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Administrative data

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Description of key information

Absorption: > 75% via the GI tract
Distribution: ca. 1% in the liver and < 1% in the kidney
Metabolism: Degradation of the ether linkage and oxidation of the alkyl chain to form ultimately carbon dioxide and water.
Excretion: The majority was excreted via urine and faeces depending on amount of EO units, minor portions in expired CO2. Metabolism of longer alkyl chains giving rise to a higher percentage of 14CO2 into expired air, and a lower percentage in urine.
Assumed dermal absorption: 2%

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
75
Absorption rate - dermal (%):
2

Additional information

Summary:

100% of the 14C-labelled alcohol ethoxylates are assumed to be absorbed via the gastrointestinal tract after oral ingestion. The majority of the absorbed dose is rapidly excreted via urine and and faeces and minor parts via expired CO2 with more of the AE being excreted via the faeces and expired in air as the ethoxy unit length increased. Moreover, the length of the alkyl chain is assumed to have an impact on AE with longer alkyl chains being excreted at a higher proportion into expired air and less into the urine and faeces.

A maximum of 1% of the administered dose was found in liver and kidneys, respectively.

Metabolisation is shown to be rapid and complete, the most likely pathway of AE metabolism being the hydrolysis of the ether linkage and subsequent oxidation of the alkyl chain to form lower molecular weight polyethylene glycol-like materials and ultimately carbon dioxide and water.

Only minor amounts of the AEs are directly absorbed via the skin (2%).

 

Oral absorption, distribution, metabolism and excretion of three 14C-labelled alcohol ethoxylates (i.e., C12AE3, C12AE6 and C12AE10) were determined in female Wistar rats. The tracer was located in the alkyl chain without any further specification. Following administration, the rats were placed in a metabolism chamber for 4 days and the faeces, urine and air were monitored for 14C activity. At the end of the period, the study was terminated and various tissues and organs were removed and analysed for radioactivity. In summary, 14C was excreted by the rats mainly in the urine after oral or parental administration of the compound. The relative proportions of compounds found in the urine, faeces, air and carcass did not differ with the route of application and the recoveries were close to 100% for all routes. Small proportions were recovered as 14CO2 and in the faeces. These proportions increased with longer ethoxylate length. The results suggest an almost complete absorption from the alimentary tract. There were indications that some of the longer ethoxylate chain compounds may be excreted via the bile or excreted into the intestine by other routes. Each detergent gave rise to two distinct polar metabolites in the urine and no parent compound. It was hypothesized that the alcohol chain was oxidized and the ethoxylate residue remained intact.

In another study, the elimination and resorption of 14C labelled C14-18AE10 was monitored over 72 hours after a single oral gavage application at doses of 20, 40, 100, 200, 500 and 1000 mg/kg bw to Wistar rats. From the 40, 200 and 1000 mg/kg bw dose group (i.e., four male rats) one animal was placed in a closed metabolism cage to monitor exhaled 14CO2 whereas the other rats were kept in a non-closed system. Urine and faeces were monitored daily over 4 days and gastrointestinal tract, liver, oesophagus, kidney and blood were monitored for 14C activity. Most of the administered compound was resorbed in the intestine (i.e., about 80-90%) of that approx. 30% was excreted via the bile and 2% was excreted as 14CO2 in air. Within 72 hours about 98-99% of the compound was rapidly eliminated with 90% being excreted within the first 24 h. The test compound was excreted in the urine and in the faeces (i.e., about 40-50%) to equal amounts. Very low levels of residual radioactivity (i.e., about 1%) were noted in the liver and to an even lower extent in the kidney. No dose-dependant differences in elimination were observed. The test substance was excreted rapidly even at quite high doses. The highest dose did not cause any symptoms of toxicity within the test rats. 14C-labelled C12-15AE6 and C12-15AE7 were applied orally to rats to evaluate the intake (absorption) and excretion in rats. The label was either in the hydroxylbearing carbon or the α-carbon of the alkyl group. The orally dosed material was absorbed quickly and extensively (> 75% of the dose). In most of the experiments about half of the 14C was excreted promptly in the urine; smaller amounts appeared in the faeces and CO2. Much of the 14C in the faeces probably resulted from biliary excretion.

The mammalian absorption, distribution and excretion of AE containing linear and branched carbon chains were comparable. When rats were administered C12AE6 (linear), C13AE6 (branched) and C15AE7 (branched) the distribution in the rat was similar with the major portion of the radioactivity appearing in the urine (52-55%) and smaller amounts in the faeces (23-27%) and expired CO2 (2-3%) for all three compounds.

In another study with volunteers the absorption, distribution and excretion of 14C labelled C12AE6 (linear) and C13AE6 (branched) was examined in human males given a capsule with the surfactants. The behaviour of the two compounds in the males was comparable and most of the radioactivity was recovered after 24 hours in the urine, 75% for both compounds.

The biggest structural component determining the absorption, distribution and excretion of AE was therefore not the degree of branching of the alcohol but rather the length of the ethoxy chain unit with more of the AE being excreted via the faeces and expired in air as the ethoxy unit length increased. Also, the length of the alkyl chain may have determined how AE were distributed in the rat. An oral gavage study with 14C labelled C14-18AE10 (linear) indicated that AE with longer alkyl chains were excreted at a higher proportion into expired air and less into the urine and faeces (i.e., about 40-50%).

The major degradation pathway of AE appears to be the degradation of the ether linkage and oxidation of the alkyl chain to form lower molecular weight polyethylene glycol-like materials. By degradation of the ether linkage and oxidation of the alkyl chain, fatty acids will be produced next to the polyethylene glycol-like materials. These ultimately yield in carbon dioxide and water. Studies with radio-labelled compounds showed that both the alkyl and the ethoxy groups are sites of attack. Thus, also the polyethylen glycol like materials will be degraded to various C-chain length. AE surfactants labelled either with 14C in the α-carbon of the alkyl group or the hydroxyl-bearing position of the ethoxylate moiety showed that distribution and excretion of ethoxylate groups of varying length was similar but the metabolism of their alkyl chains was a function of chain length. Metabolism of the alkyl chain seemed to change as the alkyl chain length increased with longer alkyl chains giving rise to a higher percentage of 14CO2 into expired air, and a lower percentage in urine.

 

The dermal penetration rate for alcohol ethoxylates was calculated on the basis of a dermal penetration study with 14C-labelled C12AE6 in two human volunteers calculated according to the following algorithm:

Kp = dermal flux / exposure time x concentration of test solution;

Kp = 0.022 mg/cm²/(24 hours x 100 mg/cm³) = 0.0000092 cm/h.

This penetration rate is derived from measured data and assumes - conservatively - 2% absorption within the first 24 hours following dermal application. In the study, however, the maximum systemically available C12AE6 after 144 hours exposure was determined to be 1.82%. It should be noted that the study was performed only on few test subjects and that reporting was limited. However, the study clearly demonstrated that AE penetrate poorly through human skin and clearly less readily than through rat skin. The human study was therefore judged to represent more reliably the systemic availability of AE in humans following dermal exposures to AE containing cleaning products. It should also be noted that rat studies (HERA, 2009) have shown that short chain AE (C8-C14 and E3-E7) penetrate the skin more readily than longer chained AE (i.e., >C14, >E7). Thus, calculating dermal exposures to the whole range of AE on the basis of a dermal penetration rate derived from a short chain AE such as C12AE6 can be considered as a conservative scenario.