Dodecanal

Bioaccumulation: aquatic / sediment

Description of key information

The bioaccumulation potential of dodecanal has been assessed using a weight of evidence approach. An in vitro study showing rapid metabolism supports a reduced BCF compared to estimates based only on Log Kow.  A regression QSAR corroborated with analogue data and models that take biotransformation into account all give BCF estimates below the REACH PBT B-criterion of 2000 L/Kg. The BCF estimates range from 34 to 711 L/kg. A cautious approach has been taken and the highest, valid estimate has been chosen as the key value for chemical safety assessment. 

Key value for chemical safety assessment

BCF (aquatic species):

711 L/kg ww

Additional information

Reliable measured aquatic bioaccumulation data is not available for dodecanal. 

According to REACH Annex IX, information on bioaccumulation in aquatic species, preferable 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 and according to the Integrated Testing Strategy (ITS, Figure R.7.10-2) in ECHA Guidance R.7c (Endpoint specific guidance), all available information should be assessed before further testing for bioaccumulation is performed.

Dodecanal has a log Kow of 4.9. Therefore, a weight of evidence approach has been used to assess the bioaccumulation potential of dodecanal. Bioconcentration factors in fish have been estimated using i) three commonly used and scientifically valid QSARs and ii) in vitro metabolism data to refine the estimation of a partitioning based BCF.

Dodecanal is a non-ionic organic substance with a measured log Kow of 4.9. Therefore, it falls within the general applicability domain of all the used models. The experimentally determined high quality Log Kow value was used as an input term in the BCF estimation models.

There is evidence that dodecanal is metabolised in fish. In an in vitro metabolism assay using trout liver S9 fractions, dodecanal demonstrated a rapid metabolic turnover of 80% of the starting concentration within a 2 minute exposure period. Furthermore, dodecanal is readily biodegradable and it is generally accepted that readily biodegradable chemicals have a higher probability of being metabolised in exposed organisms to a significant extent than less biodegradable chemicals. Thus dodecanal is expected to have a lower BCF than that predicted using models that are based only on log Kow.

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. The linear model developed by Veith et al (1979) is also considered to predict maximum log BCF values. It is based on a limited data set of 56 chemicals, which are not expected to be metabolised. In addition, three chemicals from the original data set of 62 were omitted from the correlation because bioconcentration tests indicated that they bioconcentrate very little despite their comparatively large log Kow values. Since there is evidence that dodecanal is metabolised in fish, the estimated BCF values using these 3 models (3095, 3972 and 2917 L/kg respectively) are considered worst-case and unrealistic.

The BCFBAF v3.01 regression model (for non-ionic substance with a log Kow of 1.0 to 7.0) was developed from a large data set of 396 diverse chemicals. Log BCF is estimated from log Kow and a series of correction factors if applicable. These correction factors were identified on an empirical basis but, in certain cases, may be rationalised on the basis of either known biotransformation reactions or likely reactivity. The “alkyl chain (8+ -CH₂- groups)” correction factor is applied to dodecanal leading to a predicted BCF of 34 L/kg (log BCF 1.526). The use of this correction factor is supported by three compounds in the training set which share the “alkyl chain (8+ -CH2-groups)” structural feature: dodecane, 1,2-dibromodecane and 4-nonyl-phenol. All have significantly lower measured BCF values (240, 60 and 380 L/Kg respectively) compared to the predicted values (4897, 5130 and 2951 L/Kg) using the simple linear relationship between log BCF and log Kow. The BCF estimates including the correction factor (209, 214 and123 kg/L respectively) are much closer to the measured values. The BCF values for 4-Nonyl-phenol and dodecane are slightly under estimated, equivalent to a log BCF estimation error of up to 0.49. Taking this worst-case deviation into account, the predicted BCF for dodecanal was adjusted to give a conservative estimated BCF of 104 (log BCF = 2.016). 

Since there is evidence that dodecanal is metabolised in fish, model predictions (including biotransformation rates) are also considered relevant. The Arnot-Gobas method predicts the whole body primary biotransformation rate (kM) for fish using a multiple-linear regression derived equation. The prediction is considered reliable for dodecanal as it falls within the descriptor domain and structural fragment domain of the kM model. The predicted kM is converted to a kM value for the typical body size of an upper trophic, middle trophic and lower trophic fish in the respective BCF algorithms. The resulting refined BCF estimates for dodecanal are 323, 636 and 771 L/kg respectively.

The rate of substance depletion from the in vitro fish liver S9 assay was used as input into an "in vitro - in vivo" extrapolation model. The refined BCF estimates were 159 to 194.

Based on the above information, assessed together as apart of an overall WoE, it is concluded that there is no need for further investigation of aquatic bioaccumulation 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. Dodecanal has a measured log Kow of 4.9. This exceeds the CLP cut-off value of 4 and the DSD value of 3. Thus dodecanal is considered to have the potential to bioconcentrate for classification purposes. Predicted BCFs are not relevant for classification purposes.

For PBT/vPvB assessment purposes, predicted BCF estimates and log Kow may be used to provisionally assess bioaccumulation potential. Dodecanal has a measured log Kow of 4.9, which is greater than the B screening criteria of 4.5. Worst-case BCF estimates based only on log Kow are in the range of 2951 to 3095 L/kg, which is above the B definitive criterion of BCF > 2000 L/kg. However, there is evidence that dodecanal will be metabolised by fish leading to a reduced BCF. A regression QSAR corroborated with analogue data and models that take biotransformation into account gave BCF estimates in the range of 34 to 711 L/Kg, well below the REACH B-criterion of 2000 L/Kg. Thus dodecanal is considered not to have potential to bioconcentrate for PBT/vPvB assessment purposes.