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Diss Factsheets

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Supporting study, no GLP, No guideline required.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2013
Reference Type:
publication
Title:
The Use of Everted Rat Small Intestinal Sacs In Vitro to Estimate Relative Absorption Potential of a Series of Alpha Olefins. Annual Meeting Abstract Supplement, Society of Toxicology, 2015 Abstract no. 1593
Author:
Penman M, Powrie RH and Elcombe CR
Year:
2014
Bibliographic source:
Annual Meeting Abstract Supplement, Society of Toxicology, 2015 Abstract no. 1593

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
In vitro gut absorption study
GLP compliance:
no
Type of method:
in vitro
Endpoint addressed:
other: in vitro gut absorption

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Male Han Wistar rats (approx. 8-12 weeks old) were obtained from Harlan, Bicester, UK.

Administration / exposure

Route of administration:
other: gut absorption model
Vehicle:
not specified

Results and discussion

Details on results:
The C6, C8-C10 (C9 Rich) and C10 molecules were readily absorbed into the intestinal sacs. Marked inter-compound differences were observed, with the amount of absorption generally decreasing with increasing Carbon number. Olefins with 14 carbons and over were either not absorbed or very poorly absorbed (Figure 1).
The results can be explained analyzing the differences between olefins and dietary-derived fatty acids, which derived from the liase-mediated hydrolysis of dietary triglycerides in the small intestine. In fact, the fatty acids contain an ionisable caboxylic acid function. Due to the small intestine pH, a great amount of fatty acids exist in the form of carboxylate anions in the small intestine. Fatty acid In fact they are absorbed via the intestinal villi and reassembled into triglycerides and/or via a specific fatty acid transporter protein in the membrane. The carboxylic acid functional group is essential in this step. In addition, a considerable fraction of the fatty acids also enter the enterocyte via a specific fatty acid transporter protein in the membrane.The Vitamin K (lipophilic compound) was also tested. Results showed the poor absorption as well as the olefins >12 C.

Applicant's summary and conclusion

Conclusions:
Olefins containing C6, C8 -C10 (C9 Rich) and C10 molecules were readily absorbed into the intestinal sacs. Marked inter-compound differences in absorption were observed, with the amount of absorption decreasing profoundly with increasing Carbon number.
 
Executive summary:

An in vitro gut absorption study was performed to determine and rank the intestinal absorption potential of a series of alpha-olefins (Table1). Everted sacs were incubated in “Fed-state Simulated Small Intestinal Fluid” saturated with individual olefins. The sac contents were then collected, extracted and analysed for olefin content using gas chromatography with flame ionisation detection. The result of the study showed that the olefins containing C6, C8 -C10 (C9 Rich) and C10 molecules were readily absorbed into the intestinal sacs. Marked inter-compound differences in absorption were observed, with the amount of absorption decreasing profoundly with increasing Carbon number.