Alcohols, C16-18, ethoxylated, phosphates

Endpoint summary

Description of key information

Alcohols, C16-18, ethoxylated, phosphates is supposed to be well absorbed by the oral and inhalation route. Dermal absorption is rather low. Alcohols, C16-18, ethoxylated, phosphates is expected to be degraded in a first step to the long-chain alcohols, ethoxylated glycol, and phosphate. The degradation products are further metabolised by oxidation (long-chain alcohols, ethoxylated glycol) and are utilised in intrinsic pathways. No accumulation is expected. Excretion of the polyethoxylated glycols occurrs via urine or faeces, depending on the grade of ethoxylation.

Additional information

In accordance with Annex VIII, Column 1, Item 8.8 of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behaviour of the substance Alcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4) was conducted to the extent that can be derived from the relevant available information on physicochemical and toxicological characteristics. There are no studies evaluating the toxicokinetic properties of the substance available.

Absorption

Absorption is a function of the potential of a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012).

Oral

After oral ingestion, Alcohols, C16-18, ethoxylated, phosphates and other substances of this class are supposed to be well absorbed (summarized in EPA, 2009). Based on the physico-chemical properties absorption of the monoester is possible due to the low molecular weight < 500 g/mol. The diester may be too big for absorption based on the molecular weight of >500 g/mol. Due to the low water solubility (< 1 mg/L) and the log Pow of > 6 absorption may be due to micellar solubilisation or passive diffusion. In addition, the absorption may be enhanced due to the surfactant properties of Alcohols, C16-18, ethoxylated, phosphates, provoking damage to cell membranes.

Based on information from structurally similar substances as alcohol ethoxysulphates (AES), oral absorption is mainly dependent on the length of the polyoxyethylene moiety (POE; summarized in HERA, 2003). AES with an alkyl chain length of 16 and with POE n = 3 are readily absorbed, whereas the alkyl chain length of 16 in combination with POE n = 9 led to poor absorption.

Dermal

There are no data available on dermal absorption or on acute dermal toxicity of Alcohols, C16-18, ethoxylated, phosphates. On the basis of the following considerations, the dermal absorption of Alcohols, C16-18, ethoxylated, phosphates is considered to be low. Regarding the octanol/water partition coefficient of > 6 in combination with the low water solubility and the fact that the molecule is ionic, a low dermal absorption rate is anticipated based on expert judgement.

In addition, data with Alcohol ethoxysulphates, which are structural similar to the phosphates and possess similar physico-chemical properties, show that dermal absorption is rather low. For risk assessment 5% dermal absorption was proposed as an upper bond using a conservative approach (EPA, 2009). Data from studies in rats gave a dermal absorption of 0.0163 µg/cm²/h for an Alcohol ethoxysulphate (C12, POE = 3; Taylor et al., 1978).

Inhalation

The test substance has a very low vapour pressure < 0.01 Pa at 25 °C thus being of low volatility. Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not significant.

However, the substance may be available for respiratory absorption in the lung after inhalation of aerosols, if the formulated substance is sprayed. In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract (ECHA, 2012).

As discussed above, absorption of the parent substance after oral administration is expected based on the physico-chemical properties of the substance. Thus, absorption after inhalation cannot be excluded if the test substance reaches the alveolar region, as the mechanism of absorption may be similar to the oral route.

As the oral absorption is expected to be high, inhalative absorption of the test substance is considered to be not higher than through the intestinal epithelium.

Distribution, metabolism and excretion

Distribution of a compound within the body depends on the physicochemical properties of the substance especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2012).

Alcohols, C16-18, ethoxylated, phosphates (monoester) is expected to be hydrolysed to alcohols, polyalkoxylate glycols and phosphate. These constituents are expected to be further metabolised and/or be excreted rapidly. The polyalkoxylate glycols and phosphates are widely distributed within the water compartment of the body (summarised in EPA, 2009). The alcohols are further metabolized in intrinsic pathways via α-, β-, or ω-oxidation in mitochondria (OECD, 2006). The emerging phosphate will be part of the intrinsic phosphate pool and can be used in several intrinsic pathways (ATP synthesis; creation of bone mineral) or is excreted via urine (Lehninger, 1970). Because of the metabolism of the alcohols and phosphate no accumulation is expected.

As for the monoester, for the diester, the hydrolysis to the alcohols is supposed to be the first step of metabolism (EPA, 2009), although steric hindrance could result in a lower alcohol hydrolysis. The remaining ethoxylated phosphate is supposed to be excreted as such via the urine. Further oxidative metabolism of the polyethoxy moiety cannot be excluded. Dephosphorylation will probably not take place, due to lacking unspecific diesterase activity in humans. The ubiquitous occurring enzymes alkaline and acid phosphatases only possess monoesterase activity. 

The AE used as source substances are expected to be hydrolysed to alcohols and polyalkoxylate glycols and are further metabolised and/or be excreted rapidly. The mammalian metabolism of AE is highly efficient and involves oxidation to carboxylic acids and subsequent elimination of C2 units in the mitochondrial beta oxidation process.

Excretion of the polyalkoxylate glycols (POE = 3) is expected to occur mainly via urine (summarized in HERA, 2009). Excretion depends on the grade of polyethoxylation. Polyalkoxylate glycols with POE = 3 are excreted mainly via urine (approximately 80%), whereas an increase of POE grade leads to an increase of amount excreted via faeces and expired air. A polyalkoxylate glycol (C12, with POE = 10) was excreted via urine (49.8%), faeces (17.4%), and expired air (12.4%). 4.5% were detected in the carcass. Whereas a polyalkoxylate glycol (C12, with POE = 3) was excreted via urine (78.3%), faeces (6.9%), and expired air (6.5%). 2.5% were detected in the carcass.