Page 714 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

PCBs, PBBs, Dioxin, PCDDs Chapter | 51 679

VetBooks.ir of 17 days and 31 days were calculated for chick muscle does not explain entirely the 10- to 100-fold difference in
acute toxicity between the hamster and other rodent
and liver, respectively, and the concentration of PBBs in
species.
adipose tissue was essentially unchanged after 56 days
(Ringer and Polin, 1977; Polin and Ringer, 1978a, b).
TOXICITY
PCDDs and PCDFs
Exposure to PBBs, PCBs, PCDDs, and PCDFs has been
The absorption, distribution, metabolism, and elimination linked with a broad spectrum of effects, both in vivo and
of PCDDs and PCDFs have been extensively reviewed by in vitro, which vary depending on method/age of expo-
Van den Berg et al. (1994). Absorption from the gastroin- sure, sex of the individual, and dose/duration of exposure
testinal tract of mammals is effective, and can exceed (Steinberg et al., 2008). Fetal and early developmental
75% of the dose for the lower chlorinated congeners. exposures to these chemicals are particularly devastating,
With increasing molecular size, absorption from the intes- and can have different outcomes from adult exposure
tines is greatly reduced, which is most apparent for the (Crews et al., 2000).
hepta- and octa-chlorinated congeners. The liver and adi-
pose tissue are the major storage sites of PCDDs and Male Reproductive Effects
PCDFs for most mammalian and avian species. Whole-
body half-lives of 2,3,7,8-substituted congeners in rodents TCDD and related compounds decrease testis and acces-
range from a few to more than 100 days. The extent of sory sex organ weight, cause abnormal testicular morphol-
absorption of TCDD or related compounds is variable, ogy, decrease spermatogenesis, and reduce fertility when
depending on the vehicle and the substitution pattern of given to adult animals in doses sufficient to reduce food
the congener. There appear to be no differences between intake and/or body weight. Some of these effects have
species in terms of absorption of these compounds been reported in chickens, rhesus monkeys, rats, guinea
through the gastrointestinal tract. Studies with rats, mice, pigs, and mice treated with toxic doses of these chemi-
hamsters, guinea pigs, cows, and chickens, in general, cals. Effects on reproductive hormones in human males
indicate that tetra- and penta-chlorinated congeners are have also been characterized (Makey et al., 2016a).
well absorbed from the gastrointestinal tract (50% 90%), TCDD effects on spermatogenesis are characterized by
but octa is absorbed only to a limited extent (2% 15%) loss of germ cells, the appearance of degenerating sper-
(Van den Berg et al., 1994). matocytes and mature spermatozoa within the lumens of
As in mammals, the liver and adipose tissue of avian seminiferous tubules, and a reduction in the number of
species are the major sites for storage and accumulation tubules. Effects of TCDD on the male reproductive sys-
of 2,3,7,8-substitiuted PCDDs and PCDFs. Hepatic depo- tem are thought to be due, in part, to an androgen defi-
sition of 2,3,7,8-substituted PCDDs and PCDFs appeared ciency, caused by decreased plasma testosterone and
to increase with increasing chlorination, resulting in a dihydrotestosterone levels concomitant with unchanged
limited transfer of the more highly chlorinated congeners plasma clearance of androgens and luteinizing hormone
to the egg (Van den Berg et al., 1994). In mammals, the (LH) (Peterson et al., 1993; Safe, 1994). Pflieger-Bruss
liver and adipose tissue are the major compartments for et al. (2004) provide a review of the effects of various
the deposition of PCDDs and PCDFs. The elimination of endocrine-disrupting chemicals, including PCBs/PCDDs/
polar metabolites of 2,3,7,8-substituted PCDDs and PCDFs, on the male reproductive system.
PCDFs occurs predominantly via the bile and feces, with Foster et al. (2010) state that decreased sperm counts
urinary excretion playing a minor role. As chlorine con- are considered to be the most sensitive outcome of the
tent increases, the rate of elimination of PCDDs and reproductive/developmental effects of TCDD. A single
PCDFs decreases (Pohjanvirta and Tuomisto, 1994; Van exposure of pregnant rats to 0.064 μg TCDD/kg body
den Berg et al., 1994). weight on gestational day (GD) 15 resulted in a signifi-
Interspecies differences in toxicity can only be partly cant decrease (36%) in epididymal sperm counts (Mably
explained by differences in toxicokinetics. The guinea pig et al., 1992). The World Health Organization (WHO)
is most sensitive to the acute effects of TCDD and has the used this endpoint to establish a tolerable daily intake for
slowest metabolism and elimination of TCDD, suggesting TCDD of approximately 2 pg/kg body weight/day (Foster
that toxicokinetics, in part, explains the unique sensitivity et al., 2010). Further reports show that developmental
of the guinea pig to the acute toxicity of TCDD and exposure to PCBs and the plasticizer di(2-ethylhexyl)
2,3,7,8-TCDF (Van den Berg et al., 1994). The hamster is phthalate (DEHP) alters adult F1 males’ reproductive
the species most resistant to the acute toxicity of TCDD. health. Both dioxin-like and nondioxin-like PCB can alter
Although the elimination rate of TCDD is two- to three- the timing of puberty in males (Burns et al., 2016). High
fold greater in the hamster than the rat and mouse, this exposure of PCBs in humans during their lifetime have