Hexanoic acid, 3,5,5-trimethyl-, 2,2,6,6-tetramethyl-1-[2-[(3,5,5-trimethyl-1-oxohexyl)oxy]ethyl]-4-piperidinyl ester

Bioaccumulation: aquatic / sediment

Description of key information

The test substance does not accumulate in organisms.

Additional information

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 test 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.

 

Additionally, a study on bioaccumulation was conducted for the Japanese authorities (Institute of Ecotoxicology Co., Ltd. 2015). Since the test substance is a reaction product consisting of 13 peak components in this concentration test, bioconcentration of each peak was evaluated using GC except for Peak 1 and Peak 2 whose biodegradabilities were confirmed in the biodegradability test. Two concentrations of the test substance in water were set up (0.5 mg/L for the high exposure level (Concentration Level 1) and 0.05 mg/L for the low exposure level (Concentration Level 2)). Even though the test concentrations are above the water solubility due to the use of an emulsifier, the test results can be used in a weight of evidence. In particular, since the concentration of every peak was determined ih the test water and in the fish and the BCF values were determined for each peak. Therefore, the values refer to the concentration of every peak in the test water and are not releated to the given test concentration values. According to the results of the bioconcentration test, the bioconcentration factors (BCFs) of all the peaks except for biodegradable Peak 1 and Peak 2 in both Concentration Levels were less than 50- fold during the 28-day exposure period. Thus, the steady state was assumed to be achieved on the 28th day of exposure. After 28 d of exposure a low potenial for bioaccumulation was determined for every peak. The maximum BCF values are < 29 determined in the concentration level 2. Therefore, the test substance is regarded as not bioaccumulative since the BCF values of all paeks are < 29.

To support these findings four QSAR calculations have been conducted. The single models and their results are summarized in the table below:

Model		BCF	Log BCF	Remarks
Catalogic v5.11.16		6.46	0.81	all mitigating factors applied; 91 % in domain
T.E.S.T. v4.01		75.23	1.88
EPISuite v4.10	Regression-based estimate	1962	3.293	The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor
	Arnot-Gobas upper trophic level	1.705	0.232	Including biotransformation rate estimates; MW and log Kow are within the range of training set.
	Arnot-Gobas mid trophic level	2.048	0.311	Including biotransformation rate estimates; MW and log Kow are within the range of training set.
	Arnot-Gobas lower trophic level	2.171	0.337	Including biotransformation rate estimates; MW and log Kow are within the range of training set.
VEGA CAESAR v2.1.13		7	0.82	The test substance is out of model Applicability Domain

Regarding the results of the model calculation, the calculated BCF values range from 6.46 (Catalogic) to 1962 (EPISuite Regression-based estimate). Of these models, Catalogic, VEGA CAESAR and the Arnot-Gobas model from EPISuite v4.10 take into account mitigating factors, e.g. metabolism, water solubility and/or size.

Catalogic revealed a corrected BCF of 6.46 and the compound is 91 % within the model’s applicability domain.

The Arnot-Gobas model from the EPISuite takes into account the biotransformation rate of the compound and calculates BCF values for the upper, mid and lower trophic levels. The values for the present compound range from 1.705 (upper trophic level) to 2.171 (lower trophic level). The model assumes default lipid contents of 10.7%, 6.85% and 5.98% for the upper, middle and lower trophic levels, respectively. Usually, in the context of REACH a default lipid value of 5% is assumed which represents the average lipid content of the small fish used in OECD 305 studies. Thus, the higher lipid values of the Arnot-Gobas model can be regarded as reasonable worst-case scenarios as higher lipid contents are usually associated with a higher potential for bioaccumulation. The MW and the log Kow are within the range of training set.

The regression-based estimate from the EPISuite revealed a BCF value of 1962 based on a calculated logKow and the test substance is in the applicability domain of the model. However, the program does not take the biotransformation rate into account and the value is only based on a calculated logKow. Due to this fact, this value is not a realistic BCF value and it is not consistent with the results of the other QSAR calculations.

The T.E.S.T. package from the US EPA estimates BCF values using several different advanced QSAR methodologies. The recommended model of the T.E.S.T. package is the consensus method since it provides the most accurate prediction. This model estimates the BCF by taking an average of the predicted BCF values from the other applicable QSAR methods of the package. For the present substance the consensus method averaged the results from (1) the hierarchical clustering method, (2) the single model method, (3) the group contribution method, (4) the FDA method and (5) the nearest neighbor method. The resulting BCF value is 75.23.

The VEGA model was developed with several descriptors and is based on a dataset of 473 compounds. It offers detailed information on the applicability domain. In the present case, the calculation gave a BCF value of 7. Since the Global AD Index was calculated to be 0.442 the substance is out of the Applicability Domain of the model.

However, even though the test substance was out of the Applicability Domain of some programs, the QSAR results support the overall conclusion that the test substance is not bioaccumulative, since all QSAR models give a value below a BCF of 100 (except for the regression-based estimate) and the results of the models were the applicability domain is met are consistent with the results of all models and the preliminary results of the bioaccumulation study .

In overall conclusion, considering the test results and the QSAR calculations it can clearly be stated that test substance is not bioaccumulative according to PBT-criteria and the BCF value is below 100.