Page 505 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

472 SECTION | V Metals and Micronutrients

VetBooks.ir Due to nonspecific protein incorporation of selenomethio- (Hoffman, 2002; Kaur et al., 2003; Balogh et al., 2004).
A third theory is the incorporation of selenium com-
nine, urinary and fecal recovery after dosing was less than
pounds in place of sulfur, such as in proteins, in which it
30% of that for equal selenium doses from selenite or sel-
enate (Thomson, 1998). disrupts normal cellular functions (Raisbeck, 2000). This
The literature suggests that the predominant selenium is an especially likely mechanism for the hair and hoof
elimination in ruminants is fecal when ingested, but uri- lesions of chronic selenium poisoning, with the loss of
nary with parenteral administration or in nonruminating disulfide bridges that provide structural integrity to these
young animals. This is actually an error in terminology, tissues. This would also apply to inhibition of DNA
as the fecal loss of selenium is primarily in the form of methylation by S-adenosylmethionine or indirect inhibi-
elemental selenium and precipitated selenides from rumi- tion by increased S-adenosyl homocysteine content
nal reduction (Langlands et al., 1986). Thus, this selenium (Hoffman, 1977). And, it is possible that each of these
is nonabsorbed material and is not truly being eliminated proposed mechanisms is valid with respect to specific
from the central compartment. However, a small amount chemical forms of selenium. It has been observed that
of metabolized selenium excesses is excreted in the bile tissues requiring selenium to prevent deficiency-
(Cousins and Cairney, 1961). The selenium metabolites associated disease (immune system, reproductive organs
eliminated in the urine follow a similar pattern to that and muscular tissues) also tend to accumulate more sele-
seen with monogastrics. Urinary elimination is predomi- nium with excess exposure and are the primary tissues
nant with parenteral administrations and in nonruminating of toxic effects.
young animals (NRC, 1983).
Renal selenium elimination is dependent of glomerular TOXICITY
filtration and degree of reabsorption. Increasing renal
fluid absorption did not increase the selenium content in Selenium poisoning cases generally fall into three types
urine, indicating a tubular reabsorptive process (Oster and of exposure history. The first is from ingestion of sele-
Prellwitz, 1990). Thus, dehydration or renal insufficiency nium in plants that have accumulated it from naturally
would decrease rates of elimination. Excretion and renal seleniferous soils. The second is from accidental over-
clearance rates correlate with creatinine, indicating glo- doses by injection or errors in feed mixing. And the third
merular filtration is the mechanism of elimination. is from environmental contamination, which often results
Some selenium is eliminated via respired air, but the in exposure from plant accumulation and/or contaminated
relative importance of this route is dose dependent. At nor- waters. With each of these types of poisonings, one may
mal intake, only about 10% or less is eliminated from the see acute, subacute or chronic selenium poisoning,
respiratory tract (Burk et al., 1972), but as dose increases depending upon the daily exposure rate. However, one
the percent eliminated in respired air increases (Jacobsson, must understand that an animal’s age plays a role in sus-
1966; McConnell and Roth, 1966). Dimethylselenide and ceptibility to selenium poisoning, as young animals are
dimethyldiselenide are the predominant forms eliminated less tolerant than adults (Raisbeck, 2000).
in respired air at toxic doses. Dimethylselenide predomi- Doses for acute selenium toxicosis vary significantly
nates when mice were dosed with selenite or selenocys- across species, but also by route of exposure, with
teine, while dimethyldiselenide is most abundant when rats injectable routes of exposure being more toxic than oral.
were dosed with selenomethionine. Respiratory elimination Acute oral selenium poisoning occurs with sudden expo-
is primary when renal elimination thresholds are maxi- sure ranging from 2.2 mg/kg (Rosenfeld and Beath, 1964)
mized, which results in most respiratory elimination occur- to greater than 20 mg/kg body weight (Miller and
ring in a short-time period soon after exposure to toxic Williams, 1940; Mahan and Moxon, 1984) across species.
doses (McConnell and Roth, 1966; Tiwary et al., 2005). The relative oral acute toxicity of selenium-containing
compounds is dependent on their solubility, with poorly
soluble selenides and elemental selenium being much less
MECHANISM OF ACTION
toxic than soluble selenates, selenites and organic sele-
Although much research has been conducted with regard nium (NRC, 2005). Minimum lethal dose for rabbits, rats,
to selenium poisoning, the exact mechanism of the toxic dogs and cats is 1.5 3 mg/kg body weight (NRC, 1983).
effects in the body are still not clear. With acute poison- The LD 50 for oral selenite has been estimated to be
ing, one theory is the depletion of intermediate substrates, 1.9 8.3 mg/kg body weight in ruminants (Grace, 1994),
such as glutathione and S-adenosylmethionine, which dis- but other references suggest it to be 9 20 mg/kg body
turbs their respective enzyme activities (Vernie et al., weight (Puls, 1994). In poultry, the acute oral LD 50
1978). Another potentially interactive theory is the of selenium is 33 mg/kg body weight. Injectable selenium
production of free radicals by the reaction of selenium is more acutely toxic than oral, with intramuscular
with thiols, causing subsequent oxidative tissue damage LD 50 of 0.5 mg/kg in lambs (Caravaggi et al., 1970).