To reduce the number
of animals and studies needed to fulfill the
information requirements as required by Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH) (EC no. 1907/2006),
a read-across approach was used to support approximately 30 higher
olefins. This study aimed to assess the absorption potential of higher
olefins through the gut wall as the experimentally determined bioavailability
which would strengthen the read-across hypothesis and justification,
reducing the need for toxicity studies on all of the higher olefins.
The absorption potential of a series of higher olefins (carbon range
from 6 to 28, with five configurations of the double bond) was determined
in the in vitro everted rat small intestinal sac model and subsequently
ranked. In addition, in silico approaches were applied to predict
the reactivity, lipophilicity, and permeability of higher olefins.
In the in vitro model, everted sacs were incubated in “fed-state
simulated small intestinal fluid” saturated with individual
higher olefins. The sac contents were then collected, extracted, and
analyzed for olefin content using gas chromatography with a flame
ionization detector. The C6 to C10 molecules were readily absorbed
into the intestinal sacs. Marked inter-compound differences were observed,
with the amount of absorption generally decreasing with the increase
in carbon number. Higher olefins with ≥C14 carbons were either
not absorbed or very poorly absorbed. In the reactivity simulation
study, the reactivity is well described by the position of the double
bond rather than the number of carbon atoms. In the lipophilicity
and permeability analysis, both parameter descriptors depend mainly
on the number of carbon atoms and less on the position of the double
bond. In conclusion, these new approach methodologies provide supporting
information on any trends or breakpoints in intestinal uptake and
a hazard matrix based on carbon number and position of the double
bond. This matrix will further assist in the selection of substances
for inclusion in the mammalian toxicity testing programme.
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