Hexadecanedioic acid

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to fish, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

17/01/2019

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 limited documentation / justification

Justification for type of information:

EPISuite

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C(CCCCCCCCCCCCCCC(O)=O)(O)=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QSAR software recommended by ECHA, according to ECHA’s Guidance Chapter R6 (“QSARs and grouping of chemicals”) and Chapter R10 (“Characterisation of dose [concentration] - response for environment”).
ECOSAR uses a number of class-specific log Kow-based QSARs in order to predict the toxicity of chemicals to aquatic organisms (fish, daphnids, green algae). The QSARs are developed for chemical classes based on measured test data that have been submitted by industry to the US Environmental Protection Agency (US-EPA). ECOSAR produces warnings in several occasions (e.g. when the water solubility is very low, or when the prediction is outside the range of log Kow in the training set). The software is freely available from the US-EPA

5. APPLICABILITY DOMAIN
Not detailed by the software but no alert on the fact that the substance does not fall into the applicability domain of the model.
Moreover, the modelization is not hindered by the limitations of the model, which are:
“If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted.”

6. ECOSAR CHEMICAL CLASS: Neutral Organics-acid
As the substance doesn’t match with any ECOSAR class, the estimates were predicted using a simple non-polar narcosis model representing the baseline toxicity potential (neutral organics QSAR equations). However, the model from ECOSAR gives conservative predictions.

7. ADEQUACY OF THE RESULT
The prediction is adequate as the QSAR model is scientifically valid and relevant for the regulatory purpose.

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance chap R6 "QSAR and grouping of chemicals"

GLP compliance:

no

Key result

Dose descriptor:

other: chronic value (geometric mean of LOEC and NOEC)

Effect conc.:

1.23 mg/L

Remarks on result:

ChV (chronic value, QSAR)

Details on results:

As the substance doesn’t match with any ECOSAR class, the estimates were predicted using a simple non-polar narcosis model representing the baseline toxicity potential (neutral organics QSAR equations). Nevertheless, the acute toxicity on fish predicted by ECOSAR for hexadecanedioic acid is widely higher than acute toxicity data from experimental studies (derived from the read across category approach). Therefore, it can be considered that the model from ECOSAR gives conservative predictions for for hexadecanedioic acid. Therefore, even if the substance does not belong to any ECOSAR class, the predictions can be used as a supportive information to conclude on this endpoint.

Conclusions:

As the substance doesn’t match with any ECOSAR class, the estimates were predicted using a simple non-polar narcosis model representing the baseline toxicity potential (neutral organics QSAR equations). Nevertheless, the acute toxicity on fish predicted by ECOSAR for hexadecanedioic acid is widely higher than acute toxicity data from experimental studies (derived from the read across category approach). Therefore, it can be considered that the model from ECOSAR gives conservative predictions for hexadecanedioic acid. Therefore, even if the substance does not belong to any ECOSAR class, the predictions can be used as a supportive information to conclude on this endpoint.
As the chronic value (geometric mean of LOEC and NOEC) on fish given by ECOSAR is higher than 1 mg/L and as hexadecanedioic acid is readily biodegradable, hexadecanedioic acid is not expected to have a long-term toxicity on fish.

Reference 2

Endpoint:

long-term toxicity to fish, other

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 3

Endpoint:

long-term toxicity to fish, other

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
Dicarboxylic acids are organic compounds that contain two carboxylic acid functional groups. They have the general type formula HOOC-(CH2)n-COOH. The present defined category comprises dicarboxylic acids with straight carbon chain having a “n” value from 6 to 16.
The physical and chemical properties as well as the toxicology and environmental fate and effects show that substances in this category have a similar order of toxicological and environmental fate properties, which supports the grouping of these substances as a category. (see attached justification)

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
There are number of unifying considerations justifying the similarity between these substances in some important aspects. These include:
(1) Similarity of Use: these dicarboxylic acids have several industrial uses in the production of adhesives, plasticizers, lubricants, copolymers (such as polyamides and polyesters), etc.
(2) Similarity of Functional groups: all these substances contain two common functional groups (2 carboxyl groups). The only difference between the substances of this group lies in the length of the carbon chain.
(3) Similarity of Physical / Chemical properties: the similarity of physical / chemical properties for these substances (see attached justification)
(4) Similarity of Metabolism: Dicarboxylic acids were shown to be rapidly absorbed from the gastrointestinal tract, introduced into the fatty acid catabolism and therefore extensively metabolized by the organism and excreted (Passi, S. et al, 1983).
(5) Similarity of Mammalian Toxicity: The constituents of this class have similar toxicological properties. They are not acutely toxic, irritating to skin or sensitizing. However, they all present, except for dodecanedioic acid, irritating effects on the eyes (from moderate to high effects). They do not produce systemic effects in repeated dose studies. They are neither mutagenic nor carcinogenic and do not produce developmental/reproductive toxicity. (see attached justification)
(6) Similarity of Environmental Toxicity and Fate Properties: The substances in this category have similar environmental effects properties. The environmental effects data are similar for most category members in that most members do not exhibit acute toxicity. (see attached justification)

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Remarks on result:

other: Based on the aquatic acute toxicity values of dicarboxylic analogues (LC50 > 100 mg/L) and the fact that the analogues are readily biodegradable, no aquatic chronic toxicity is expected for diacrboxylic acids.

Conclusions:

Based on the experimental acute toxicity studies on fish performed on dicarboxylic acids analogues (DC10 and DC12) and the read across category approach, hexadecanedioic acid is not expected to have a long-term toxicity on fish. Therefore, the substance is not expected to be classified for chronic aquatic toxicity.

Description of key information

A study of the long term toxicity on fish of hexadecanedioic acid does not need to be performed according to Column 2 of Annex IX of REACH Regulation 1907/2006, since the chemical safety assessment does not indicate a risk for aquatic organisms.

Indeed, a QSAR prediction using ECOSAR model was done on hexadecanedioic acid and showed that the chronic value for fish was 1.23 mg/L (prediction for neutral organics-acid class). This estimate being very conservative and the substance being readily biodegradable, hexadecanedioic acid is not expected to have long term effects on fish. Hexadecanedioic acid is not expected to be classified for aquatic chronic toxicity.

Besides, the aquatic acute toxicity on fish of other dicarboxylic acids (DC10, DC12) show LC50 > 100 mg/L. Considering these data and the ready biodegradability of dicarboxylic acids, no classification for aquatic chronic toxicity is expected. Thus, based on the read across category approach on dicarboxylic acids, hexadecanedioic acid is not expected to be toxic for the aquatic species on the long term. Hexadecanedioic acid is therefore not classified for aquatic chronic toxicity.