O,O,O-tris(2(or 4)-C9-10-isoalkylphenyl) phosphorothioate

Bioaccumulation: aquatic / sediment

Description of key information

The substance and its constituents do not accumulate in organisms. 

Additional information

The bioaccumulative potential of the substance was assessed in a weight of evidence approach including experimental data, several QSAR estimations and data on the molecular size and log Kow. The substance is an UVCB, therefore 5 probable structures were assessd by QSAR. The single results are summarized in the table below.

Overview on BCF Results

Model	Structure 1	Within AD	Structure 2	Within AD	Structure 3	Within AD	Structure 4	Within AD	Structure 5	Within AD
Catalogic	7.41	yes	7.41	yes	7.41	yes	7.41	yes	7.41	yes
BCFBAF (EpiSuite)	3.2	no	3.2	no	3.2	no	3.2	no	3.2	no
Caesar (Vega)	7.0	no	5.0	no	5.0	no	8.0	no	2.0
Meylan (Vega)	3.0	no	3.0	no	3.0	no	3.0	no	3.0	no
KNN/Read-Across (Vega)	102.3	could be outside	102.3	could be outside	102.3	could be outside	89.1	could be outside	102.3	could be outside
T.E.S.T	586.5	yes	757.6	yes	761.2	yes	2322.5	yes	66.9	yes
Bioaccumulation study with carp, Mitsubishi, 3B567G, 1994	BCF: 48 Remarks: 0.5 mg/L and 0.05 mg/L, vehicle
Overall conclusion	BCF < 500		BCF < 500		BCF < 500		BCF < 500		BCF < 500

 

In a guideline study conducted according to OECD 305 C carp were exposed to the substance in a flow-through system. Two substance concentrations were tested (0.5 mg/L and 0.05 mg/L). The solubility of the test substance was enhanced by addition of a solubiliser.

Based on whole body weight of fish a BCF of 48 was determined (Ciba-Geigy, 1994), demonstrating that the substance is not bioaccumulative.

QSAR model calculation for the 5 probable structures support the findings in the BCF study.

The BCF base-line model integrated in Catalogic is a sophisticated model which takes into account different mitigating factors, i.e. acids, metabolism, phenols, size and water solubility. The five structures were inside the parametric and the mechanistic domains of the compound with 82% of the fragments of the target chemical being present in correctly predicted training chemicals. Nevertheless, the result is regarded as reliable and suitable to be used in a weight of evidence approach together with the in vivo results. With mitigating factors applied the BCF is determined as 7.41 for all five structures. The only influence on the bioaccumulative potential has the water solubility. Furthermore, even without considering any mitigating factors the BCFmax is only at 9.14 L/kg.

 

US EPA’s Toxicity Estimation Software Tool (T.E.S.T.) uses five submodels to estimate the BCF of the target chemical. These results are than averaged in the consensus approach to provide a higher reliability. With the exception of the Single Model, the target compound is inside of the applicability domain of the single submodels. However, the confidence in the estimated BCF values of the Single submodels is not optimal. The consensus model predicts the BCF by calculating the average of the predicted BCF values from the other QSAR methodologies while taking the applicability domain of the models into account. This method typically provides the highest prediction accuracy since errant predictions are dampened by the predictions from the other methods. In addition this method provides the highest prediction coverage because several methods with slightly different applicability domains are used to make a prediction. The averaged result of the consensus method was a BCF in the range of 66.9 to 2322.5.

 

US EPA’s EPISuite includes the regression-based estimation and the Arnot-Gobas model which takes biotransformation processes into account. The five structures of the substance are within the molecular weight range but outside the log Kow range of both the regression-based estimation and the Arnot-Gobas model. The regression-based model predicted a BCF of 3.2 L/kg. The Arnot-Gobas model predicted BCF value of 0.9 L/kg for the upper trophic level including biotransformation rate estimates and biotransformation rates of zero. The EPISuite results were regarded as suitable in the weight of evidence approach.

 

The VEGA package includes three different estimations tools with each of them providing detailed information on the applicability domain. Although the substance was out of the applicability domain of the models the results fit to the results of the other models and the experimental study. Therefore, the results were taken into account in the weight of evidence approach. The BCF was estimated to be in the range of 2.0 to 102.3 L/kg. 

 

According to ECHA’s Guidance on Information Requirements and Chemical Safety Assessment chapter R.11 – PBT Assessment, compounds with an average maximum diameter of >1.7 nm together with molecular weight of greater than 1100 are unlikely to have a BCF of >2000. Although the five probable structures of the UVCB substance has a molecular weight of only 721 the DiamMax-average ranges between 21.448 and 26.875 Angstrom and even the DiamMax-Min ranges between 17.799 and 20.716 Angstrom for all five structures.

Furthermore, the aquatic BCF of a substance is probably lower than 2000 if the calculated logKow is higher than 10. The present compound has a calculated logKow of > 19.

In conclusion, using all available data in a weight of evidence approach, the compound has only a low bioaccumulative potential (BCF < 500).

Evaluation of minor constituents:

It can be concluded that also the minor constituents do not fullfil the B or vB criteria. Catalogic calculations with structure 6 are partially out of the domain of the model but the molecular size the molecular size is in the same range as structures 1 to 5 and therefore unlikely to cross biological membranes. Both constituents are therefore not relevant for the PBT assessment and not further assessed.

The substance and its constituents do not fullfill the criteria for bioaccumulative or very bioaccumulative according to REACH.

Model	Structure 6	Within AD	Structure 7	Within AD
Catalogic	7.41	no	446.7	yes
DiamMax-Average	24.730	yes	13.897	yes
Overall conclusion	BCF < 500		BCF < 500

QSAR-disclaimer

 

In 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 the substance (Q)SAR results were used for aquatic 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 aquatic bioaccumulation are not provided.