Drugs

Drugs in an insect's food may cause a variety of disruptions to its development ((Introna et al. 2001); Lopes de Carvalho 2010), accelerating or extending the duration of the larval and/or puparial stages.

The effects of drugs may be species-specific. For instance, heroin (and/or its metabolite, morphine) was associated with accelerated larval growth in Sarcophaga peregrina (Robineau-Desvoidy) (Goff et al. 1991a), but morphine retarded larval growth in Lucilia sericata Meigen and C. vicina (Bourel et al. 1999). Diazepam (and/or its metabolites, nordiazepam and oxazepam) accelerated larval growth and puparial metamorphosis in C. albiceps and Chrysomya putoria (Wiedemann) (Lopes de Carvalho et al. 2001), while nordiazepam (and oxazepam) administered at lower concentrations had no effect on Calliphora vicina (Pien et al. 2004). The dose that larvae experience is complicated by drug tropism, and experimental protocols need to take into account metabolism, sequestration and excretion of the administered drug over time (Introna et al. 2001), and the effects of the metabolites. Perhaps for these reasons, some drugs' effects are restricted to only parts of development (Kharbouche et al. 2008; O'Brien and Turner 2004). It is clear that the effects of one drug do not predict those of another (Sadler et al. 1997a; Sadler et al. 1997b; Sadler et al. 1997c), but whether a drug's effects are widespread or consistent across species, whether larval responses have a phylogenetic component, and whether they are affected by temperature all need to be clarified.

The effects of drugs may bias the mean duration of development to eclosion by as much as 109 h (an underestimate of 40%) at 27°C (Lopes de Carvalho et al. 2001, 2010), but are generally much less extreme (Introna et al. 2001). The initial effects of some drugs pass off later in development (Kharbouche et al. 2008; O'Brien and Turner 2004) and development returns to schedule. Few studies have reported measures of precision, but those that do (e.g. (Lopes de Carvalho et al. 2001; Musvasva et al. 2001)) indicate a slight increase in the coefficients of variation compared to control treatments, which is expected from the addition of an extra experimental variable (the drug effect). Most entomotoxicological experiments are done under temperatures in the region of 22-27°C, which is lower than the temperatures of many natural maggot aggregations, so that the absolute error may be smaller under natural conditions and precision may improve, but it is probable that the relative error changes little. Some studies were done at slightly variable temperatures in the 22-27°C range, where blowfly development is unfortunately most sensitive to changes in temperature, and it is not clear how this affected their findings.

From a practical perspective, a direct correlation between the drug content of larvae or puparia and that of their food is generally poor or absent (Campobasso et al. 2004; Pien et al. 2004; Sadler et al. 1997a; Sadler et al. 1997b; Sadler et al. 1997c; Tracqui et al. 2004), although not always (Kharbouche et al. 2008). For this reason, when an effect is dose-dependent and the drug is not sequestered, it is currently difficult to work backwards from knowing the concentrations of drugs in larvae to applying a correction factor to the PMImn. Even if species-specific pharmacological models for each drug become available that take into account the metabolism, sequestration or excretion of drugs by larvae, and the effects of their metabolites, temperature and their interactions, they may be difficult to apply because the duration of exposure (i.e. the age of the insect) is a key unknown variable that would have to be estimated from the size of the insect. Fortunately, sophisticated statistical models have been developed (Ieno et al. 2010) that can help to improve the precision of such models and take into account the non-linearity of pharmacodynamics. The drug concentrations in the food in such situations may be irrelevant if there is significant tropism and larval migration within the corpse. However, not all effects are dose-dependent (Kharbouche et al. 2008; O'Brien and Turner 2004), and in these cases the corrections are simpler to make. In casework and experiments, sample sizes of 30 or more of the largest larvae should be measured to improve sample precision (Fig. 7.3). It is also recommended that research is directed to distinguishing the effects of drug tropism from the effects of the tissue type itself (Cardoso Ribeiro and Veira Milward-de-Azevedo 1997; Clark et al. 2006; Ireland and Turner 2005; Kaneshrajah and Turner 2004), and that particular attention is given to controlling for the confounding effects of temperature. The validation of toxicological methods is discussed in much greater detail by (Peters et al. 2007).

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