Use of joint toxic response to define the primary mode of toxic action for diverse industrial organic chemicals

Abstract

An important aspect of understanding how multiple toxicants jointly act involves defining the primary mode of toxic action for the chemicals of interest. We have explored the use of 96‐h acute toxicity tests with juvenile fathead minnows and primarily binary chemical mixtures to define the primary acute mode of toxic action for diverse industrial organic chemicals. Our investigation mainly considered the two special cases of noninteractive joint action known as concentration (simple similar) and response (independent) addition. The different forms of joint toxicity with binary mixtures were graphically illustrated by isoboie diagrams. Designated as the mode of action‐specific reference toxicants were 1‐octanol, phenol, and 2,4‐dimtrophenol. It was observed from binary isobole diagrams that a chemical with a similar primary mode of toxic action to that of a reference toxicant would display a concentration‐addition type of joint action with the reference toxicant over the entire mixture ratio range. Dissimilar chemicals with very steep concentration‐response curves generally showed an interaction that was less‐than‐concentration additive, but consistently demonstrated a joint toxicity that was greater than predicted by the response‐addition model. The more‐than‐concentration additive and complex isoboles that are indicative of interactive toxicity were not commonly observed in our experiments.

Atrazine induction of cytochrome P450 in Chironomus tentans larvae

“…These fi ndings indicate the complex nature of the underlying mechanisms by which organ-isms tolerate exposure to mixtures of xenobiotics in their environment. Therefore, it is likely that the toxicity of a pesticide mixture is more complex than a simple "con centration addition" or a "response addition" model typically used for predicting the potential impact of mixtures in aquatic systems (Broderius et al, 1995;McCarty et al, 1992;Dawson and Wilke, 1991).…”

Effects of 2,4‐dichlorophenol on the expression of vitellogenin and estrogen receptor genes and physiology impairments in Chinese rare minnow (Gobiocypris rarus)

“…The activity of erythrocyte superoxide dismutase in human erythrocytes decreased with the increasing dose of 2,4-DCP, whereas glutathione peroxidase activity increased at about 250 ppm (Bukowska, 2003). In the former studies, the LC50 value of 2,4-DCP for fish ranged from 7.0 to 11.6 mg/L were reported (Phipps et al, 1981;Broderius et al, 1995;Kishino and Kobayashi, 1996), and the no-observed-effects concentration (NOEC) of acute toxicity in medaka was 3.3 mg/L (Kondo et al, 2005). Some studies reported that 2,4-DCP affects in vitro administration causes changes in glutathione and antioxidant enzyme activities (Bukowska et al, 2003(Bukowska et al, , 2007.…”

Acute and joint toxicity of twelve substituted benzene compounds to Propsilocerus akamusi Tokunaga

“…However, the M value of nitrobenzene combined with 1,3-methylbenzene (1.660) was highest, showing a partially additive effect ( (Table 5). According to the study of Broderius [17], concentration addition is characterized by M = 1 ± 0.2, where M < 0.8 represents synergism and M > 1.2 indicates antagonism. Thus, 31.57% of 19 substituted benzenes showed synergistic effects and additive effects, while 36.84% of these compounds showed antagonistic effects.…”