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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation of the test item (represented by di-iso-tridecylamin, CAS 57157-80-9, C26H55N) in organisms is not to be expected.

Key value for chemical safety assessment

Additional information

Di-tridecylamine, branched and linear (CAS 101012-97-9) is a mixture of (predominantly) di-alkyl amines with varying alkyl-chain length in a range between C13 and C29.The main fraction consists of isomers of di-tridecylamines (C26H55N). Secondary fractions were detected to have chain lengths from C11 to C15. The following structures and relative fractions were proposed:

- Isomers of C13H29N (mono alkyl amine): 0.2%

- Isomers of C23H49-N: 0.4%

- Isomers of C24H51-N: 4.4%

- Isomers of C25H53-N: 8.7%

- Isomers of C26H55-N: 81.2%

- Isomers of C27H57-N: 3.5%

- Isomers of C28H59-N: 1.3%

- Isomers of C29H61-N: 0.2%

 

The main fraction with an amount of ca. 80% are isomers of C26H55N. For this fraction, di-iso-tridecylamine (CAS 57157-80-9) was selected as representative substance. The assessment of ecotoxicology is predominantly focussed on this molecule, especially in cases of calculations and non-BASF studies.

 

A study is not required for this tonnage band. However, data will be provided in order to discuss the bioaccumulation potential within the PBT assessment.

 

According to the analytical report 10Y03801 (BASF, 2010), the test item is a mixture of several C13-C29 compounds with isomers of C26H55N1 being the major fraction with ca. 80%. As a representative substance for these isomers di-iso-tridecylamine (CAS 57157-80-9) is used for modelling the bioaccumulation potential and other substance properties. At environmental conditions (pH 5-9) this substance is charged positively at the N-atom. The pKa was estimated at 10.80 (SPARC v4.5; BASF, 2011).

 

In order to assess the bioaccumulation potential of the mixture, the log Kow was estimated for the four representative molecules of the mixture using KOWWIN v1.67 (see IUCLID Ch. 4.7). The log Kow values, which are representative for the uncharged molecules, are above 4.5 indicating a potential for bioaccumulation. The log Kow for C13 is 5.2, for C23 10.0, for C26 11.5 and for C29 12.9. It should be noted that the log Kow estimates for the large molecules C26 and C29 are considered as less accurate as both molecules were not within the estimation domain of the KOWWIN model (see IUCLID Ch. 4.7). According to REACH Guidance document R.11, the reliability of modelled log Kow values > 10 is not known. Nevertheless, a log Kow > 10 indicates that the BCF of a substance is probably lower than 2000 L/kg (REACH Guidance document R.11).

In addition, a log Kow of 7.67 at pH 7.0 was estimated for the charged C26 molecule which represents ca. 80% of the mixture (BASF, 2011), indicating a potential for bioaccumulation. As pointed out in the REACH guidance document R.11, a decreasing relationship between the log Kow and bioaccumulation is observed at very high log Kow values of > 6.

 

Based on weight-of-evidence, it can be concluded that tridecanamine, N-tridecyl-, branched and linear (DTDA; CAS 101012-97-9), represented by di-iso-tridecylamine (CAS 57157-80-9) is not expected to significantly bioaccumulate in aquatic organisms. The majority of the reliable models predict BCF values of clearly below 2000, indicating that the substance does not fulfil the "B"-criterion. The modelled results are supported by experimental results with the analogous substances (CAS 143-27-1, n-hexadecylamine, C16) and tridecylamine, branched and linear (TDA, b+l, CAS 86089-17-0). TDA, b+l was removed from the candidates list of PBT substances by the ESIS PBT expert working group (ESIS, 2008). Considering mitigating factors like metabolism, BCF values of < 100 can be expected.

 

- A BCF calculation using the CATALOGIC v.5.11.13 BCF base-line model v02.07 is available for di-iso-tridecylamine (CAS 57157-80-9). The BCF model calculates the BCF based on user-entered data, in this case the estimated log Kow value of 7.67 for the charged molecule and the measured water solubility of 0.03 mg/L. Furthermore, the influence of mitigating factors like ionization of the molecule, water solubility, size and metabolism are also considered by the model. Taking into account these mitigating factors the BCF is reduced from an initial value of 13829 (log BCF = 4.14) to 6.2 (log BCF = 0.79), mainly due to metabolism.

Besides metabolism also the low water solubility and the molecular size reduce the log BCF as estimated by the model.

Molecular size and water solubility are discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006). The maximum diameter of the test item is determined to be 15.25 - 33.72 Å, depending on its conformation (DiamMax Average: 21.72 Å).

When used as single mitigating factors (no combination with other factors), metabolism, molecular size and water solubility reduce the overall bioaccumulation by log BCF of 1.83, 0.22 and 0.18, respectively. All in all, based on the predicted log BCF of 0.79 significant bioaccumulation is not to be expected in animal tissues. The test substance is to 100% within the applicability domain of the model (BASF, 2011).

 

- EPISuite v4.1/BCFBAFv3.01: Based on the log Kow for the charged molecule of C26 (log Kow = 7.67 at pH 7), a BCF value of 1582 L/Kg was estimated with the submodel Meylan et al. (1997/1999). This BCF estimate can be regarded as accurate as the compound was within the applicability of the model. Using the Arnot & Gobas (2003) method with included biotransormation rate estimates, the BCF was calculated to be 715 L/Kg (BASF, 2011). Although the substance was within the applicability domain of this submodel, the estimation may be less accurate due to the substance's property to appreciably ionize at physiological pH.

- BCF values were also estimated with the BCFBAF model v3.01 for the representative compounds of the mixture based on the log Kow of the uncharged molecules. The BCF estimates for C13H29N and C23H55N can be considered as accurate, while the estimates for the larger compounds are not within the model's applicability domain. Regarding the C26 and C29 compounds, it should be noted that the log Kow estimates (KOWWIN v1.67, see IUCLID Ch. 4.7) are considered as less accurate as the compounds were not within the estimation domain of the model. This is important as the BCFBAF model uses log Kow to derive the BCF values. The corresponding BCF values of the C13 to C29 compounds range from 16 to 115 L/Kg. With the Arnot-Gobas BCF method including biotransformation rate estimates the BCF was between 1 and 20 L/Kg for the di-alkylamines and 1146 L/Kg for the C13 mono alkyl amine (BASF, 2011). However, for the analogous C13-substance TDA, b+l (CAS 86189-17-0) it has been shown that the BCF is below 1000 (see below).

 

- BCF Read-Across model v1.0.2 (VEGA): A BCF of 38 L/Kg was predicted by this submodel (log BCF = 1.17). The log Kow stated by this model were 10.24 (ALogP) and 6.73 (MLogP). The result appears to be reliable as the substance was within the applicability domain (Global Applicability Domain Index > 0.7).

 

- T.E.S.T. v4.1 (US EPA model): The substance was within the applicability domain of all 5 individual methods (hierarchical clustering, single model, group contribution, FDA, nearest neighbor). The methods were validated using statistical external validation using separate training and test data sets. The Consensus method averages the reasonable results from all applicable models. Following EPA, the Consensus method yields the best results in terms of prediction accuracy and coverage. Regarding the test item di-iso-tridecylamine (CAS 57157-80-9; C26H55N), the predicted BCF values range from 11 to 545. The Consensus method resulted in a BCF of 61 (BASF, 2012). Although the substance was within the applicability domain of all models, the confidence in the results is low since the mean absolute errors (MAE) for the predictions for similar chemicals were higher than the MAE's for the entire set of chemicals. This applies to the external test set as well as to the training set.

 

- The estimations are supported by experimental results which were determined for n-hexadecylamine (CAS 143-27-1), a primary alkylamine with a C16 chain length which is an analogous substance to one of the main expected metabolite iso-TDA. The bioaccumulation was studied following OECD guideline 305. The BCF was determined to be ≥ 500 (ECHA-RAC, 2011). Read across to this substance was accepted by the competent authorities within the PBT assessment of TDA, b+l (CAS 86089-17-0), the feedstock of DTDA (CAS 101012-97-9). Based on the results of the OECD 305 with n-hexadecylamine (CAS 143-27-1), TDA, b+l (CAS 86089-17-0) was removed from the candidates list of PBT substances by the ESIS PBT expert working group (ESIS, 2008; see http://esis.jrc.ec.europa.eu/doc/PBT-evaluation/PBT_sum093_CAS_86089-17-0.pdf).

This result is also supported by a recently performed log Pow guideline study under GLP conditions according to OECD 117. The log Pow of TDA, b+l was measured to be 1.5- 2.3 at pH 7 and 23°C (BASF, 2012; report No. 12L00366). However, the measured log Kow-value is of limited value as surface tension properties of the molecule cannot be excluded (OECD 115: 29 mN/m at 20 °C (concentration 1g/l)).

 

- The expected metabolism of DTDA taken up by fish is supported by the results from a toxicokinetic study with mice. The major routes of metabolism of secondary amines involve various oxidative processes, including N-oxidation and dealkylation followed by deamination and conjugation, and other enzyme-catalysed reactions leading to detoxification and excretion.

Additionally, N-acetylation (a genetically regulated process in humans) may occur, but represents only a very minor pathway in the metabolism of aliphatic amines. In animals, aliphatic amines are metabolized to carboxylic acid and urea.

For secondary amines, metabolic intermediates are the corresponding aldehyde and ammonia. Metabolic pathways involved include (1) monoamine oxidase deamination; (2) diamine oxidase deamination; (3) N-dealkylation by cytochrome-P450; N-oxidation by cytochrome P-450 to the nitrone; and (4) N-oxidation by microsomal flavin-containing monooxygenase. The nitrones that are formed are expected to undergo rapid hydrolysis, resulting in an aldehyde or ketone (in the case of diisopropyl amine) and the corresponding hydroxylamine. The hydroxylamine may be excreted unchanged, conjugated and excreted, further oxidized or reduced to the primary amine. The primary amine is further metabolized by oxidative deamination to ammonia and an aldehyde. The aldehydes are thought to serve as substrates for aldehyde dehydrogenase catalysed oxidation to carboxylic acids. It is assumed that these metabolic steps are also applicable for the DTDA.

In a toxicokinetic study with the analogous substance feedstock of DTDA Tridecylamine (CAS 86089-17-0; TDA) it was shown that the substance was metabolised and excreted as carbon dioxide after injection of radiolabeled test item into mice (Fowler et al., 1976). The proposed metabolic pathway was the oxidative deamination by monoamine oxidase and further breakdown to carbon dioxide.

[Reference: JS Fowler et al., 1976. Carbon-11 labelled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurements in vivo. J Pharmacol Exp Ther 98 (1), 13-145.]

 

Regarding the possible metabolic pathways of secondary amines, it can be concluded that metabolism will reduce the bioaccumulation potential of the substance.