Page 731 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

696 Section |IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir (Covaci et al., 2006; Law et al., 2006) and that individual manners (Zhao et al., 2015,2017). Elimination rates and
half-lives of PFCs vary with carbon chain length and ani-
diastereomers have different physical and chemical proper-
mal species and gender tested. Hanhijarvi et al. (1988)
ties. There is a growing need to understand the individual
diastereomers that make up the commercial mixture. reported that male hamsters excrete PFOA more rapidly
There are significant differences in the pharmacoki- than do females. In dogs, the half-life of PFOA is 20 30
netic behavior of individual PBDE congeners and mix- days in males and 8 13 days in females. However, gender
tures. These differences in absorption, distribution, differences are not discernible in mice or rabbits (Hundley
metabolism, and excretion depend on the test animal spe- et al., 2006; Lau et al., 2006). The cause for gender and
cies and the degree of bromination. As the number of bro- species differences in elimination of PFCs is not eluci-
mine atoms increases from 4 to 10 bromines (tetraBDE to dated. Buist and Klaassen (2004) attributed these differ-
decaBDE), there are decreases in oral absorption, which ences to the functions of organic anion transporters in the
leads to shortened half-lives and increased elimination in kidney because several transporter proteins are expressed
both urine and feces. DecaBDE is poorly absorbed, with differentially in male and female adult rats. Due to gender
greater than 90% of the dose excreted in feces within 48 h and species differences in elimination of PFCs, careful
(Morck et al., 2003). Workers occupationally exposed to consideration must be given to compare toxicological
decaBDEs have shown decaBDE half-lives of approxi- effects. Further studies with emphasis on body burden
mately 15 days (Thuresson et al., 2006), which is consid- rather than administered dose are warranted.
erably shorter than those of other lower brominated
congeners. DecaBDE has been found in the blood and
breast milk of humans in the general population, but at MECHANISM OF ACTION AND TOXICITY
lower levels than other PBDE congeners (Hendriks and Brominated Flame Retardants
Westerink, 2015; Lorber, 2008).
Lower brominated PBDEs, in contrast to decaBDE, TBBPA is of high ecotoxicologic concern due to its acute
are more readily absorbed and persist in the body for and chronic toxicity in several biota (U.S. EPA, 2008;
many years because they are mainly stored in body fat. Lyche et al., 2015). TBBPA has been shown to be rapidly
PBDE-47 and PBDE-99 are well absorbed and highly dis- metabolized by mammalian livers and eliminated in bile,
tributed to lipophilic tissues, such as adipose, skin, and urine, and feces (Schauer et al., 2006). TBBPA has been
liver tissue (Hakk et al., 2002; Staskal et al., 2005). In detected in various environmental media and biota,
rats, tetra- and pentaBDEs are metabolized and eliminated including air, soil, water, sediment, and bird muscle from
slowly (Hakk et al., 2002), whereas in mice, PBDE-47 is electronic waste processing regions of China (Shi et al.,
well absorbed and distributed, but its elimination is also 2009; Liu et al., 2016), and also in bottlenose dolphins
rapid (Staskal et al., 2005). Uptake efficiencies of PBDE- and bull sharks from the Florida coast (Johnson-Restripo
47, PBDE-99, and PBDE-153 by pike fed trout injected et al., 2008). Currently, no restrictions are placed on the
with the congeners were 90%, 62%, and 40%, respec- production and use of TBBPA. TBBPA is a cytotoxicant,
tively (Burreau et al., 1997). immunotoxicant, and thyroid hormone (TH) agonist, and
it has the potential to disrupt estrogen signaling
Perfluorinated Compounds (Birnbaum and Staskal, 2004). TBBPA is also toxic in rat
brain cells in vitro, where it causes oxidative stress, cal-
Very limited information is available on the pharmacoki- cium influx, and inhibits dopamine uptake (Reistad et al.,
netics and toxicokinetics of perfluorochemicals in farm or 2007). In vivo studies indicate that neonatal TBBPA
domestic animals. Laboratory animal studies have shown exposure causes hearing deficits in rat offspring, similar
that PFOS and PFOA are well absorbed orally, not metab- to those observed following developmental exposure to
olized, and poorly eliminated (Ophaug and Singer, 1980; PCBs (Lilienthal et al., 2008). Nakajima et al. (2009)
DuPont Company, 1982; Johnson et al., 1984; Vanden reported the presence of TBBPA in brain along with
Heuvel et al., 1991; Guruge et al., 2006; Chang et al., behavioral alterations following acute treatment of
2012; Butenhoff and Rodricks, 2015). Upon ingestion, TBBPA. Disruption of TH homeostasis is proposed to be
these compounds are distributed primarily to the liver, kid- the primary toxic effect of TBBPA and other BFRs.
ney, and serum, with liver concentrations being the highest TBBPA has a closer structural relation to thyroxine (T 4 )
(Seacat et al., 2002, 2003; Hundley et al., 2006). PFOS than to PCBs and binds to transthyretin (TTR) with
and PFOA tend to bind to β-lipoproteins (Jones et al., greater affinity than it does to T 4 (Meerts et al., 2000). A
2003), albumin, and liver fatty acid binding protein study utilizing F344 rats and B6C3F1/N mice conducted
(Luebker et al., 2002). Perfluoroalkyl sulfonates (PFSAs) by the U.S. National Toxicology Program (NTP), showed
such as PFHxS and PFOS are transported into hepatocytes a significant fall in serum total T 4 levels at the 500 and
in both sodium-dependent and sodium-independent 1000 mg/kg doses in both males and females (NTP,