pharmacological intervention to prevent death. Although these studies enable researchers to deduce with some certainty what organ systems will not be affected by low levels of sarin (i.e., those systems that are not affected by large doses), they are not useful in distinguishing between primary damage caused by sarin and secondary damage caused by hypoxic events following convulsions.

Acute Toxicity

In animals, sarin is acutely toxic and fatal in microgram quantities in a matter of minutes. There is some variability depending on the species and the route of administration. Table 5.3 outlines the doses and routes of administration that produce acute lethality (within 24 hours) in the animal species tested. The LD50 in the rat and mouse are similar, with subcutaneous (s.c.), intramuscular, and intravenous doses requiring 150–180 μg/kg. Oral administration requires nearly 10 times more sarin. The hen, guinea pig, and cat are more sensitive than rats and mice, with lethal doses ranging from 16–40 μg/kg s.c. to 561 μg/kg oral.

The immediate cause of death from sarin poisoning is respiratory arrest (Rickett et al., 1986). In baboons, sarin administered to the upper airway in vapor form (30 μg/kg) causes apnea within 5 minutes (Anzueto et al., 1990). Since the dose was twice the LD50, mechanical ventilation was needed to keep the animals alive. Their apnea was correlated with the absence of activity in the phrenic nerve (which projects to the diaphragm), suggesting a central effect of sarin on respiration. Respiration recovered spontaneously within 1–2 days, al-

TABLE 5.3 Acute Lethality of Sarin Administered to Various Species

Species, Strain

Route

LD50 (μg/kg)

Reference

Rat

s.c.

158–165

Landauer and Romano, 1984; Singer et al., 1987; Somani, 1992

Mouse, CD-1

s.c.

160–170

Clement, 1991

Mouse

i.m.

179

Somani, 1992

Mouse

i.v.

109

Little et al., 1986; Tripathy and Dewey, 1989

Mouse, Swiss albino

inhalation

600 mg/min/m3

Husain et al., 1993

Hen

oral

561

Bucci et al., 1993

Hen

s.c.

16.5–16.7a

Gordon et al., 1983

Guinea pig

s.c.

53 (divided doses)

Fonnum and Sterri, 1981; Somani, 1992

Cat

s.c.

30–35

Goldstein et al., 1987

NOTE: i.m. = intramuscular; i.v. = intravenous; s.c. = subcutaneous.

aConverted from 0.119 μmol/kg in Ross white or Light Sussex hens.



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