Page 181 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

148 SECTION | I General

VetBooks.ir TABLE 9.2 Proposed Administration Routes of Test desirable in order to reveal reproductive toxicological
data (OECD, 2001a; Barlow et al., 2002; Garg et al.,
Compounds in Laboratory Animals Based on the
2011; Estevan et al., 2011), although this approach
Medium of Exposure requires large numbers of animals and is time consuming.
Medium of Human and Domestic/ Administration
Farm Animal Exposure to Toxicant Route
Developmental Toxicity Testing
Food commodities Oral
Developmental toxicity testing is primarily used to deter-
Water Oral
mine hazard regarding the potential effects of prenatal
Inhalation exposure on the developing fetus. These studies focus on
Dermal functional and structural changes that can be observed
throughout the development from zygote to neonate. The
Air Inhalation
most important developmental phase is the organogenesis
Household/environmental surfaces Oral period that is always taken into account in developmental
Dermal toxicity testing. Based on these studies, chemical com-
pounds can be categorized as teratogenic and/or fetotoxic
by recording structural malformations, developmental
retardation and/or mortality, respectively. The vast major-
ity of teratogenic chemical agents have been identified
TABLE 9.3 Selective Endpoints Applied to Laboratory using rodent experimental models (EPA, 1998b, 2000;
Animals During Reproductive Toxicity Testing OECD, 2001b, 2016a,b). However, the failure of rodents
to detect teratogenic signal on some occasions and the
Female Male
similarities in placentation and pregnancy physiology
Reproductive tract Sperm structure/morphology between humans and rabbits led to the use of the rabbit as
morphology
a second model for assessing the effects of toxic com-
Reproductive tract receptors Sperm motility/viability/count pounds on development (EPA, 1998b; Foote and Carney,
Ovum properties Sperm DNA integrity 2000; OECD, 2001b). Furthermore, although nonhuman
primates have been suggested as models for teratological
Recovery of blastocysts Hormonal balance/receptor
interactions testing (Buse et al., 2003; Faqi, 2011), they have several
limitations such as a long gestation period, only single
Hormonal balance/receptor Fertility testing interactions
or twin offspring, high rates of abortion and ethical
Length and normality of constraints.
estrus cycle
The detection rates for veterinary pharmaceutical
Fertility testing agents demonstrated to be teratogenic/fetotoxic were
found to be 55% 79% using individual species (Hurtt
Uterine condition
et al., 2003). However, when the rat and rabbit data were
Implantation
both considered, there was a significant increase in detec-
Lactation tion rate to almost 100%, suggesting that in the absence
Maternal behavior of teratogenicity in rat, a second species developmental
test in lagomorpha is required to provide high standards
of public protection (Hurtt et al., 2003). The interested
reader can retrieve some more information on reproduc-
tive and developmental toxicity testing by referring to a
Some of the disadvantages of using rabbits are the higher
specialized textbook (Gupta, in press).
cost due to greater amounts of chemical compounds
administered and the increased cases of abortions because
of the relatively high incidence of gastrointestinal dys- Cutaneous Toxicity Testing
function. For example, rabbits are poor models for veteri-
nary residue testing and, more specifically, for antibiotics The aim of in vivo assays for cutaneous toxicity is not
because these compounds have been found to cause diar- only to assess potential acute local irritation but also to
rhea and consequently abortion (Barlow et al., 2002). evaluate acute, subchronic and chronic systemic toxic
Since exposure to chemicals can occur throughout life, effects. During cutaneous toxicity tests, animals are moni-
a multigeneration study that extends over at least two gen- tored for skin reactions/dermal effects, clinical, gross or
erations, using a single type of laboratory rodent, is microscopic pathological findings depending on the