Soman levels in kidney and urine following administration to rat, guinea pig, and marmoset.
Concentrations of C(+/-)P(+/-)-soman (1,2,2-trimethylpropyl methylphosphonofluoridate) in urine of anaesthetized, atropinized and artificially ventilated rats, guinea pigs and marmosets were determined 1-4 h after iv administration of 1-6 LD50 of the agent and in the kidneys 1 h after iv administration of 2-6 LD50 14C-C(+/-)P(+/-)-soman. The concentrations of the toxic C(+/-)P(-)-isomers in both urine and kidneys of the rat were at least two orders of magnitude higher than the corresponding levels in the two other species. Relatively high urine concentrations were also found for C(+/-)P(+/-)-soman-intoxicated (6 LD50) rats pretreated with the nontoxic soman analogue PDP (1,2,2-trimethyl dimethylphosphinate), which considerably decreases the persistence of C(+/-)P(-)-soman in rats, or the carboxylesterase inhibitor CBDP [2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide]. The lethal effect brought about by intravesical administration of C(+/-)P(+/-)-soman in rats showed that the agent can easily be reabsorbed from the bladder. It is concluded, that this reabsorption does probably not explain the previously observed persistence and "late toxicity" of C(+/-)P(+/-)-soman in rats, although the amount of renally excreted C(+/-)P(-)-soman (ca. 1% of the administered dose) should be sufficient for a toxicologically significant effect.
de Jong
L P
LP
Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
Benschop
H P
HP
Due
A
A
Van Dijk
C
C
Trap
H C
HC
Van der Wiel
H J
HJ
Van Helden
H P
HP
D000283:Administration, Intravesical; D000818:Animals; D002144:Callithrix; D002250:Carbon Radioisotopes; D002849:Chromatography, Gas; D006168:Guinea Pigs; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D013045:Species Specificity; D013237:Stereoisomerism
D002250:Carbon Radioisotopes; D012999:Soman