Induction of supernumerary larval moulting in the tobacco hornworm Manduca sexta: interaction of bisacylhydrazine ecdysteroid agonists with endogenous Juvenile Hormone

Abstract

When given in a critical dietary dose range , the insecticidal bis acylhydrazine ecdysteroid agonists RH-5849 or tebufenozide (RH-5992) cause fifth stage Manduca sexta (L.) larvae to moult to a supernumerary sixth-stage giant larva. The effect is dependent on exposure to the chemicals immediately after the previous ecdysis. Previous removal of the corpora allata does not interfere with the induction of premature moulting by RH-5849 but completely prevents the formation of supernumerary larvae. The juvenilizing effect is therefore due to the interaction of the moult-promoting effect of the ecdysteroid agonists with the high titre of endogenous Juvenile Hormone that is present just after ecdysis to the fifth stage in this insect. The ecdysteroid agonists themselves appear to have no intrinsic Juvenile Hormoneagonist properties. Sixth-stage larvae resulting from exposure to critical dietary concentrations of RH-5849 are morphologically completely larval in character. When transferred to diet without the ecdysteroid agonist, they feed normally and gain weight, growing much larger than control fifth stage insects. At the end of the supernumerary stage, they cease to feed, wander in the usual way, and form a normal pupal cuticle but then die as pharate pupae without shedding the sixth-stage larval cuticle.

Release of chitobiase as an indicator of potential molting disruption in juvenile Daphnia magna exposed to the ecdysone receptor agonist 20-hydroxyecdysone

“…Acute (48h) exposure to 500 nM 20E was also demonstrated to cause complete inhibition of molting in adult female D. magna (Sumiya et al, 2014). In addition, similar molting defects have been frequently reported in various insects after exposure to EcR agonists (Retnakaran et al, 2003;Reynolds et al, 2009;Gelbic et al, 2011). These evidences taken together suggest that the ED effects of 20E on molting were likely the causes of lethality.…”

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

“…Organisms exposed to these EcR agonists fail to shed their old exoskeletons during molting (i.e., incomplete ecdysis; event 990) and suffer from increased mortality (event 351) as a result of a combination of physiological abnormalities and reduced feeding. This molting defect-associated AO has been widely reported in insects such as the spruce budworm (Choristoneura fumiferana), cotton leafworm (Spodoptera littoralis), and tobacco hornworm (Manduca sexta) [14,25,28] and occasionally reported in crustaceans such as the water flea (Daphnia magna), crab (Rhithropanopeus harrisii), and barnacle (Balanus amphitrite) [29,30] for both endogenous (e.g., 20E) and exogenous (e.g., TEB) EcR agonists. Individual mortality may potentially affect the population size and ultimately cause population decline.…”

Ecdysone Receptor Agonism Leading to Lethal Molting Disruption in Arthropods: Review and Adverse Outcome Pathway Development

“…Oral administering of 0.00001–10 ppm TEB to the African cotton leafworm ( Spodoptera littoralis ) resulted in incomplete molting of the old larval cuticle and death . Dietary exposure of the larval tobacco hornworm M. sexta to RH-5849 failed to shed the sixth-stage larval cuticle and died as pharate pupae . In crustaceans, acute (48h) exposure of female D. magna to 500 nM 20E led to complete molting inhibition in 66% of the test animals .…”

“…226 Dietary exposure of the larval tobacco hornworm M. sexta to RH-5849 failed to shed the sixth-stage larval cuticle and died as pharate pupae. 227 In crustaceans, acute (48h) exposure of female D. magna to 500 nM 20E led to complete molting inhibition in 66% of the test animals. 24 The histological analysis in the same study further revealed that both old and new cuticles were present in the treated animals.…”