Sulfonium compounds, C11-14-alkylbis(hydroxyethyl), 2-hydroxyethyl sulfates (salts)

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in sediment species, other

Remarks:

log Pow value to indicate low lipophilicity

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

The log Pow value was calculated using KOWWIN. The results clearly indicate that the lipophilicity is very low and thus this component of the test substance will not bioaccumulate in aquatic organisms.

Reference 2

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

One structure (= S+) is not present in the training set. Since the positively charged sulphure hinders uptake via biological memberanes (gills, skin, GI tract), the results of this calculation cannot be considered precise but a worst-case assumption.

Justification for type of information:

QPRF and QMRF are attached.

Principles of method if other than guideline:

Calculated with Catalogic v5.12.1 BCF base-line model v02.09.

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.09 of OASIS CATALOGIC v5.11.17

Key result

Type:

BCF

Value:

16.98 L/kg

Remarks on result:

other: logBCF corrected L/kg wet: 1.23 +- 0.49; all mitigating factors applied

Model domain similarity:

- Parametric domain: 100%

- Structural domain: 77.78% correct fragments, 22.22% fragments not present in the training chemicals

- Mechanistic domain: 100%

Effects of mitigating factors on BCF:

Acids	0.0000
Metabolism	0.770
Phenols	0.0000
Size	0.260
Water solubility	9.38E-005

Diameter information (values are given in Angstrom):

DiamMax Min value = 11.776 Å

DiamMax Max value = 20.402 Å

DiamMax Average = 16.585 Å

Reference 3

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

One structure (= S+) is not present in the training set. Since the positively charged sulphure hinders uptake via biological memberanes (gills, skin, GI tract), the results of this calculation cannot be considered precise but a worst-case assumption.

Justification for type of information:

QPRF and QMRF are attached.

Principles of method if other than guideline:

Calculated with Catalogic v5.12.1 BCF base-line model v02.09.

Specific details on test material used for the study:

CCCCCCCCCCCCCCS[+](CCO)CCO

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF base-line model v02.09 of OASIS CATALOGIC v5.11.17

Key result

Type:

BCF

Value:

36.31 L/kg

Remarks on result:

other: logBCF corrected L/kg wet: 1.56 +- 0.61; all mitigating factors applied

Model domain similarity:

- Parametric domain: 100%

- Structural domain: 80.95% correct fragments, 19.05% fragments not present in the training chemicals

- Mechanistic domain: 100%

Relative effects of mitigating factors on BCF:

Acids	0.0000
Metabolism	0.711
Phenols	0.0000
Size	0.308
Water solubility	1.646E-005

Diameter information (values are given in Angstrom):

DiamMax Min value = 13.945 Å

DiamMax Max value = 24.223 Å

DiamMax Average = 18.018 Å

Description of key information

Significant accumulation in organisms is not to be expected.

Additional information

No experimental data is available on the bioaccumulation potential of Sulfonium compounds, C11-14-alkylbis(hydroxyethyl), 2-hydroxyethyl sulfates (salts). Therefore, all available related data is combined in a Weight of Evidence (WoE), which is in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2, to cover the data requirements of Regulation (EC) No. 1907/2007 Annex IX and X (ECHA guidance section R.7.11.5.3, page 121). Due to available information based on the structure of the substance the performance of an animal test is not considered to be necessary to assess its bioaccumulation potential in a conservative way. This information comprises the metabolism of the components of the test substance and QSAR calculations combined in a Weight-of- evidence approach.

 

Bioaccumulation via aqueous exposure

Sulfonium compounds, C11-14-alkylbis(hydroxyethyl), 2-hydroxyethyl sulfates (salts) is well miscible in water (~ 1000 mg/L at 25 °C) and can be judged as readily biodegradable. According to the Guidance on information requirements and chemical safety assessment, Chapter R.7b, readily biodegradable substances can be expected to undergo rapid and ultimate degradation in most environments, including biological Sewage Treatment Plants (STPs) (ECHA, 2012a). In addition, the substance tends to adsorb to activated sludge. Therefore, after passing through conventional STPs, only a very low concentration of the test substance is likely to be (if at all) released into the environment. Considering this, one can assume that the availability of the substances in the aquatic environment will be extremely low, which reduces the probability of adsorption and uptake from the surrounding medium into organisms (e.g., see Björk 1995, Haitzer et al. 1998). In addition, being surfactant and positively charged the substance will quickly adsorb to organic and inorganic surfaces in the environment, which further reduces the uptake from the surrounding medium into organisms.

A log Pow is not available, as the main components of the substance are both surface active and a salt. However, the partition coefficient of 2-hydroxyethyl sulfate (calculated log Pow = -4.7) indicate that this component is not bioaccumulative only due to its low lipophilicity.

If environmental concentrations facilitate exposure, the ionic nature (strong polar head group due to positive charge) and the surface-active properties of the organic salt will drastically hinder the uptake of the sulfonium compounds from medium into organisms via crossing biological membranes (gill, skin, GI tract)as it its general agreement that such substances do not readily diffuse across biological membranes(e.g., see Heerklotz 2008).

Since the substance will to some degree bind to particulate organic matter, the main route of exposure for aquatic organisms such as fish will be via food ingestion or contact with suspended solids:

 

Bioaccumulation via oral uptake

The accumulation of a substance in an organism is determined, not only by uptake, but also by distribution, metabolism and excretion. Accumulation takes place if the uptake rate is faster than the subsequent metabolism and/or excretion. Within the fluids of the gastrointestinal (GI) tract, the chemical will be present in its ionized form. It is common understanding that ionic and surface-active substances do not readily diffuse across the walls of the GI tract. However, absorption properties may be enhanced following micellular solubilization by bile salts and hydrolysis reactions and thus passing through aqueous pores or membranes with bulk transport of water cannot per se be excluded. The findings observed in a combined repeated dose toxicity study with the reproduction and developmental toxicity screening test (OECD 422) in rats support the assumption that at least fractions of the UVCB substance become bioavailable following oral exposure. Here the UVCB substance was orally administered at dose levels of 0, 30, 100 and 300 mg/kg bw/day. Besides local effects on the GI tract and resultant weight loss, systemic effects on the adrenal glands (hypertrophy) and on the thymus (lymphoid atrophy) were noted at dose levels of 100 and 300 mg/kg bw/day. The reproductive ability of males and females remained undisturbed at any dose level. The ready biodegradability also supports the assumption that the substance or degradation products will be taken up by organisms to a certain degree.

Absorbed fractions of the test substance are considered to be bio-transformed within the body by Phase I enzymes while undergoing functionalization reactions aiming to further increase the hydrophilicity. In addition, Phase II conjugation reactions may covalently link an endogenous substrate to the absorbed chemicals or the respective Phase I metabolites to ultimately facilitate excretion. However, being already well soluble sulfonium ions are also considered to be excreted directly. Several investigations showing the formation of sulfonium ions by methylation of thioethers using methyltransferases as important step to make thioethers more water-soluble sulfonium and thus suitable for urinary excretion (e.g., Mozier and Hoffman 1990).

Absorbed sulphate is used for further biotransformation reactions, such as to form cysteine, methionine, and other metabolites (via reduction to sulfide) and can be biosynthetically incorporated into other macromolecules such as glycoproteins, glycosaminoglycans, and glycolipids (e.g., Leustek 2002, Morris and Sagawa 2000). In addition, sulphates, in unbound form or as conjugates of various substances, can be eliminated from the body via excretion with the urine. Fractions of the UVCB substance which are not absorbed within the GI tract are readily excreted with the faeces.

These assumptions of slow uptake and rapid metabolism are supported and verified by QSAR calculations performed for a Sulfonium, C11 bis(hydroxyethyl)and a Sulfonium, C11 bis(hydroxyethyl) ion using the BCF base-line model v02.09 from Oasis Catalogic v5.12.1. BCF values were calculated to be in the range of 16 – 37 and showed metabolism as main mitigating factor. Although the substances not completely fall into the applicability domain of the tool (sulphur structure is not known from the training set), the results can be interpreted as worst-case assumptions, since (i) the more lipophilic components of the substances are considered and (ii) the uptake reducing sulfonium ion is not considered in the calculation. The results confirm that uptake into organisms is rather low and the metabolism of the substance if taken up by organisms very distinct.

In addition, the low bioaccumulation potential calculated for the substance is supported by the fact that long-term toxicity tests show effect values in the same range than the acute toxicity tests (e.g., Acute chronic ratio (ACR) Daphnia = 0.72; ACR algae = 2) indicating (a) narcotic and physical effects based on the positive charge as most probable mechanism of action and (b) no increasing concentrations of the test substance in aquatic organisms over time.

 

Based on these data the bioaccumulation of Sulfonium compounds, C11-14-alkylbis(hydroxyethyl), 2-hydroxyethyl sulfates in aquatic organisms is considered to be negligible. The main route of exposure will be via oral uptake. Based on slow uptake and rapid metabolism of sulfonium compounds, it is reasonable to conclude that bioaccumulation of the substance is unlikely to occur. Therefore, and due to animal welfare reasons, no confirmatory animal test according to OECD 305 is deemed necessary.

Furthermore, being cationic, surface active and rapidly metabolizable, it is highly questionable if it would be even possible to perform a meaningful experimental bioaccumulation study with the test substance. A proper quantification is considered to be extremely error-prone since (i) test substance will be adsorbed at the outer surface and gills of fish, (ii) potentially radiolabeled molecules will partly be incorporated in biomass due to metabolic processes, and (iii) quantification of a UVCB is in general very difficult.

 

References

Björk M. 1995. Bioavailability and uptake of hydrophobic organic contaminants in bivalve filter-feeders. Ann Zool Fenn 32(2): 237-245

ECHA. 2012a. Guidance on information requirements and chemical safety assessment, Chapter R.7b: Endpoint specific guidance, version 2.2 (August 2013), Helsinki, Finland

Haitzer M et al. 1998. Effects of dissolved organic matter (DOM) on the bioconcentration of organic chemicals in aquatic organisms: a review. Chemosphere 37(7): 1335-1362

Heerklotz H. 2008. Interactions of surfactants with lipid membranes. Q Rev Biophys 41(3-4): 205-264

Leustek T. 2002. Sulfate metabolism. Arabidopsis Book1: e0017

Morris M.E, Levy G. 1983. Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate. Clinical Pharmacolgy and Therapeutics 33: 529-536

Morris M.E., Sagawa K. 2000. Molecular mechanisms of renal sulfate regulation. CRC Critical Reviews in Clinical Laboratory Medicine 37(4): 345-388.

Mozier NM, Hoffman JL. 1990.Biosynthesis and urinary excretion of methyl sulfonium derivatives of the sulfur mustard analog, 2-chloroethyl ethyl sulfide, and other thioethers. Faseb J 4(15): 3329-3333.