol (CAS No. 6290-03-5) in an analogue read-across approach. The basis for this read-across approach is the extreme structural similarity of the source and target substances, in that the source substance is a racemic mixture of a pair of enantiomers, whereas the target substance is solely the R-enantiomer of that source pair. Two compounds that are enantiomers of each other have the same physical properties, except for the direction in which they rotate polarized light and how they interact with different optical isomers of other compounds (ECHA, 2008). Passive absorption of a substance into a test species and distribution through its tissues are governed by the physical-chemical properties of the substance, particularly its molecular size, log P, and water solubility (ECHA, 2014), and are therefore expected to be exactly the same for both enantiomers. The R-enantiomer half of the source substance and all of the target substance have been shown to metabolise in a mammalian system to a physiological ketone body, whereas the S-enantiomer of that ketone body derived from the other half of the source substance has been shown to metabolise into a compound that is not naturally present, but which can still be utilized by a less direct pathway (Desrochers et al., 1992). On the premise that the mixed microbial inoculum used in biodegradation studies will possess a considerably broader range of enzymes than a mammalian system, the minor difference in the rates of metabolism of the two enantiomers observed by Desrochers et al. (1992) is not expected to exist in their biodegradation rates, and the experimentally determined “readily biodegradable” result for the source substance is therefore directly applicable to the target substance.

Key value for chemical safety assessment

Biodegradation in water:

readily biodegradable