Fatty acids, C16-18 and C18-unsatd., dimerized

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

The percutaneous absorption of some anionic surfactants

Author:

Howes, D.

Year:

1975

Bibliographic source:

J. Soc. Cosmet. Chem. 26:47-63

Materials and methods

Objective of study:

excretion

Principles of method if other than guideline:

Turnover of [14C] surfactants in the rat

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid (C10:0), Dodecanoic acid (C12:0), Tetradecanoic acid (C14:0), Hexadecanoic acid (C16:0), Octadecanoic acid (C18:0)

IUPAC Name:

Decanoic acid (C10:0), Dodecanoic acid (C12:0), Tetradecanoic acid (C14:0), Hexadecanoic acid (C16:0), Octadecanoic acid (C18:0)

Details on test material:

- Name of test material (as cited in study report): Decanoic acid (C10:0), Dodecanoic acid (C12:0), Tetradecanoic acid (C14:0), Hexadecanoic acid (C16:0), Octadecanoic acid (C18:0)
- Analytical purity: Pure biochemical grade
- Specific activity (if radiolabelling): 14 mCi/mM
- Locations of the label (if radiolabelling): 1-Alkyl position with 14C (1-14C)

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100-120 g
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

other: intraperitoneal (3 animals) and subcuntaneous (3 animals)

Vehicle:

other: The test materials were applied as soap solutions (sodium salts).

Duration and frequency of treatment / exposure:

6 h

Doses / concentrations

Remarks:

Doses / Concentrations:
C10:0: ca. 1.09 mg/kg bw
C12:0: ca 1.18 mg/kg bw
C14:0: ca. 1.36 mg/kg bw
C16:0: ca. 1.55 mg/kg bw
C18:0: ca. 1.64 mg/kg bw

No. of animals per sex per dose / concentration:

6: 3 animals injected intraperitoneally, 3 animals injected subcutaneously

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (excretion)
- Tissues and body fluids sampled: urine, faeces, expired air
- Time and frequency of sampling: single sampling at 6 h post-application

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

The rate and route of excretion of 14C from intraperitoneally administered [14C] surfactant solutions were the same as that from subcutaneously administered solutions. The recoveries are given in Table 1 (see remarks on results).
These results showed that at 6 h after administration, the C10:0 and C12:0 soaps were readily metabolized and the main route of excretion was as 14CO2, The C14:0 soap was readily incorporated into the body and the 14C excretion was slow. The C16:0 and C18:0 soaps showed some metabolism with subsequent 14CO2 excretion but most of the 14C was recovered in the carcass at 6 h. From the results the route of excretion of 14C surfactant giving the most sensitive indication of percutaneously absorbed surfactant was indicated.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Table 1. Recoveries of 14C from rats after injection with [14C] surfactants.

 

	Dose		% Applied dose
[14C] Surfactant	µCi	(mg)	CO2	Urine	Faeces	Carcass
C10:0	7.25	0.12	57 ± 5	< 0.1	< 0.1	37 ± 6
C12:0	10.49	0.13	65 ± 7	< 0.1	< 0.1	30 ± 7
C14:0	8.13	0.15	5 ± 3	2.1 ± 1.2	< 0.1	85 ± 9
C16:0	7.74	0.17	21 ± 4	< 0.1	< 0.1	71 ± 8
C18:0	8.49	0.18	38 ± 9	< 0.1	< 0.1	56 ± 16

 

Each result is the mean from six animals ± SD – three animals injected intraperitoneally and three animals subcutaneously. The collection time was 6 h after injection.

Applicant's summary and conclusion

Conclusions:

The turnover of the [14C] surfactants in the rat showed that there was no significant difference in the rate or route of excretion of 14C given by intraperitoneal or subcutaneous administration. The main route of excretion was as 14CO2 in the expired air at 6 h after administration. The remaining material was incorporated in the body. Longer fatty acid chains are more readily incorporated than shorter chains. At ca. 1.55 and 1.64 mg/kg bw, 71% of the C16:0 and 56% of the C18:0 was incorporated and 21% and 38% was excreted as 14CO2, respectively.