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

Endpoint summary

Description of key information

The acute toxicity of 1,4-butanediol was tested under semi-static conditions in a 96-hour toxicity study on the killifish (Oryzias latipes) following OECD TG 203. Analytical verification of the test substance concentrations at test start and after renewal (48 h) revealed recovery rates of > 80 %. Based on nominal concentrations, the 96-h LC50 was determined to be > 100 mg/L. Values generated on the source substance will be directly applicable to the target substance. The predicted 96-h LC50 for acute toxicity to fish for (R)-(-)-butane-1,3-diol is > 100 mg/L.

 

The acute toxicity of 1,4-butanediol was tested under semi-static conditions in a 48-h toxicity study on the water flea (Daphnia magna) following OECD TG 202. Analytical verification of the test substance concentrations revealed recovery rates of > 80 % after 48 h. Based on nominal concentrations, the 48-h EC50 was determined to be > 1000 mg/L. Values generated on the source substance will be directly applicable to the target substance. The predicted 48-h EC50 for acute toxicity to daphnids for (R)-(-)-butane-1,3-diol is > 1000 mg/L.

  

The reproductive toxicity of 1,4-butanediol was tested under semi-static conditions in a 21-day toxicity study on the water flea (Daphnia magna) following OECD TG 202 (1984). Analytical verification of the test substance concentration was conducted and the toxicity values were based on the mean measured concentration. Based on mean measured concentration, the 21-day reproductive toxicity EC50 was determined to be > 85 mg/L and the NOEC was 85 mg/L. Values generated on the source substance will be directly applicable to the target substance. The predicted 21-day reproductive toxicity EC50 for (R)-(-)-butane-1,3-diol is >85 mg/L and the NOEC was 85 mg/L.

 

HYPOTHESIS FOR THE ANALOGUE APPROACH

Data for butane-1,4-diol (CAS No. 110-63-4) is used to address certain ecotoxicological data requirements 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 similarity of structure, physical-chemical properties and ecotoxicity of the source and target substances.

 

The algae growth inhibitory effects of (R/S)-1,3-butanediol were studied on Selenastrum sp. following OECD TG 201. A 72-hour limit test with a control (0 mg/L) and the nominal test concentration of 1000 mg/L was set up. Analytical verification of the test concentrations by GLC revealed a mean measured concentration of 1070 mg/L. Based on mean measured concentrations of (R/S)-butane-1,3-diol, the 72-h ErC50 is > 1070 mg/L and the 72-h NOErC is ≥ 1070 mg/L.  Values generated on the source substance will be directly applicable to the target substance. The predicted values for (R)-(-)-butane-1,3-diol are 72-hour ErC50 of > 1070 mg/L and the 72-hour NOErC equal to 1070 mg/L.

  

The growth inhibiting effect of (R/S)-1,3-butanediol on the ciliate Tetrahymena pyriformis was determined using the TETRATOX assay. The resulting IGC50 (40 h) of 17982 mg/L indicates no significant toxicity of (R/S)-1,3-butanediol to microorganisms (ciliates). Values generated on the source substance will be directly applicable to the target substance. The (R)-(-)-butane-1,3-diol toxicity to microorganisms is predicted to be ICG50 (40 h): 17982 mg/L.

 

HYPOTHESIS FOR THE ANALOGUE APPROACH

Data for butane-1,3-diol (CAS No. 107-88-0) is used to address certain ecotoxicological data requirements 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 algal and microbial test populations used in acute algal toxicity and activated sludge respiration inhibition studies, respectively, 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 these studies, and the experimentally determined ecotoxicity values for the source substance are therefore directly applicable to the target substance.