3,7-dimethylnona-2,6-dienenitrile

Bioaccumulation: aquatic / sediment

Description of key information

The bioaccumulation potential of Lemonile has been assessed using a weight of evidence approach. Three scientifically valid QSARs and an "in vitro to in vivo" extrapolation model gave BCF estimates ranging from 37 to 105 L/kg indicating that Lemonile has a low potential to bioaccumulate. A BCF estimate of 73 L/kg has been chosen as a relevant and reliable conservative estimate for risk assessment purposes (i.e. for assessing secondary poisoning). There is in vitro evidence that Lemonile will be metabolised in fish. Thus slightly higher BCF estimates from models which assume no metabolism and/or are based on data sets not expected to be metabolised are considered conservative and worst-case.

Lemonile is not considered to be potentially bioaccumulative for the purpose of classification and labelling according to CLP (log Kow < 4) and for the PBT assessment (log Kow < 4.5) based on its measured log Kow of 3.1 to 3.2. This is supported by the BCF estimates of 37 to 105 L/kg which are significantly lower than the threshold values of 500 (CLP) and 2000/5000 (B/vB citerion in the PBT assessment).

Key value for chemical safety assessment

BCF (aquatic species):

73 L/kg ww

Additional information

Reliable measured aquatic bioaccumulation data is not available for Lemonile. According to REACH Annex IX, information on bioaccumulation in aquatic species, preferably fish, is required for substances manufactured or imported in quantities of 100 t/y or more unless the substance has a low potential for bioaccumulation (for instance a log Kow ≤ 3). However, REACH Annex XI encourages the use of alternative information before a new vertebrate test, including fish, is conducted. Lemonile has a log Kow of 3.1 to 3.2, which falls just above the criterion for waiving this endpoint. Therefore, a weight of evidence approach has been used to assess the bioaccumulation potential of Lemonile. Bioconcentration factors in fish have been estimated using i) three commonly used and scientifically valid QSARs based on log Kow, and ii) in vitro metabolism data to refine the estimation of a partitioning based BCF.

Lemonile is a non-ionic organic substance with a measured log Kow of 3.1 to 3.2. Therefore, it falls within the general applicability domain of all the used models. The experimentally determined high quality Log Kow value of 3.2 was used as an input term in the BCF estimation models. The consensus modelling approach shows that Lemonile has a low potential to bioaccumulate. All models gave an estimated BCF of less than or equal to 105 L/kg. The BCF estimates of 105 L/kg and 79 L/kg are considered conservative and worst-case. The Arnot-Gobas BCF QSAR (assuming a biotransformation rate of zero) and the Partitioning based model (assuming no metabolism) were developed to fit upper bound BCF observations while the linear model developed by Veith et al (1979) is based on a limited data set of 56 chemicals, which are not expected to be metabolised.

In an in vitro metabolism assay using trout liver S9 fractions, the four major isomers of Lemonile demonstrated a metabolic turnover of 31.3 to 64.5% of the starting concentration within a 120 minute exposure period. The substrate depletion rates were used as input into an “in vitro - in vivo” extrapolation model to give refined BCF estimates in the range of 37-43 (fu = 1) and 65-72 (fu calculated). The latter are similar to the BCF estimates of 62 to 73 using the Arnot-Gobas BCF QSAR (including biotransformation rates) and to the BCF estimate of 60 using the BCFBAF v3.01 regression model. The highest value of 73 L/kg has been chosen as a relevant and reliable conservative estimate for risk assessment purposes.

Based on the above information, assessed together as part of an overall weight-of-evidence approach, it is concluded that there is no need to further investigate the aquatic bioaccumulation of Lemonile with fish. For classification purposes, an experimentally derived high quality Log Kow value is suitable when a measured BCF on an aquatic organism is not available. Lemonile has a measured log Kow of 3.1 to 3.2. This is below the CLP Regulation EC 1272/2008 cut-off value of ≥ 4. Thus Lemonile is not considered to have the potential to bioconcentrate for classification according to CLP.

For PBT/vPvB assessment purposes, predicted BCF estimates and log Kow may be used to provisionally assess bioaccumulation potential. Lemonile has a measured log Kow of 3.1 to 3.2, which is below the B screening criterion of > 4.5. Estimated BCF values are in the range of 37 to 105 L/kg and well below the B definitive criterion of BCF > 2000 L/kg.