Effect of cyclodienes

Walker, C.H. and Newton, 1. (1998). Effects of cyclodiene insecticides on the sparrowhawk in Britain—a reappraisal of the evidence. Ecotoxicology 7, 185-189. 

Mehorta BD, Moorthy KS, Ravichandra R, et al. 1989. Effects of cyclodiene compounds on calcium pump activity in rat brain and heart. Toxicology 54 17-29. 

Researchers were also able to establish the link between declines of other predatory species such as the European sparrowhawk and the use of organo-chlorine pesticides other than DDT. For instance, the cyclodiene insecticides aldrin, dieldrin, and he-ptachlor used as seed treatments caused massive mortality of both seed-eating species and their predators. All of the insecticides had the following points in common they were highly soluble in fats and refractory to metabolism. The impacts on the predatory species typically take place in periods of food stress when fat soluble residues are released from fat stores and returned into general circulation. In a food-stressed individual, the brain remains as the most lipid rich tissue and this is where contaminants move to. Toxicity results when threshold values in brain tissue are exceeded. At sublethal levels, documented effects of cyclodiene insecticides in birds have included changes in their reproductive, social, and avoidance behaviors. 

Walker, C.H. and Newton, I. (1999) Effects of cyclodienes insecticides on raptors in Britain -correction and updating of an earlier paper. Ecotoxicology, 8, 185-189. 

Table I. Effect of cyclodienes and other agents on [ H]a-dihydropicrotoxinin binding ...

The detrimental effect of organochlorine pesticides on reproductive success in birds of prey is well established following the crash of some populations during the 1950s and 1960s. Links have been established with the DDT metabolite, DDE, the cyclodiene pesticides and Although many raptor species... 

Although eggshell thinning attributable to DDE exposure has occurred in birds in the UK, the lethal and siiblethal effects of the cyclodiene pesticides aldrin, dieldrin and heptachlor are also believed to have contributed to the population effects, particularly in the case of the sparrowhawk and peregrine falcon. Following the withdrawal of DDT and the cyclodienes from use in the UK, Europe and North America, bird of prey populations that were severely affected have shown partial or complete recovery. ... 

Balasubramaniam E, Paul V, Jayakumar AR, et al. 1996. The effect of chronic cyclodiene insecticide treatment on some pharmacological actions of diazepam in rats. Environ Toxicol and Pharm(2) 141-146. 

Experimental animals exposed to sublethal doses of cyclodienes show a similar picture, with changes in EEG patterns, disorientation, loss of muscular coordination and vomiting, as well as convulsions, the latter becoming more severe with increasing doses (Hayes and Laws 1991). It is clear from these wide-ranging studies that a number of neurotoxic effects can be caused by cyclodienes at levels well below those that are lethal. In the human studies described here, subclinical symptoms were frequently reported when dieldrin blood levels were in the range 50-100 pg/L, an order of magnitude below those associated with lethal intoxication. 

In one example (Lawrence and Casida 1984, Abalis et al. 1985) rat brain microsacs were used to test the action of cyclodiene insecticides such as dieldrin and endrin on the GABA receptors contained therein. The influx of radiolabeled CL into the microsacs via the pore channel of the receptor was inhibited by these chemicals. A similar assay was developed using microsacs from cockroach nerve. Assays with this preparation showed again the inhibitory effect of a cyclodiene (this time heptachlor epoxide) on CL influx. Also, that microsacs from cyclodiene resistant cockroaches were insensitive to the inhibitory effect of picrotoxinin, which binds to the same site on the GABA receptor (Kadous et al. 1983). 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

The most serious toxicological effect of endrin is central neurotoxicity (Klaasen et al. 1986). Organo-chlorines interfere with the normal flux of cations across the axon, disrupting central nervous system homeostasis (Finkel 1983 Klaasen et al. 1986). Endrin is one of the most toxic cyclodienes, and seizure activity may develop rapidly after exposure (Proctor et al. 1988). In most cases, recovery is rapid. However, headaches, dizziness, weakness, and anorexia may persist for 2-4 weeks. 

Heptachlor, chlordane, and endosulfan (another cyclodiene pesticide) were shown to inhibit hepatocyte gap junctional intercellular communication (Ruch et al. 1990). All three pesticides showed similar dose-response relationships. Further testing with chlordane and heptachlor indicated that inhibition of the cytochrome P-450 system had no effect on this response. These results suggest that the interference with intercellular communication is not directly tied into the effects of these cyclodienes on the P-450 system. 

Early studies of cyclodienes revealed reproductive effects on mice, rats, and dogs associated with changes in the estrus cycle (ref. 100, p. 154). Ottolenghi et al. (ref. 105) observed teratogenic effects on mice and hamsters at 1/2 LD q doses of aldrin, dieldrin and endrin. In addition to the anomalies observed (cleft palate, webbed feet and open eyes), growth retardation and fetal deaths occurred. Effects on the dams were not reported, but none of the expected overt toxic symptoms associated with chlorinated cycloalkenes was in evidence (ref. 105) ... 

Similarly, a report produced by the NHMRC (1992) on cyclodiene insecticide use in Australia provides a summary of the toxicological and chronic health effects of aldrin, dieldrin, chlordane and heptachlor. 

Neurotoxic antifeedants from Compositae should provide important leads into strategies that ameliorate the control of the Diabrotica complex. Phytochemicals with combined effects that result in loss of insecticide resistance, reduced feeding, decreased life span, and neurotoxicity in rootworms may be a practical avenue to low chemical input strategies for com production. Also, phytochemical antagonism of cyclodiene resistance may have important consequences to future control of com rootworm by insecticides such as avermectins and pyrethroids (e.g. tefluthrin) which, certainly in the former case (121) and at least secondarily in the latter case (122), act on the GABA gated-chloride ionophore complex. 

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