γ‐Dodecalactone Produces Reversible Knockdown and Shows Increased Toxicity at Lower Temperatures in the German Cockroach

ABSTRACT The German cockroach, Blattella germanica (Linnaeus) (Blattodea: Ecotibiidae), is a cosmopolitan pest of medical and economic significance. Because this species has widespread resistance to conventional insecticides, there is an urgent need to identify alternative compounds with novel modes of action. γ‐Dodecalactone, a naturally occurring aliphatic lactone, has shown behavioral and toxic effects in various insect0s, but its potential as an insecticide against B. germanica remains unexplored. We investigated the topical toxicity of γ‐dodecalactone in adult male cockroaches, measuring knockdown and recovery under two ambient temperatures (14°C and 24°C) and with or without the synergist piperonyl butoxide. Knockdown Time 50% (KT 50 ), locomotor activity, intoxication symptoms, and cuticular absorption of γ‐dodecalactone and piperonyl butoxide were assessed. γ‐Dodecalactone induced reversible knockdown, tremors, and uncoordinated leg movements, without altering general locomotor activity. During the first min after treatment, γ‐dodecalactone did not significantly affect general locomotor activity. As intoxication progressed, tremors and uncoordinated leg movements became evident, and locomotor activity eventually ceased when knockdown occurred. Subsequently, the insects gradually recovered from knockdown. KT 50 decreased at lower temperature and with piperonyl butoxide co‐application, suggesting that oxidative metabolism modulates toxicity. Cuticular absorption was efficient, with ~20% of γ‐dodecalactone and ~40% of piperonyl butoxide recovered internally, independent of co‐application. Compared with deltamethrin, γ‐dodecalactone acted more slowly, reflecting its low inherent toxicity. Overall, our results indicate that γ ‐dodecalactone has limited insecticidal efficacy against B. germanica at the doses evaluated, as it induces reversible knockdown without causing substantial mortality. Therefore, its value does not lie in its immediate applicability as a control agent, but rather in its usefulness as a model compound to investigate temperature‐dependent toxicity, metabolic interactions, and neurophysiological effects of aliphatic lactones in insects. These findings identify γ‐dodecalactone as a bioactive substance affecting the nervous system of B. germanica and provide a basis for exploring structurally related compounds with improved insecticidal efficacy.