Extremely toxic phosphorothioc acid derivative are intraperitoneally injected [in the abdomen] about 400 mg/kg body weight, about 65% of the median lethal doses. The injections are to be made 4 hours before irradiation. Control subjects [injected but not irradiated] - exhibited the following acute toxic responses: nausea, vomiting, uncontrolled diarrhea, vertigo, cramps, hypotensions, etc. These effects are identical to the initial (prodromal) effects of radiation. Clinical studies [l981 - 1983] demonstrated "significant" WR-2721 mediated parathyroid hormone inhibition with hypocalcemia and calciuria - with calcium levels decreasing 20%.
Other pathological manifestations caused by this agent are: distal parathesia, capalpedal spasms etc. In multi-dose studies: severe allergenic reactions were observed. More than 50% of the male volunteers were functionally non-operational with persistent vomiting and consequently withdrew from the study. In a carefully designed studies [Bogo et al., l985] reported:
(1) WR - 2721 is behaviorally toxic at doses relevant to radioprotection.
(2) WR - 2721 treatment along with the stress of motor performance may combine to lower the level at which lethalities occur.
(3) WR - 2721 does not protect for radiation-induced PD.
(4)WR - 2721 combined with radiation disrupts performance more severely that either radiation or WR -2721 alone.
Comment
The extreme toxicity of WR-compounds and the acute danger resulting from large doses was reported in 1981 - discussed in detail by Cairnie (1983 ). Yet in spite of these severe pathological injuries caused by these WR derivatives and the findings that the WR-compound produced essentially a zero radiation protective action; this project was continued for more than then ten years and sponsored more than 700 journal articles during the period of 1980 - 1990.
Question: Where was the oversight - for this expensive failed project
.Literature:
Cairnie, A.B. Adverse Effects of the Radioprotector WR2721 Radiate Res 94, 221(1983)
Glover, D, et al. Hypocalcemia and Inhibition of Parathyroid Hormone Secretion After Administration of WR - 2721 (A Radioprotective and Chemoprotective Agent). New England Journal of Medicine , 309 Nov. 10, 1983.
Bogo,V.,Jacobs, A.J., and Weiss J.F. Behavioral Toxicity and Efficacy of WR - 2721 as a Radioprotectant. Radiat Res. 104, 182 - 190 (1985).
Conklin, J.J. and Hagen,M.F. Radiation Protection in Prolonged Space Flights. Advances in Radiation Biology 13, 215 -284 (1987).
Van Beek, M.E.A.B., Doak,R.L., Sigdestad, C.P.and Grdina,D.J. Pathological Effects of the Radiation Protector WR - 151327 in Mice. Radiat. Res.124, 79 - 84 (1990).
