Alcohols, C9-11-branched and linear

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key 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. Reliability 2

Justification for type of information:

QSAR prediction: refer to attached report Bioaccumulation assessment for linear, unsaturated and branched alcohols and attached QPRF.

Principles of method if other than guideline:

The result was estimated by the CATALOGIC BCF baseline model program with adjustment for metabolism and size.

Type:

BCF

Value:

26 L/kg

Conclusions:

A BCF value of 26 was obtained by use of an accepted property prediction tool. The result is considered to be reliable.

Description of key information

Bioconcentration factor in fish: low (BCF 26 L/kg), estimated by QSAR. The bioconcentration factor (adjusted for bioavailability limitations, rapidin vivometabolism and transformation, and excretion processes) was estimated by CATALOGIC BCF base-line model (version 03.10). Based on this, the substance is non-bioaccumulative.

Key value for chemical safety assessment

BCF (aquatic species):

26 L/kg ww

Additional information

No reliable guideline-standard measured bioconcentration studies are available for decan-1-ol.

Reliable and validated QSAR predictions of bioconcentration in fish (adjusted for the mitigating effects of bioavailability limitations, rapidin vivometabolism and transformation, and excretion processes), are available for this substance and its structural analogues in the Alcohols Category, suggesting low values and consistent trends. The predicted values are reliable and are suitable as Key data for the REACH registrations of these substances.

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 in invertebrates (see Section 6.1.4), severe difficulties were encountered in conducting the study due to biodegradation (including metabolism) of the test substance in the test system was almost complete within the 24 h test media renewal period. Similarly the long-term study in fish 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 (Mankura et al. 1987), and see Sections 7.1, 6.1.4), suggest that it is unlikely that bioaccumulation would be seen in studies.

A BCF value of 26 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 a modification for biotransformationin vivo. This is taken as supporting data (based on an understanding that the training and validation underlying the CATALOGIC approach are more robust).

These considerations suggest that it is highly unlikely that this substance would bioaccumulate in biota. Validated quantitative QSAR predictions of BCF are available, which are sufficient for the needs of the REACH chemical safety assessment. The registrants do not propose to attempt a bioconcentration study following OECD Guideline 305.

 

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

The bioconcentration predictions of alcohols in the range C6-24 (linear, essentially-linear, and unsaturated structural types) were based on their lipophilicity, and have been adjusted for the effect of metabolism and the molecular size as mitigating factors. The substances are not ionisable (i.e. no effect of ionisation is expected) and the effect of water solubility is negligible. Of the predicted first level metabolic reactions for linear, essentially linear and unsaturated alcohol structures relevant to this Category, those which reduce the maximum bioaccumulation potential (i.e. BCFMAX) significantly are: oxidation of alcohol group to aldehyde; O-glucuronidation; ¿-oxidation and epoxidation. Based on these reactions the starting alcohols are practically eliminated after the first level metabolism. The predicted second and third level metabolic reactions are oxidation of alcohol group to aldehyde; oxidation of aldehyde group to carboxylic acid; ß-oxidation and O-glucuronidation (OASIS-LMC, 2019). The CATALOGIC BCF base-line model takes into account the simulated first level metabolism.

This is consistent with previous evaluations which concluded that more simplistic 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 (Veenstra et al., 2009; Mudge, 2008). These observations have 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 (Dyer et al., 2008; Cowan-Ellsberry et 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 (Fisk et al., 2012).

The expectation of rapid metabolism and biotransformationin vivois also consistent with the rapid biodegradation of the substance, evidence of rapid metabolism in fish, mammals and micro-organisms (Mankura et al. 1987), and see Sections 7.1 and 6.1.4).

BCF values estimated by the CATALOGIC model for 2-methyl and 2-ethyl branched isomeric alcohols are very close to the estimated values for the linear structures of the same carbon number. The presence of branched constituents as impurities is therefore not expected to significantly affect the predicted values. Alcohol isomers with multiple alkyl side-branches 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 (Menzel et 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.

The BCF value estimated by the CATALOGIC model for the unsaturated alcohol (z)-octadec-9-enol is close to the estimated value for the linear saturated structure of the same carbon number.

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 experimental in vivo evidence 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 (Menzel et al., 2001) in accordance with expectations based upon the metabolic pathways. All linear alcohols in this chain length range are readily biodegradable in reliable standard studies.

It is therefore concluded that all of 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 performance of such a test.

References:

Oasis-LMC. Bioaccumulation assessment for linear, unsaturated and branched alcohols (unpublished study). 26 July 2019

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.