Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of 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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A study was performed to determine the P450 dependency of omega and omega-1-hydroxylation of various fatty acids, including lauric acid. The omega and omega-1-hydroxylations were determined by incubating microsomes (0.3 mg protein) in a mixture containing 100 uM fatty acid (0.5 uCi) in 0.12 M potassium phosphate with a pH of 7.4. HPLC was then used to determine the metabolites. Inhibition of the CYP2E1 enzyme by following a similar procedure, but adding 100 mM of DMSO and using 0.05 mM lauric acid. Anti-CYP2E1 and anti-CYP4A1 antibodies were also assayed.
GLP compliance:
no

Test material

Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich-Sigma

RADIOLABELLING INFORMATION (if applicable)
- Specific activity: 50 mCi/mmol
- Locations of the label:1-14C
Radiolabelling:
yes

Test animals

Species:
other: human, dog, rat, mouse, gerbil, hamster, monkey
Strain:
other: rat- SD, mouse - Swiss, hamster - mongolian, dog - beagle, monkey - cynomolgus

Administration / exposure

Statistics:
Correlation coefficients were calculated using an ANOVA table by the least-square regression analysis.

Results and discussion

Main ADME resultsopen allclose all
Type:
metabolism
Results:
Lauric acid was the most actively metabolized fatty acid regardless of species. All other fatty acids contained longer carbon chains.
Type:
metabolism
Results:
DMSO inhibited the omega-1-hydroxylation of lauric acid, but not the omega-hydroxylation of lauric acid, indicating lauric acid is metabolized by CYP2E1 by omega-1-hydroxylation.
Type:
metabolism
Results:
Anti-2E1 also significantly inhibited the omega-1-hydroxylation of lauric acid, but not the omega-hydroxylation, again indicating that lauric acid is metabolized by CYP2E1 via omega-1-hydroxylation.
Type:
metabolism
Results:
Anti-4A1 did not inhibit the omega-1-hydroxylation of lauric acid, but did significantly inhibit the omega hydroxylation of lauric acid. This indicates CYP4A1 is involved in omega-hydroxylation, but not omega-1-hydroxylation.
Type:
metabolism
Results:
omega-1-hydroxylation of lauric acid was significantly correlated with the levels of cytochrome P450 2E1 (r=0.94).
Type:
metabolism
Results:
omega-Hydroxylation of lauric acid was significantly correlated with the levels of cytochrome P450 4A1 (r=0.75).

Applicant's summary and conclusion

Executive summary:

A study was performed to determine the P450 dependency of omega and omega-1-hydroxylation of various fatty acids, including lauric acid. The omega and omega-1-hydroxylations were determined by incubating microsomes (0.3 mg protein) in a mixture containing 100 uM fatty acid (0.5 uCi) in 0.12 M potassium phosphate with a pH of 7.4. HPLC was then used to determine the metabolites. Inhibition of the CYP2E1 enzyme by following a similar procedure, but adding 100 mM of DMSO and using 0.05 mM lauric acid. Anti-CYP2E1 and anti-CYP4A1 antibodies were also assayed. Results showed that omega-1-hydroxylation of lauric acid was significantly correlated with the levels of cytochrome P450 2E1 (r=0.94), and omega-hydroxylation of lauric acid was significantly correlated with the levels of cytochrome P450 4A1 (r=0.75).