Toxic Mixtures in Time-The Sequence Makes the Poison.

Area of Science:

• Environmental toxicology
• Ecotoxicology
• Crustacean biology

Background:

• The principle "the dose makes the poison" traditionally assumes toxic effects cease upon chemical clearance (toxicokinetic recovery).
• This overlooks toxicodynamic recovery, the re-establishment of homeostasis, which varies in speed depending on the toxicant.
• Sequential exposure to toxicants can lead to different outcomes based on exposure order.

Purpose of the Study:

• To investigate the hypothesis that the sequence of toxicant exposure influences overall toxicity.
• To determine if toxicodynamic recovery rates impact toxicity in sequential exposures.
• To assess the implications for ecological risk assessment.

Main Methods:

• Experiments were conducted on the freshwater crustacean Gammarus pulex.
• Organisms were exposed to pairs of four different toxicants (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride) with varying exposure orders.
• Toxicity was assessed by comparing outcomes from reversed exposure sequences while maintaining constant doses.

Main Results:

• Significantly different toxicity levels were observed when the order of toxicant exposure was reversed.
• Slow toxicodynamic recovery led to "carry-over toxicity" in subsequent exposures, demonstrating a sequence effect.
• This effect was contingent on toxicodynamic recovery being slow relative to the time interval between exposures.

Conclusions:

• Toxicant exposure sequence, not just dose, significantly impacts toxicity.
• Carry-over toxicity, influenced by toxicodynamic recovery, is a critical factor in sequential exposures.
• Current ecological risk assessment methods may underestimate risks by not accounting for exposure sequence and toxicodynamic recovery.