Chemistry Reference
In-Depth Information
congeners was studied in mice that had been fed diets containing a single isomer for
20 days. The estimated half-lives were as follows:
2,2′,3,3′-TCB
0.9 days
2,2′,4,4′-TCB
9.2 days
2,2′,5,5′-TCB
3.4 days
3,3′,4,4′-TCB
0.9 days
3,3′,5,5′-TCB
2.1 days
In another study (Gage and Holm 1976), the influence of molecular structure was
studied on the rate of excretion by mice for 14 different congeners. The results were
as follows:
Most rapidly eliminated
4,4′-DCB, 3,3′,4′,6′-TCB, 2,2′,3,4′,6′-PCB and 2,2′3,4,4′,5′-HCB
Most slowly eliminated
2,2′,4,4′,5,5′-HCB and 2,2′, 3,4,4′,5′-HCB
In the latter example, the most slowly eliminated compounds were nonplanar, and
lacked vicinal carbons in either the ortho-meta or the meta-para positions that were
without any chlorine substitution (i.e., there were no vicinal ortho-meta or meta-para
positions that were substituted solely with hydrogen). The more rapidly eliminated
compounds all possessed vicinal ortho-meta positions that were without chlorine sub-
stitution. In the former example, the most persistent compound was nonplanar, and
lacked carbons unsubstituted by chlorine in the meta-para positions. Interestingly,
both of the coplanar compounds were eliminated rapidly, even though one of them
(3,3′,5,5′-TCB) lacked unsubstituted vicinal carbons in either position. This suggests
that P4501A1/1A2 was able to hydroxylate the molecule reasonably rapidly without
any vicinal unsubstituted carbons, presumably without the formation of an epoxide
intermediate.
In a study with captive male American kestrels (Drouillard et al. 2001), birds
were dosed with Aroclor-contaminated diet and the toxicokinetics of 42 PCB conge-
ners contained therein was studied. Those congeners that were most rapidly cleared
contained vicinal meta-para hydrogen substituents on at least one phenyl ring. This
provides further evidence for the importance of “open” (i.e., not substituted by chlo-
rine) meta-para positions for metabolic attack, an issue that will be returned to in the
next section (Section 6.2.3).
Working with rats, Lutz et al. (1977) compared the rates of loss from blood of
4,-CB (rapidly metabolized) with that of 2,2′,4,4′,5′-HCB (slowly metabolized). Both
showed biphasic elimination, with the former disappearing much more rapidly than
the latter. Estimations were made of the rates of hepatic metabolism in vitro, which
were then incorporated into toxicokinetic models to predict rates of loss. The pre-
dictions for HCB were very close to actual rates of loss for the entire period of
Search WWH ::
Custom Search