Alcohols, C12-18, ethoxylated, sulfates, sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Expert judgement combined with experimental data. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference

Reference Type:

publication

Title:

HERA report on Alcohol Ethoxysulphates.

Author:

A.I.S.E. and Cefic

Year:

2003

Bibliographic source:

http://www.heraproject.com/files/1-HH-04-HERA AES HH web wd.pdf

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

No guideline exists for this type of appraisal.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Category of alcohol ethoxysulphates

IUPAC Name:

Category of alcohol ethoxysulphates

Details on test material:

not applicable

Radiolabelling:

yes

Test animals

Species:

other: rat and human

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: oral, i.p., i.v.

Duration and frequency of treatment / exposure:

Various

Doses / concentrations

Remarks:

Doses / Concentrations:
Various

No. of animals per sex per dose / concentration:

Various, for details see "executive summary"

Control animals:

other: Various, for details see "executive summary"

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Various, for details see "executive summary"

Details on distribution in tissues:

Various, for details see "executive summary"

Details on excretion:

Various, for details see "executive summary"

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Various

Any other information on results incl. tables

Various, for details see "executive summary"

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Following oral exposure, AES is readily absorbed in the gastrointestinal tract in man and rat and excreted principally via the urine. The length of the ethoxylate portion in an AES molecule seems to have an important impact on the biokinetics of AES in humans and in the rat. Alcohol ethoxysulfates with longer ethoxylate chains (>7-9 EO units) are excreted at a higher proportion in the faeces. Once absorbed, AES is extensively metabolized by beta- or omega oxidation.

Executive summary:

McDermott et al. (1975) studied the absorption of C₁₆AE₃S and C₁₆AE₉S, labelled with¹⁴C in the 1-position of the alkyl chain, after oral exposure in man and rats. Seventy-two hours after administration of C₁₆AE₃S, radioactive material was mainly excreted via urine (man: 80%; rat: 50%) and to a lesser extent via faeces (man: 9%; rat: 26%) and air (man: 7%; rat: 12%). For C₁₆AE₉S however, the radioactivity was mainly excreted via faeces (man: 75%; rat: 82%) and to a lesser extend via urine (man: 4%; rat: 0.6%) and air (man: 6%; rat: 4%). The length of the ethoxylate portion of an AES molecule appears to determine the metabolic fate of the compound following oral administration in both man and rat. There was no evidence of hydrolysis of the sulphate group or of metabolism of the ethoxylate portion of the molecule. The major metabolite found in urine had the following structure:^-OOCCH₂(OCH₂CH₂)_xOSO₃^-where x equals either 3 or 9, respectively.

In a similar investigation, Taylor et al. (1978) studied the metabolic fate of orally, intraperitoneally or intravenously administered¹⁴C-C₁₁AE₃S and¹⁴C-C₁₂AE₃S in the rat. The authors observed that both compounds were extensively metabolized (ω-, β-oxidation) with the proportion of radioactivity appearing in urine and respired air generally independent of the route of administration. Some sex differences in the proportions of radioactivity excreted in urine and respired air was seen, but total recoveries for both compounds were comparable. By the oral route, 67% of the administered radioactivity with C₁₁AE₃S appeared in the urine of male rats compared to 45% in females; expired air contained 19% and 35% of administered radioactivity respectively; 4-5% was present in faeces for both sexes. The major urinary metabolite of C₁₂AE₃S was identified as 2-(triethoxy sulfate) acetic acid, with C₁₁AE₃S, the major urinary metabolite was tentatively identified as 3-(triethoxysulfate) propionic acid.

 

Conclusion:

Following oral exposure, AES is readily absorbed in the gastrointestinal tract in man and rat and excreted principally via the urine. The length of the ethoxylate portion in an AES molecule seems to have an important impact on the biokinetics of AES in humans and in the rat. Alcohol ethoxysulfates with longer ethoxylate chains (>7-9 EO units) are excreted at a higher proportion in the faeces. Once absorbed, AES is extensively metabolized by beta- or omega oxidation.