Page 463 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

430 SECTION | V Metals and Micronutrients

VetBooks.ir exposure and accumulation in the bone. Greater than 95% exact mechanism of action is not known with certainty,
fluoride concentrations in blood and soft tissues rapidly
of the body burden of fluoride will be contained in the
increase, which leads to hypocalcemia. Sudden death
bones with bone levels dependent upon the amount of
fluoride ingested, duration of exposure, bioavailability, from acute fluoride exposure is thought to involve the
species, age, and diet of the animal involved. If dietary development of hyperkalemia or diminished Na/K-
fluoride exposure decreases, bone fluoride levels will ATPase activity and the inhibition of glycolysis (NRC,
decrease slowly over a long period of time. In cattle there 2005). Fluoride can induce oxidative stress and modulate
appears to be a partial placental barrier to the movement intracellular redox homeostasis, lipid peroxidation and
of fluoride to the fetus as even high levels of fluoride in protein carbonyl content (Ranjan et al., 2009; Dubey
the diet of the dam did not adversely affect the health of et al., 2013). Fluoride is thought to inhibit the activity of
the calves, even though higher fetal blood and bone fluo- antioxidant enzymes, such as superoxide dismutase, gluta-
ride concentrations resulted (NRC, 2005). Fluoride is thione peroxidase and catalase. Depletion of glutathione
excreted in the milk but this does not appear to be a sig- results in excessive production of reactive oxygen species
nificant source for the neonate. at the mitochondrial level, leading to the damage of cellu-
The major adverse effects of chronic excess fluoride lar components. In an experimental study, Agalakova and
ingestion concern the teeth and bones of affected animals. Gusev (2013) demonstrated that excessive chronic fluo-
Fluoride substitutes for hydroxyl groups in the hydroxyapa- ride consumption leads to accelerated death of erythro-
tite of the bone matrix, which alters the mineralization and cytes and anemia in rats. Fluoride can also alter gene
crystal structure of the bone. Bone changes induced by expression and cause apoptosis (Barbier et al., 2010).
excess fluoride ingestion, termed skeletal fluorosis or Genes modulated by fluoride include those related to the
osteofluorosis, include the interference of the normal stress response, metabolic enzymes, the cell cycle,
sequences of osteogenesis and bone remodeling with the cell cell communication and signal transduction.
resulting production of abnormal bone or the resorption of
normal bone. The fluoride content of bone can increase TOXICITY
over a period of time without other noticeable changes in
the bone structure or function. Once lesions start to There are a number of factors that influence the amount of
develop, they are usually bilateral and symmetric. The fluoride required to produce specific lesions and clinical
most consistent gross changes are abnormal bone formation signs including the amount of fluoride ingested, duration of
on the periosteal surface with thickening of the cortex. In exposure, bioavailability, species, age and diet of the animal
cattle, earliest clinical changes usually occur on the ribs involved. The point where fluoride ingestion becomes detri-
and mandible as well as the medial surfaces of the metatar- mental to the animal also varies from animal to animal.
sal and metacarpal bones. Histologically, bones will have Clinical signs develop slowly and can be confused with
abnormal remodeling and mineralization with irregular col- other chronic problems. Animals often show nonspecific
lagenous fibers and excess osteoid tissues. While an excess intermittent stiffness and lameness, which appear to be
of ingested fluorides can adversely affect the bones at any associated with periosteal overgrowth leading to spurring
time in the animal’s life, the bones in younger animals are and bridging near joints as well as ossification of ligaments,
more responsive to the excess fluoride. tendon sheaths and tendons. The clinical presentation may
Dental fluorosis develops when the period of excess easily be confused with other conditions, such as degenera-
fluoride intake occurs during the period of tooth develop- tive arthritis, but the lesions associated with fluorosis are
ment; in cattle this will generally be before 30 36 not primarily associated with articular surfaces. In severe
months of age. Teeth are affected during development cases, affected cattle may become progressively lamer and
with damage to ameloblasts and odontoblasts and the eventually may refuse to stand or may stand with rear legs
resulting abnormal matrix unable to mineralize normally upright and be on their knees to graze (Shupe and Olson,
(Shearer et al., 1978). Both enamel and dentine are 1983). Lameness in cattle leads to abnormal hoof wear with
adversely affected. Affected teeth may erupt with mot- elongated toes, especially in the rear legs. In long-term
tling (alternating white opaque horizontal areas or stria- studies with cattle on varying levels of fluoride intake, skel-
tions in the enamel), hypoplasia, dysplasia (abnormal soft etal neoplasms were not seen even in cattle with severe
dull white chalky enamel or horizontal zones of constric- osteofluoritic lesions (Shupe et al., 1992).
tion), erosion or pitting of enamel and affected teeth are A great deal of effort has gone into the classification
prone to excessive abrasion and discoloration. of dental lesions in cattle produced by excess fluoride
Acute fluoride toxicosis occurs when soluble forms of ingestion. The incisor teeth are evaluated for enamel
fluoride (e.g., sodium fluoride) are ingested in large defects and abrasion pattern. The usual classification sys-
doses. Absorption is rapid and clinical signs can appear tem ranges from a value of 0 for normal teeth to a value
within 30 60 min following ingestion. Although the of 5 for severe fluoride effects (Shearer et al., 1978;