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Aquatic toxicity tests were undertaken to evaluate the environmental significance of hexamethylphosphoramide (HMPA), an industrial solvent which has been shown to be an animal carcinogen. Hexamethylphosphoramide's 48-h LC50 to Daphnia magna and 96-h LC50 to bluegill sunfish (Lepomis macrochirus) were 4220 mg/litre and 7420 mg/litre, respectively. In concentrations up to and including 5140 mg/litre, HMPA did not interfere with the normal development of Eastern oyster (Crassostrea virginica) embryos to the veliger stage. Both sheepshead minnows (Cyprinodon variegatus) and Eastern oysters developed concentrations of HMPA in their tissues rapidly from 0.5, 8.4, and 40.4 mg/litre treatments, with the plateau concentrations rarely exceeding the exposure concentrations. Whole-body residues peaked in about three to seven days after the initiation of exposure. Sheepshead minnows demonstrated a greater ability to metabolize HMPA than oysters, while oysters depurated HMPA and its metabolites more rapidly than fish. Both species largely eliminated HMPA and its metabolites within one day of depuration. The bioconcentration factors for fish and oysters were less than four, which suggests that HMPA does not pose a substantial environmental hazard from the standpoint of its accumulation in aquatic organisms. The oyster mortality in the 8.4 and 40.4 mg/litre treatments was appreciably greater than that in the controls, while the fish mortality was similar among all the treatments and the control.

The approach of mammalian toxicologists to determining margins of safety has been to define situational margins of safety for each definable situation; however, aquatic toxicologists have taken a global approach to estimating safety margins, attempting to establish a single margin of safety to encompass all conceivable situations. Though either approach can determine safety margins that will protect organisms or systems of concern, the global approach is likely to be more conservative, and thus much more difficult to achieve. In the future, aquatic toxicologists should try to move toward situationally dependent assessments.