Registration Dossier

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Information was taken from several review documents published by national and international agencies on human health aspects of fatty acids in human nutrition, cosmetics and household cleaning products. This information represents the highest level of reliability and acceptance.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid and stearic acid
Author:
Cosmetic Ingredient Review
Year:
1987
Bibliographic source:
Journal of the American College of Toxicology, Volume 6, Numer 3
Reference Type:
publication
Title:
Human & Environmental Risk Assessment on ingredients of European household cleaning products, Fatty Acid Salts, Human Health Risk Assessment
Author:
HERA
Year:
2002
Bibliographic source:
http://www.heraproject.com/files/5-HH-04-HERA%20Fatty%20acid%20salts%20HH%20web%20wd.pdf
Reference Type:
publication
Title:
Toxicological evaluation of some food colours, emulsifiers, stabilizers, anti-cracking agents and certain others substances
Author:
World Health Organization (WHO)
Year:
1974
Bibliographic source:
WHO Food Additive Series No. 5
Reference Type:
publication
Title:
WHO FOOD ADDITIVES SERIES: 42, linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters
Author:
World Health Organization (WHO)
Year:
1999
Bibliographic source:
http://www.inchem.org/documents/jecfa/jecmono/v042je16.htm

Materials and methods

Objective of study:
absorption
excretion
Principles of method if other than guideline:
Review documents on human health aspects of ingredients in human nutrition, cosmetic products and household cleaning products. Information contained therein were collected and reviewed by national and international expert panels.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: via diet, cosmetics, household cleaning products

Test animals

Species:
human
Sex:
male/female

Administration / exposure

Route of administration:
other: oral, dermal
Details on exposure:
dietary intake, dermal application as cosmetics or dermal contact as household cleaning product
Duration and frequency of treatment / exposure:
daily

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
> 90% (av. 96-98% in healthy adult) via passive or facilitated diffusion
Type:
distribution
Results:
absorbed as micelle aggregates, esterified with glycerol in chylomicrons and very low density lipoproteins, and transported via the lymphatic system
Type:
excretion
Results:
via faeces <2%

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Fatty acids are an endogenous part of every living cell and are an essential dietary requirement. Proposed mechanisms for fatty acid uptake by different tissues range from passive diffusion to facilitated diffusion or a combination of both (Abumrad et al. 1984; Harris et al., 1980).
Details on distribution in tissues:
Fatty acids taken up by the tissues can either be stored in the form of triglycerides (98% of which occurs in adipose tissue depots) or they can be oxidised for energy via the β-oxidation and tricarboxylic acid cycle pathways of catabolism (normal fatty acid metabolism).

Metabolite characterisation studies

Details on metabolites:
Fatty acids, C16-C18 can be divided in three steps (1) activation and transport into the mitochondria (2) beta-oxidation and (3) electron transport chain. The fatty acid is completely oxidised in a process in which two carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. The resulting Acetyl-CoA can enter the citric acid cycle. After the beta-oxidation no further metabolites are present.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: bioaccumulation potential is not relevant since fatty acids C16-C18 are part of the typical European diet
Fatty acids C16-C18 is almost completely absorbed as micelle aggregates in the GI tract of humans and occurs via passive or facilitated diffusion. The chylomicrons and low-density lipid proteins are transported via the lymphatic system. The resulting linear fatty acids participate in normal fatty acid metabolism. During beta-oxidation in the fatty acid is completely oxidised resulting in Acetyl-CoA, no metabolites or residues are formed.