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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
yes
Radiolabelling:
no
Species:
human
Sex:
female
Details on test animals and environmental conditions:
Skin region: abdomen
BMI: 22.7-35.5
Type of coverage:
occlusive
Vehicle:
other: HBSS-buffer
Duration of exposure:
24 h
Doses:
10%
No. of animals per group:
3 donors (n=2)
Control animals:
no
Details on study design:
According to Guideline.
Absorption in different matrices:
The mean amount of sodium laureth sulfate (SLS) removed from the skin surface (skin wash) ranged from 87.16% to 94.56% of the dose applied in the mean values of the 3 skin donors. This demonstrates that the SLS has mostly remained on the skin surface. The amounts in the receptor could not be quantified, since it was below the analytical lower limit of quantification (LLOQ). The mean recovery in the two first tape strips was 1.48% during all performed experiments. In the further 18 tape strips a mean recovery of 2.86% was documented. The recovery values for the cryocuts have accounted 0.56% in mean. The mean recovery values have varied from 90.90% to 100.21%, which complies to the acceptance criteria of 100 ± 15%.
The mean absorbed dose of SLS, sum of the amounts found in the viable epidermis, dermis and receptor medium was 0.56%.
Total recovery:
90.90% - 100.21%
Dose:
10%
Parameter:
percentage
Absorption:
< 1 %
Remarks on result:
other: 24 h
Remarks:
The mean absorbed dose of SLS, sum of the amounts found in the viable epidermis, dermis and receptor medium was 0.56%.
Conclusions:
The mean absorbed dose of sodium laureth sulfate (SLS), sum of the amounts found in the viable epidermis, dermis and receptor medium and the mean recovery of SLS found in the deeper skin layers sum up to 0.56%.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
other: rat and human
Details on test animals 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:
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:
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.