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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Remarks:
The result was obtained by the valid application of a well-established predictive method.
Justification for type of information:
QSAR prediction: refer to attached Environmental Fate Category Report and Bioconcentration Position Paper.
Principles of method if other than guideline:
The result was obtained using SRC BCFBAF v4.01 program.
Type:
BCF
Value:
67 L/kg
Remarks on result:
other: (log Kow regression-based estimate)
Type:
BCF
Value:
>= 510 - <= 750 L/kg
Remarks on result:
other: (Arnot-Gobas method including biotransformation rate estimates)
Conclusions:
A BCF value of 67 (log Kow-based regression) and 510 -750 (Arnot-Gobas method incorporating metabolic transformation) has been calculated using SRC BCFBAF v4.01 (2010). These considerations suggest that it is unlikely that bioaccumulation would be exhibited in nature.  The result is considered to be reliable.
Endpoint:
bioaccumulation in aquatic species: fish
Remarks:
Biotransformation in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH
The hypothesis is that the category members have similar structures and properties (low bioaccumulation potential, with metabolism and bio-transformation in vivo), which are consistent across the category (Scenario 6 in the RAAF). The consistency of this property across the category is discussed in the endpoint summary.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the test material identity information within each endpoint study record and to the endpoint summary. The source chemicals and the target chemical are linear aliphatic alcohols which are members of the long chain linear aliphatic alcohol Category.

The long chain linear aliphatic alcohol Category has at its centre an homologous series of increasing carbon chain length alcohols. The category members are structurally very similar. They are all primary aliphatic alcohols with no other functional groups. The category members are linear or contain a single short-chain side-branch at the 2-position in the alkyl chain, which does not significantly affect the properties (‘essentially linear’). The category members have saturated alkyl chains or contain a small proportion of naturally-occurring unsaturation(s) which does not significantly affect the properties. The branched and unsaturated structures are considered to have such similar properties that their inclusion in the category is well justified.
Impurities: Linear and/or ‘essentially linear’ long chain aliphatic alcohols of other chain lengths may be present. These are not expected to contribute significantly to the properties in respect of this endpoint due to consistent properties (see point 3).
There are no impurities present at or above 1% which are not category members or which would affect the properties of the substance.

3. CATEGORY JUSTIFICATION
The category members are structurally very similar (see point 2) and are biochemically very similar. The metabolic synthesis and degradation pathways are well established. This Category is associated with a consistency and predictability in the physicochemical, environmental, and toxicological property data across its members.

The consistency of observations in this property across the range of chain lengths covered by this Category is described in the Endpoint Summary and in the Category Report attached in Section 13.

In this registration, information on metabolism in vivo in fish is available based on read-across from a member of the category with longer chain length, providing evidence that even a relatively lipophilic category member substance is very rapidly biotransformed.

4. DATA MATRIX
A data matrix for the C6-24 alcohols Category is attached in Section 13.
Reason / purpose:
read-across source
Type:
other: Fate of fatty alcohol over 72 hours following oral exposure
Basis:
other: Expected distribution of residues in a range of tissue types
Remarks on result:
other: Overall, approx 3% expected to remain as free fatty alcohol 72 hours after oral exposure to alcohol (remainder expected to be converted to metabolites).

Description of key information

Key value for chemical safety assessment

BCF (aquatic species):
750 L/kg ww

Additional information

No reliable guideline-standard measured bioconcentration studies are available for dodecan-1-ol. In accordance with Section 2 of REACH Annex XI, the study does not need to be conducted because guideline-standard studies of bioaccumulation in fish would be confounded by the technical difficulties of maintaining the test substance in solution. As was demonstrated in the long-term studies of effects of close structural analogues in invertebrates (see Section 6.1.4), severe difficulties were encountered in conducting the study due to the finding that biodegradation (including metabolism) of the test substances in the test system was almost complete within the 24 h test media renewal period. Similarly, the long-term study in fish conducted with the structurally analogous alcohol decan-1-ol required substantial method development work to overcome severe difficulties maintaining the test substance in the test system (see Section 6.1.2).

There is no requirement in REACH to conduct any secondary poisoning assessment, in view of the consistent lack of systemic toxic effects of the alcohols across this category to mammals. In addition, the rapid biodegradation of the substance, combined with evidence of rapid metabolism in fish, mammals and micro-organisms (see Mankura et al. 1987) on oleyl alcohol (z-octadec-9-enol, CAS 148-28-2), and see Sections 7.1, 6.1.4), suggest that it is unlikely that bioaccumulation would be seen in studies.

A BCF value of 67 has been calculated using SRC BCFBAF v3.01 (2012). This model uses a log Kow-based equation with modified algorithms for specific structural features. This version of the software also incorporates for the first time a modification for biotransformationin vivo, producing BCF values ranging between 510-750 for lower and upper trophic levels. These considerations suggest that it is unlikely that bioaccumulation would be exhibited in nature. 

Another estimated BCF value of 3801 L/kg has been reported for dodecan-1-ol from the Danish Environmental Protection Agency in 1993 which is considerably higher than the modelled result using the BCFBAF QSAR model. As no guideline was followed and no other information is reported, this value is considered outdated and therefore the study is disregarded.

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

All the reviewed data indicate that log Kow-based QSARs overestimate BCF because they take no account of biotransformation and metabolism of alcohols by a wide range of biota from bacteria to mammals (Veenstraet al.,2009; Mudge, 2008). These observations have recently been critically assessed using cellular biotransformation assays of ethoxylated alcohols and other aliphatic surfactants which confirm that metabolism of the alkyl chain can lower BCF by orders of magnitude (Dyeret al.,2008; Cowan-Ellsberryet al., 2008). For the more soluble chain lengths, evaluated in non-guideline BCF studies on linear alcohols and guideline studies for branched alcohols, predicted BCFs are overestimated by at least an order of magnitude (Fisket al., 2012).  

Values predicted for 2-methyl branched alcohols are fairly consistent with the predicted values for the linear structures of the same carbon number based on BCFBAF v3.01 estimates, with small variations only associated with small margins of variation in the log Kow value. The presence of branched constituents is therefore not expected to significantly affect the predicted values; multiply-branched alcohols have been demonstrated to be metabolised ca. 2.5 times less efficiently by pig liver enzyme homogenate than linear structures of the same carbon number (Menzelet al., 2001, in which different isomeric forms of C12 saturated alcohols were studied as well as C14 linear alcohol), but a single branch is unlikely to have a significant impact.  

For the multi-constituent/UVCB long chain alcohols, a single BCF value is difficult to predict. However, the values for the constituents present are relevant.   There is ample experimentalin vivoevidence of metabolism in various trophic levels. Rapid biotransformation into tissue lipids has been demonstrated by Mankura et al. 1987 in fish (carp), for oleyl alcohol (C18, unsaturated). Biotransformation of linear structures has been demonstrated to be faster than for multiply-branched structures (Menzelet al., 2001) in accordance with expectations based upon the metabolic pathways. Predicted bioconcentration factors, using methods which take account of the expected metabolism in vivo, estimate low BCF values. Experimental studies using structural analogues show low BCF values. All linear alcohols in this chain length range are readily biodegradable in reliable standard studies.  

BCF can be calculated using SRC BCFBAF v3.01 (2012). This model uses a log Kow-based equation with modified algorithms for specific structural features. This version of the software also incorporates for the first time a modification for biotransformation in vivo. These considerations suggest that it is unlikely that bioaccumulation would be exhibited in nature for alcohols in the C6-24 linear and essentially-linear alcohols category. 

It is therefore concluded that the long-chain alcohols in this category are non-bioaccumulative. This conclusion is considered to be sufficiently well-supported to justify no need for further testing in fish, since vertebrate testing for the purposes of REACH registration should be avoided where adequate existing evidence exists, and in view of the expected severe technical difficulties in conducting such a test.

Further information can be found in the attached position paper.

References:

Cowan-Ellsberry, C.E., Dyer, S.D., Erhardt, S., Bernhard, M.J., Roe, A.L., Dowty, M.E., Weisbrod, A.V., 2008. Approach for extrapolating in vitro metabolism data to refine bioconcentration factor estimates. Chemosphere 70, 1804–1817.

Dyer, S.D., Bernhard, M.J., Cowan-Ellsberry, C., Perdu-Durand, E., Demmerle, S., Cravedi, J.-P., 2008. In vitro biotransformation of surfactants in fish. Part I: Linear alkylbenzene sulfonate (C12-LAS) and alcohol ethoxylate (C13EO8). Chemosphere 72, 850–862.

Peter Fisk Associates Limited (2012) Position paper: Bioaccumulation of Aliphatic Alcohols in the context of REACH registration. Reference: PFA.197.018.002. Date: 10 August 2012.