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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation in organisms is not to be expected.

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Additional information

QSAR-disclaimerIn Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort. According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided. For the assessment of Isophorone diamine (CAS 2855-13-2)(Q)SAR results were used for bioaccumulation.The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment. Therefore,and for reasons of animal welfare, further experimental studies on bioaccumulationare not provided.Assessment of the parent compound:In accordance with column 2 of REACH Annex IX, the study does not need to be conducted since the substance has a log Kow less or equal than 3. Isophorone diaminehas a measured log Kow of 0.99 (Hüls Infracor GmbH 1998) However, in order to assess the bioaccumulation potential of the test substance, the BCF was calculated with several estimation models. The table below lists the applied (Q)SAR models, the estimated BCF values and basic information on the applicability domain (AD). Detailed information on the model’s results and the AD are given in the endpoint study records of IUCLID Chapter 5.3.1. The selected models comply with the OECD principles for (Q)SAR models. Summary of relevant information on aquatic bioaccumulation: Predicted BCF values for applied QSAR models sorted by BCF (AD = Applicability Domain)ModelBCFIn ADRemarks / RestraintsBCFBAF v3.01 (EPI Suite v4.11):Arnot-Gobas BCF, upper trophic, incl. biotransformation1.9no- the substance doesappreciably ionize atphysiological pH.- maximum number ofinstances of biotransformationfragments in a training set compound was exceededBCFBAF v3.01 (EPI Suite v4.11):Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero1.9no- the substance doesappreciably ionize atphysiological pH.KNN/Read Across v1.1.0(VEGA v1.1.3)2.6no- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar moleculeshas a moderate valueCAESAR v2.1.14 (VEGA v1.1.3)3no- only moderately similar compounds have been found- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar moleculeshigh valueBCFBAF v3.01 (EPI Suite v4.11):Meylan et al. 1997/19993.2yes---BCF baseline model v02.09(OASIS Catalogic v5.11.19): incl. mitigating factors6.9no25% of fragments not present in the training setMeylan v1.0.3 (VEGA v1.1.3)8no- only moderately similar compounds have been found- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar moleculeshigh value- reliability of logP value used by the model is not adequateT.E.S.T. v4.2.1:Consensus method9.3yes---BCF baseline model v02.09(OASIS Catalogic v5.11.17): not considering mitigating factors14.6no25% of fragments not present in the training setConsidering all of the applied (Q)SAR models, the calculated BCF values range from 1.9 to 14.6 L/kg, indicating a low potential for bioaccumulation. In addition, IPDA has a measured log Kow of 0.99(Hüls Infracor GmbH 1998), which is clearly≤ 3.Assessment of relevant metabolitesThe model Catalogic 301 C v09.13 (OASIS Catalogic v5.11.19) calculated 112 metabolites of IPDA, identifying 40 metabolites as relevant degradation products, with an estimated quantity of ≥ 0.1%(for details see ‘Attached background material’ of the respective Endpoint Study Record in IUCLID chapter 5.2.1).Overall, the 112 modelled degradation products of IPDA were estimated to exhibit log Kow values in a range of -4.39 to 2.85, which is≤3. However, three relevant metabolites were predicted by the model to exhibit a higher log Kow than the parent compound itself (log Kow of the metabolites between 2.43 and 2.85). Therefore, the BCF of those metabolites was estimated with the model BCFBAF v3.01 (EPI Suite v4.11). The estimated BCF values are summarized in the table below:Summary of relevant information on aquatic bioaccumulation: Predicted BCF values of the metabolites for applied QSAR models (AD = Applicability Domain)ModelBCFIn ADRestraintsMetabolite #73BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation59.98no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero76.22no- the substance ionizes at physiologically relevant pHMetabolite #85BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation55.59no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero62.82no- the substance ionizes at physiologically relevant pHMetabolite #105BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation25.6no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero29.74no- the substance ionizes at physiologically relevant pHConsidering all of the applied (Q)SAR models, the calculated BCF values of the relevant metabolites range from 3.2 to 76.2 L/kg, indicating a low potential for bioaccumulation.ConclusionBased on the available information on the log Kow of the parent compound and the relevant metabolites, and supported by a weight -of-evidence approach from calculated data, it can be concluded that significant accumulation in organisms is not to be expected.