Combined effects in toxicology‐a rapid systematic testing procedure: Cadmium, mercury, and lead

Abstract

A testing procedure is described for the assessment of the toxicological response (e.g., acute toxicity or mutagenicity) of any combination and number of chemical, physical, and biological agents, with no more effort for a particular combination than for a single agent. The method provides a simple, sensitive, and quantitative index of synergism, antagonism, and additivity, and it has been demonstrated experimentally in rats by determining the acute lethality of combinations of cadmium, mercury, and lead salts. In a combination of two metal salts, the dose of one metal of the pair was fixed at or near the no-effect level while the dose of the second metal was increased until the entire dose-response curve was obtained. To evaluate interactions of the three metals, the previous pair of metals were kept fixed at their combined extrapolated LD1 level, and the third metal was increased. The statistical treatment of the data employed a computer program that did not involve probit transformations, but rather the approximate linear relationship between the fractional response and the logarithm of the dose. A particular combination could be synergistic, antagonistic, or additive, depending on the relative doses employed. Generally, a combination was synergistic when the most toxic member was present at or near its LD1 dose in the presence of the much less toxic member; the same combination was protective when the least toxic member was present at or near its LD1 dose. The results clarify apparently contradictory reports regarding the biological effects of metal combinations. The application of the testing procedure to combinations of mutagens is described, and an example is cited involving, for a particular bacterial mutagen, a combination of N-methyl-N'-nitro-N-nitrosoguanidine with ethylmethanesulfonate.

Influence of zinc on cadmium induced haematological and biochemical responses in a freshwater teleost fish Catla catla

“…A one-tenth value of the LC 50 concentration of cadmium chloride for 24 h (0.669 lg) was taken as the sub-lethal concentration (Sprague 1971). The concentrations of zinc used in this study were calculated until there was no mortality and the concentration was recorded (Schubert et al 1978) at 0.3 mg/l. One tenth of this concentration (0.03 mg/l) was used for the sub-lethal studies.…”

Concentrations of Ni and V, other heavy metals, arsenic, elemental and organic carbon in atmospheric fine particles (PM2.5) from Puerto Rico

“…Although the levels of Ni and V were found to be relatively high in Guaynabo, they are comparable to the WHO (2000) report. However, one should consider the fact that the combined toxicity of metals is many times greater than the single metal (Shubert et al, 1978). Consequently, the need to analyze these individual constituents in ambient air is evident in order to incorporate such interactions in future epidemiological studies.…”

Deriving Sediment Quality Guidelines from Field-Based Species Sensitivity Distributions

“…snake-antidotes) to cause greater, equal or less effect on an organism than would be expected by the toxicity of each contaminant separately. An example of the significance of considering the effect of mixtures and chemical interactions on overall toxicity is the synergistic toxicity effects of mercury and other heavy metals (Al, Pb, Zn, Cd) in amalgams (Shubert et al, 1978): Injecting rats with LD-1 dose (i.e. the dose that is shown to kill 1 rat out of 100) of mercury and lead resulted in 100% death, and not the 1% -2% that would be expected if the combined effect of Hg and Pb was strictly additive.…”