Toxicology of Industrial Compounds

Figure 19.7 Toxicological loci in H-P-T-L axis.
C.K.ATTERWILL AND S.P.AYLWARD 267
metabolism, hepatic elimination and thus circulating TSH levels (see also
Capen and Martin, 1989; McClain, 1989; Atterwill et al., 1993). The
xenobiotics include phenobarbital (McClain, 1989), β-naphthoflavone
(Johnson et al., 1993), the polychlorinated biphenyls (Bastomsky, 1974),
diproteverine (a calcium antagonist; Flack et al., 1989), SC37211 (a Searle
imidazole antimicrobial (Comer et al., 1985), L649923 (a leukotriene D 4
antagonist; Saunders et al., 1988), a novel oxyacetamide-FOE 5043
(Christenson et al., 1993), alachlor (Brewster et al., 1993), PCNB
(pentachloronitrobenzene; Story et al., 1993), and hexachlorobenzene
(Ogilvie and Ramsden, 1988).
Most of these compounds have thus far been assumed to act in vivo via
the induction of hepatic uridine diphosphate glucuronosyltransferase (UDP-
GT) in the rat, with species-specific formation of thyroid tumours in
carcinogenicity studies (see McClain, 1989). Indeed many of the
compounds, including phenobarbital do lead to increased hepatic UDP-GT
activity and appearance of glucuronidated T 4 in the bile, sometimes with
elevated bile flow rates (see McClain, 1989). However, others such as the