Page 117 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

84 SECTION | I General

VetBooks.ir TABLE 5.5 LD 50 (mg/kg) for Various Nerve Agents of tepid 0.9% saline or water for at least 15 min. Reactive
skin decontamination lotion (RSDL) appears to be the
best available dermal decontamination agent (Hanssen
Tabun
VX
Route
Species
Soman
Sarin
et al., 2006). If RSDL is not accessible, wash all exposed
Mouse IP 0.050 animals three times with soap and water. The use of a
Dermal 1.08 7.8 1 dilute bleach solution (1:10 with water), ethanol or tinc-
ture of green soap may be more efficacious (Cancio,
IM 0.089
1993).
Rat SQ 0.162 0.012
Emesis is not recommended in oral ingestion due to
Oral 0.55 3.7 the rapid development of signs. Activated charcoal might
provide benefits even after a topical exposure. Control
Dermal 18
seizures with diazepam, methocarbamol or barbiturates as
IM 0.062
needed before proceeding with other treatments.
Human Dermal 28 5 14 0.14 Atropine sulfate is a reversal agent. It is used for the
treatment of muscarinic effects of nerve agent poisoning,
Source: Data from RTECS, 2006. Registry of Toxic Effects of Chemical
Substances. National Institute for Occupational Safety and Health. but will not reverse nicotinic effects (muscular fascicula-
Cincinnati, OH (CD Rom Version). Edition expires 2006; provided by
Thomson MICROMEDEX, Greenwood Village, CO; Sidell, F.R., Takafuji, tions and weakness). Atropine does not affect the
E.T., Franz, D.R., 1997. Textbook of Military Medicine: Medical Aspects AChE insecticide bond, but blocks the effects of accu-
of Chemical and Biological Warfare. TMM Publications, Washington, DC.
mulated acetylcholine at the synapse. Atropinization
should be continued until the nerve agent is metabolized
(Midtling et al., 1985). Effects of overdosing with
With dermal exposures, a very small drop on the skin atropine include hyperthermia, tachycardia, inspiratory
may cause sweating and fasciculations at the site, starting stridor, irritability, and dilated and unresponsive pupils
within 18 h of exposure. A larger drop may cause loss of (Meerstadt, 1982).
consciousness, seizures, apnea and flaccid paralysis, with Pralidoxime (2-PAM) can be used to treat the nicotinic
effects beginning within 30 min (Sidell et al., 1997). signs. Pralidoxime is probably most effective when
Liquid tabun in the eye can result in death nearly as administered in the first 1 3 h. Pralidoxime is not as
quickly as an inhaled dose (EPA, 1985b). effective in the treatment of soman poisoning, due to the
On a per weight basis, toxicity in descending order is: quick “aging” (within minutes) of the compound (Sidell
VX . soman . sarin . tabun. As used, VX is the most et al., 1997). Since VX-inhibited AChE ages slowly,
potent of the “G” nerve agents and it is about three times administration of 2-PAM chloride is effective in reactivat-
more potent a respiratory agent than sarin. VX is 300 ing the enzyme for up to 48 h after exposure (Sidell and
times more lethal than tabun on skin (Sidell et al., 1997). Groff, 1974).
See Table 5.5 for LD 50 s of the various nerve agents. In Belgium, Israel, The Netherlands, Scandinavia,
Plasma cholinesterase values usually recover in a few Portugal, and Germany, obidoxime dichloride (Toxogonin,
days or weeks, due to the irreversible nature of OP inhibi- Lu ¨H-6) is the favored oxime (Jokanovi´ c, 2015). It may be
tion. RBC AChE recovers more slowly (several days to 4 a less toxic and more efficacious alternative to pralidox-
months) depending on the severity of the depression ime in poisonings from OPs containing a dimethoxy or
(Grob, 1956). Delayed neurotoxicity has not been diethoxy moiety (De Kort et al., 1988). HI-6 is an alterna-
reported in humans following nerve agent exposure. tive oxime that has excellent AChE regenerating action
However, delayed peripheral neurotoxicity has been with VX and very good action with sarin (GB). It has a
reported in animal studies. Soman, at a dose of 1.5 mg/kg, good response to soman, but needs higher doses following
produced severe delayed neuropathy in the atropinized tabun exposures (Hoffman, 1999). HI-6 is given in conjuc-
hen assay (Willems et al., 1984). No prenatal mortality or tion with atropine and diazepam (Kusic et al., 1991). A
fetal toxicity was noted in soman-poisoned rats or rabbits, treatment regime of HI-6, levetiracetam and procyclidine
even at doses producing significant maternal toxicity, but (triple therapy) works against five times the LD 50 in all
other nerve gases showed postimplantation mortality and nerve agents except tabun (Myhrer et al., 2015). Adding
fetotoxicity (HSDB, 2005; RTECS, 2006). obidoxime to the triple therapy treat tabun doses up to five
times the LD 50 Myhrer et al., 2015).
With human exposures to nerve agents, autoinjectors
Treatment
(AtroPen, Mark I, Combopen MC) are available for use.
Remove animal from the toxic environment. Administer Most available autoinjectors combine atropine and prali-
oxygen if needed. Intubation and ventilation may be nec- doxime. Autoinjectors are not used in veterinary medicine
essary if signs progress. Flush eyes with copious amounts as they are not adaptable for different sized patients.