Evidence for dose-additive effects of a type II pyrethroid mixture. In vitro assessment

Area of Science:

• Toxicology
• Environmental Health
• Biochemistry

Background:

• Pyrethroid insecticides are widely used, leading to population exposure.
• Limited studies quantitatively assess dose-additive effects of pyrethroids using common toxicological mechanisms.
• Understanding pyrethroid mixture toxicity is crucial for risk assessment.

Purpose of the Study:

• To evaluate the potency and efficacy of six Type II pyrethroids in inducing nitric oxide and lipid peroxides.
• To test the hypothesis of dose additivity for mixtures of these pyrethroids in vitro.
• To identify the most sensitive human cell line for pyrethroid toxicity assessment.

Main Methods:

• Assessed concentration-responses of six pyrethroids (α-cypermethrin, cyfluthrin, λ-cyhalothrin, deltamethrin, cyphenothrin, esfenvalerate) in SH-SY5Y, HepG2, and Caco-2 cells.
• Measured nitric oxide and malondialdehyde (lipid peroxides) production.
• Tested dose additivity for equitoxic mixtures of the six pyrethroids using a dose-additive model.

Main Results:

• The human neuroblastoma SH-SY5Y cell line was the most sensitive in vitro model.
• Established a rank order of pyrethroid potency for SH-SY5Y cell viability (MTT assay): deltamethrin > cyphenothrin > λ-cyhalothrin > cyfluthrin > esfenvalerate > α-cypermethrin.
• Mixtures of the six pyrethroids at equitoxic ratios demonstrated dose-additive effects on nitric oxide and malondialdehyde production.

Conclusions:

• Pyrethroid mixtures exhibit dose-additive effects on key toxicological markers in vitro.
• The findings align with previous in vivo and in vitro studies on pyrethroid additivity.
• Supports the use of a dose-additive model for assessing pyrethroid mixture toxicity in human cells.