Formamidines mites

Formamidines comprise a small group of promising insecticides. Chlordimeform, formetanate, and amitraz are examples of this group. These compounds are effective against most stages of mites and ticks. Thus they am classified as ovicides, insecticides, and acariddes. Formulations are emulsifi-able concentrates and water-soluble powders. 

Formamidine effects on twospotted spider mites, Tet-ranychus urticae, included elicitation of walk-off and spin-down dispersal and reduction of fecundity and egg hatch. Formamidine-induced walk-off and spin-down were not correlated, but the former was significantly associated with formamidine-induced lethality. A moderately strong correlation existed among the activities of formamidines in reducing fecundity, egg hatch, and reproductive potential, whereas only weak associations were found between these parameters and formamidine-induced lethality. 

These results suggest that the mechanism(s) involved in formamidine-induced lethality and walk-off in mites may be similar, but other mechanisms possibly are involved in formamidine-induced spin-down and reduction of fecundity and egg hatch. 

The formamidine acaricides and insecticides, chlordimeform and ami-traz, are lethal to all life stages of acarines, but their activity to insects is considerably more restricted (1). Using the southern cattle tick, Boophilus microplus, and the twospotted spider mite, Tetranychus urticae, the structural requirements of formamidines for lethality have been elucidated ( -5), an< t ie structure (lethal moiety) for maximum activity is shown in Figure 1. Briefly, the ring must contain two substituents, and they must be located at positions two and four maximum activity was observed when position... 

The effects of 15 formamidines on twospotted spider mite dispersal behavior are given in Table I. Compounds are ranked in order of their decreasing activity as elicitors of total dispersal... 

Table I. Effects of Formamidines on Twospotted Spider Mite Dispersal Behavior3...

In a study of arylthioformamidine-mediated dispersal in the twospotted spider mite (8) and the carmine spider mite, Tetrany-chus cinnabarinus (9), it was concluded that walk-off was a function of the formamidine portion of the molecule, whereas spin-down was a function of the thiophenyl moiety. The present study (18) corroborates this conclusion. 

A dispersal and mortality correlation matrix for formamidines and spider mites is given in Table II. Total dispersal was correlated with walk-off and spin-down, but the former clearly was the major component. Total dispersal also was correlated with mortality. However, spin-down was not correlated with walk-off or with mortality. Walk-off was correlated with mortality (18). 

The procedures for examining the effects of formamidines on twospotted spider mite reproduction were similar to those for dispersal mentioned above with the following exception. After the treated leaflets had dripped dry, the surviving mites were transferred to untreated leaf discs. This initial transfer was made to minimize potential residual activity and to ensure that formamidine effects on reproduction were due to the treatment applied to the adult female mites. Under these conditions, there should be little, if any, direct ovicidal action or mortality of... 

Figure 2. Cumulative percentage spin-down by twospotteu spider mites exposed to formamidines at a concentration of 500 ppm. (Reproduced with permission from ref. 18. Copyright 1984 Entomological Society of America.) Continued on next page.

In these studies, the activity of 105 formamidines, two form-anilides, and two anilines on mite fecundity and egg hatch was investigated. With regard to fecundity, 82 compounds yielded a significant effect. Sixty-three compounds reduced fecundity at one or both concentrations 54 of these remained effective in reducing egg production for as long as or by 72 hours posttreatment. Eight compounds increased fecundity, while one formamidine was stimulatory at the low concentration and inhibitory at the high concentration (19). 

Table III. Ranking of Formamidines in Order of Their Decreasing Potencies as Inhibitors of Twospotted Spider Mite Egg Production at Seventy-two Hours Posttreatment...

The weak activity of 52 (chlordimeform) and 104 (amitraz) as reproduction inhibitors in individual mites was surprising. Of the 109 compounds examined, the rank order for inhibition of reproductive potential at 500 ppm at 72 hours was 50 for formamidine 52 (chlordimeform) it yielded 11.7%, 5.6% and 16.6% reduction of... 

To explore this further, a demographic study was conducted with chlordimeform, amitraz, and compound 17, which was the most active mite reproduction inhibitor among the nonlethal formamidines (20). Each of the three formamidines caused a reduction in survivorship and fecundity which resulted in a significant decrease in the intrinsic rate of increase of the mite population. In these experiments, amitraz was most potent, chlordimeform was intermediate, and compound 17 was least potent (20). This apparent disparity between the strong activity of chlordimeform and amitraz on mite reproduction at the population level and their weak activity at the individual level can be explained as follows. The effects of amitraz on population growth were due mainly to its lethal activity to the various life stages, and the effects of chlordimeform were due to its lethality to life stages as well as its reduction of fecundity. The activity of compound T7 resulted only from its reduction of fecundity (20). 

Since the demonstration by Knowles and co-workers (5,24-26) that the lethal action of chlordimeform in southern cattle tick larvae was due to its N-demethyl metabolite which was formed by oxidative N-dernethylation, there has been considerable interest relative to the actual compound(s) responsible for the lethal and sublethal actions of formamidines in mites. With regard to lethality, chlordimeform and demethylchlordimeform were approximately equitoxic to the twospotted spider mite (3), the Kanzawa... 

In the case of dispersal, chlordimeform, amitraz, and U-44193 and their metabolites with the formamidine moiety were active, whereas their respective formanilide and aniline metabolites were inactive (Table I). It is apparent that conversion of chlordimeform and amitraz to demethylchlordimeform and BTS-27271, respectively, would result in the formation of metabolites that are more active than the parent formamidines as elicitors of dispersal behavior in mites, but whether this conversion is required for activity remains to be demonstrated. U-44193 was appreciably more active in eliciting dispersal behavior than was BTS-27271 as the EC q values listed above and the data in Table I indicate. This may be related at least in part to the fact that U-44193 is a labile molecule and that conversion of U-44193 to BTS-27271 yields two molecules of the latter per molecule of the former (see below). Since some parent formamidines that apparently do not degrade to formamidine metabolites (e. ., formamidines 95 and 96) also elicited dispersal behavior (18), dispersal activity must be due at least in part to the parent compound and not exclusively to a metabolite. 

Mechanisms Associated with Formamidine Actions in Mites... 

Direct evidence for the mechanisms of these toxic actions of formamidines in mites is lacking. This is primarily a consequence of the limited knowledge of mite neurochemistry and physiology. 

These in vitro and in vivo investigations indicate that chlordimeform as well as other formamidines and formanilides can interfere with biogenic amine regulatory mechanisms in bulb mites. Whether these actions are related to any of the formamidine effects on mite dispersal and reproduction remains to be demonstrated. 

Figure 3. Inhibition of 2-phenylethylamine degradation in bulb mite homogenates by chlordimeform and its formamidine metabolites Homogenate and substrate concentrations were 15 mg/ml and 1 x 10 M, respectively. Points are means (n 3). Redrawn with permission from Ref. 23. Copyright 1985, Society of Chemical Industry.

The studies discussed herein show that formamidines without the conventional lethal moiety can elicit dispersal behavior and can interfere with reproduction in twospotted spider mites. Walk-off dispersal elicited by formamidines was correlated with formamidine-induced mortality. Since these structure-activity relationships of formamidines are similar to those for pertubation of octopa-minergic transmission in insects, a similar mechanism could be involved in these actions in mites. Since structure-activity relationships for formamidine effects on spin-down and reproduction were not correlated with those for lethality, other mechanisms, which may or may not involve octopamine or other biogenic amines, are probably associated with these actions. 

Chlorphenamidine has mainly an ovicidal action, but it acts in all the developmental stages of mites. In plant tissues it can be moderately translocated. Its acute oral for rats is 33S mg/kg. The metabolites of chlorphenamidine include N -(4-chloro-2-methylphenyl) formamidine, 4 -chloro-o-formotoluidine and 4 -chloro-o-toluidine (Chang and Knowles, 1977). 

The acaricidal activity of these formamidines is based on a mechanism which is entirely different from that of the chlorinated hydrocarbons, organophosphates and carbamates. Some of them are more toxic to organophosphate-resistant mites than to organophosphate susceptible ones (Dittrich, 1969). 

---