Alcohols, C6-8, ethoxylated

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-Across of experimental data from analogius compounds based on expert judgement.

Data source

Reference

Reference Type:

publication

Title:

HERA report on alcohol ethoxylates

Author:

A.I.S.E. / CEFIC

Year:

2009

Bibliographic source:

http://www.heraproject.com/RiskAssessment.cfm?SUBID=34

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Investigation of absorption, distribution, metabolism and excretion of alcohol ethoxylates

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethoxylated alcohols (C12 with 3 or 6 EO)

IUPAC Name:

Ethoxylated alcohols (C12 with 3 or 6 EO)

Test material form:

other: paste, liquid (depending on alcohol ethoxylate tested)

Details on test material:

Ethoxylated alcohols (C12 with 3 or 6 EO)

Radiolabelling:

other: partly

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

other: Oral / Dermal

Vehicle:

not specified

Details on exposure:

Various exposure routes and form of administration (for details see summary section)

Duration and frequency of treatment / exposure:

Various study periods (for details see summary section)

Doses / concentrations

Remarks:

Doses / Concentrations:
Various doses (for details see summary section)

No. of animals per sex per dose / concentration:

Various animal numbers (for details see summary section)

Control animals:

other: various (for detatils see summary section)

Details on study design:

Various test protocols

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, carcass, expired air, various tissues and organs
- Time and frequency of sampling: various

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Alcohol ethoxylates are readily absorbed in the gastrointestinal tract (>75% oral absorption following oral administration).

Main ADME results 2

Type:

distribution

Results:

no significant distribution, no bioaccumulation

Main ADME results 3

Type:

metabolism

Results:

two distinct polar metabolites detectable independent of ethoxylated alcohol investigated

Main ADME results 4

Type:

excretion

Results:

Rapid and almost complete excretion ( 90% within first 24 hours; 98-99% within 72 hours)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Alcohol ethoxylates of various C-chain length and ethoxylation degree are quickly and readiliy absorbed in the gastrointestinal tract following oral administration.

Details on distribution in tissues:

No indication of significant distribution in tissues and organs even at relatively high doses.

Details on excretion:

Rapid and almost complete excretion via urine, faeces and CO2. No dose-dependant differences in elimination observed.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

For each ethoxylated alcohol, two major polar metabolites were detected. Most probably resulting from the oxidization of the alcohol chain with the ethoxylate residue remaining intact.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Based on the very comparable toxicokinetic results with close structural analogous ethoxylated alcohols of various C-chain length and ethoxylation degrees, the registered ethoxylated alcohol is considered to be readily absorbed. Excretion is rapid and almost complete.

Executive summary:

Absorption, distribution, metabolism and excretion of different C14 -labelled ethoxylated alcohols (C12 with 3, 6 and 10 EO) was investigated in Wistar rats following oral and dermal exposure. Following administration the animals were placed in metabolism cages for 4 days and faeces, urine and expired air were monitored for C14 activity. At termination, various tissues, organs and the carcass were analysed for radioactivity. Relative amounts of test compounds found in urine, faeces, air and carcass did not differ significantly and recoveries were almost 100% for both exposure routes. The results suggests nearly complete absorption from the gastrointestinal tract for the shorter ethoxylate chain compounds whereas longer ethoxylate chain compounds may be partly excreted via bile or into the intestine by other routes. For each investigated ethoxylated alcohol, two distinct polar metabolites were detected in urine which are most probably resulting from the oxidization of the alcohol chain while the ethoxylate residue remains intact. In a separate study, the absorption, distribution and elimination kinetics of a C14 labelled C14 -18 fatty alcohol with 10 EO was investigated following single oral doses up to 1000 mg/kg body weight to Wistar rats. Urine, faeces and labelled CO2 were monitored daily over a period of 4 days. To investigate the distribution pattern, oesophagus, intestine, liver, kidney and blood were also monitored for C14 activity. Based on the results, a comparable kinetic behaviour to previous studies was observed. The ethoxylated alcohol was readily absorbed from the gastrointestinal tract with penetration rates of 80 - 90 %, elimination was rapid and almost complete and only very low levels of radioactivity were detected in the investigated organs. Based on all available reports, fatty alcohol ethoxylates of various chain length and ethoxylation degrees are absorbed quickly and extensively following oral exposure while dermal absorption is more slowly and incomplete. Elimination is rapid and almost complete whith urinary excretion being the major pathway with smaller amounts appearing in faeces (most probably due to biliary excretion) and CO2. From the toxicokinetic data, no indications of a bioaccumulative potential of ethoxylated alcohols exist.