L-malic acid

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
EPIWIN software by US-EPA

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 97-67-6

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Decimal logarithm of the freshwater fish 96h LC50 values in milimoles per liter (mmol/L)

- Unambiguous algorithm:
log LC50(mmol/L) = -0.8799 log Kow + 1.6467 (neutral organics)
The only descriptor used in the model is octanol-water partition coefficient, log Kow. Water solubility is relevant: if the LC50 exceeds the water solubility by 10x, no effects at saturation are predicted.

- Defined domain of applicability:
In principle, each ECOSAR model is applicable for substances belonging to the respective chemical class. The class of the substance is recognized by the program itself, based on the molecular structure. If no special class can be assigned, it is assumed that the compound belongs to the “neutral organics” class. It is however possible that the compound contains structural groups not represented in the training set (or represented there in less instances), so that the toxicity can be additionally influenced. These points should be taken into account while assessing the compliance with the applicability domain of the model.

Limitations:
If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.

Additionally, the applicability domain is estimated with respect to log Kow and molecular weight.
For neutral organics, these are:
Maximum log Kow: 5.0, maximum MW: 1000 (neutral organics)

- Appropriate measures of goodness-of-fit and robustness and predictivity:
Neutral organics: N = 327+61 (number of compounds included + not included in regression equation), R2 = 0.8753 (coefficient of determination)

- Mechanistic interpretation:
For acute effects caused by neutral organics, the mechanistic interpretation is related to the partitioning of the substance from water into the lipid phase of the organism (log Kow as mechanistically justified descriptor). This relationship is extrapolated to other classes of substances and to long term effects. In those cases it is assumed that basically log Kow remains a toxicity trigger and other specific or non-specific effects are included in the QSAR equation, determining the slope and the intercept.

5. APPLICABILITY DOMAIN
- Other considerations (as appropriate):
The very low toxicity for L-malic acid predicted be the model is supported by experimental data for the very similar compound fumaric acid (CAS 110-17-8). Fumaric acid has a predicted LC50 of >100 mg/l (53316 mg/l) and experimental data confirmed the low toxicity as the LC50 is >100 mg/l (NOEC 100 mg/l) in a limit test according to OECD 203 (see dissesminated REACH dossier for fumaric acid CAS 110-17-8).

6. ADEQUACY OF THE RESULT
The substance fits in the applicability domain of the model. The prediction is valid and can be used for classification and risk assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Principles of method if other than guideline:

Calculation based on ECOSAR v1.11, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

L-malic acid

EC Number:

202-601-5

EC Name:

L-malic acid

Cas Number:

97-67-6

Molecular formula:

C4H6O5

IUPAC Name:

malic acid

Test material form:

solid

Results and discussion

Effect concentrations

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Remarks on result:

other: predicted LC50: 2.23e+006 mg/l; Chemical may not be soluble enough to measure this predicted effect

Details on results:

For detailed description on the model and its applicability, see "Any other information on materials and methods incl. tables".

Applicant's summary and conclusion

Conclusions:

The predicted LC50 for L-malic acid is significantly > 100 mg/l