Methoprene

Methoprene and hydroprene are first-generation juvenoids that iacorporate minor stmctural optimisation of neotenin to increase persistence. Methoprene, 1-isopropyl (E,E)-ll-methoxy-3,7,ll-tnmethyl dodecadi-2,4-enoate (129) (bp 100 C/6.7 Pa, vp 3.5 mPa at 25°C), is soluble ia water to 1.4 mg/L. The rat oral LD q is >34,000 mg/kg. Methoprene has been used as a mosquito larvicide, ia baits for ant control, and as a catde feed-through treatment for horn fly control. Hydroprene, methyl (H,H)-3,7,ll-trimethyl-dodecadi-2,4-enoate (130) (bp 174°C at 2.5 kPa, vp 2.5 mPa at 25°C), is soluble ia water to 0.54 mg/L. The rat oral LD q is >34,000 mg/kg. Hydroprene is especially effective against aphids and cockroaches. 

The use of polylactides for delivery of insect hormone analogs and other veterinary compounds (115,116) has been studied. Microspheres, pellets, and reservoir devices based on polyglycolide, poly-(DL-Iactide), poly(L-lactide), and various copolymers have been used to deliver methoprene and a number of juvenile hormone analogs. ... 

Ellgaard, E.G., J.T. Barber, S.C. Tiwari, and A.L. Friend. 1979. An analysis of the swimming behavior of fish exposed to the insect growth regulators, methoprene and diflubenzuron. Mosquito News 39 311-314. 

Lee, B.M. and G.I. Scott. 1989. Acute toxicity of temephos, fenoxycarb, diflubenzuron, and methoprene and Bacillus thuringiensis var. israelensis to the mummichog (Fundulus heteroclitus). Bull. Environ. Contam. Toxicol. 48 827-832. 

Madder, D.J. and W.L. Lockhart. 1978. A preliminary study of the effects of diflubenzuron and methoprene on rainbow trout (Salmo gairdneri Richardson). Bull. Environ. Contam. Toxicol. 20 66-70. 

Ankley, G.T., J.E. Tietge, D.L. DeFoe, K.M. Jensen, G.W. Holcombe, E.L. Durhan, and S.A. Diamond. 1998. Effects of ultraviolet light and methoprene on survival and development of Rana pipiens. Environ. Toxicol. Chem. 17 2530-2542. 

Methoprene is an insect growth regulator and it is also used as an insecticide for cockroaches. The enantioselective isomerization of 7-methoxygeranylamine in the presence of [Rh((+)-BINAP)2]+ followed by acid hydrolysis provides the intermediate, 7-methoxycitronellal, in high yield with high optical purity (97%, 98% ee, Scheme 6).9 Alternatively, methoxylation of ( -citronellalenamine (98% ee) with methanol in the presence of 97% sulfuric acid followed by hydrolysis gives 7-methoxycitronellal in 79% yield without racemiza-tion (Scheme 6).9... 

Table VII. Nonmetabolite Residues Formed on Catabolism of [5—1 l C] methoprene.

Methoprene has been fully registered since 1975 for commercial usage as a mosquito larvicide and for control of horn flies via feed-through application to cattle. In addition, methoprene is registered in Japan for administration to silkworms to enhance silk production. As the only IGR currently (July, 1978) registered, it follows that the environmental fate of methoprene has been investigated in detail. 

Reports are published on the metabolism of methoprene by plants (25), aquatic microorganisms (26), soil microbes (27), house flies and mosquitoes in vivo (28), resistant house flies in vivo and in vitro (29), a steer (30), a lactating cow (31), chickens (32), and bluegill fish (33). In addition, radioactive material balance studies have been published for a guinea pig, steer, and cow (34), chickens (35), and rats (36, 37), including whole-body autoradiography in rats (37). 

Metabolism studies of methoprene in nonaquatic organisms have provided background data which must be considered prior to discussing the fate of methoprene in aquatic systems. All nonaquatic metabolic studies reported to date have utilized [5-1 C]methoprene. The location of radiocarbon was selected both for ease of synthesis and for anticipated metabolic stability. However, studies in plants and bovines (25, 30, 31) revealed many presumed "metabolites" to be radiolabeled natural products, or "nonmetabolite residues". Primary metabolites of methoprene resulting from ester cleavage and/or (O-demethylation have been... 

Hydrolysis. Aqueous solutions of methoprene (0.5 ppm) were found to be totally stable to hydrolysis for four weeks at pH 5,... 

Photodegradation. Schaefer and Dupras (39) reported that emulsifiable formulations of methoprene at 0.1 ppm in water showed a rapid photodissipation in sunlight, whereas the commercial, microencapsulated formulation remained biologically active in water for several days under similar conditions. Aqueous solutions of methoprene undergo very rapid (t, <1 hr) photoequilibration to a mixture (,ui l) of 2E, 4E 2Z, 4E isomers (26, 39). 

The identity of methoprene photoproducts has been studied from aqueous emulsions, thin films on glass or silica gel, and in methanolic solution (Figures 3 and 4, 40). As a thin film (0.1 ym) on glass, the half-life of methoprene was about 6 hr. After 93% degradation of parent, more than 50 photoproducts were observed, only five of these present in 3% or higher yield 7-methoxycitronellic acid (4%), 7-methoxycitronellal (4%), the 4,5-epoxide of methoprene (6%), a C12 methyl ketone (3%), and 14C02 (6%). Similar products were encountered on photolysis of a 100 ppm aqueous emulsion of methoprene, except that methoxy-citronellal was isolated only as its dimethyl acetal (9% yield), a presumed artifact of work-up. In addition to the same products identified from thin film studies, at least forty-six other discrete products were detected, but not identified (40). 

In contrast, photolysis of methoprene in true aqueous solution gave a simpler distribution of different products (40). Five major products (25, 11, 13, 13, and 8% yield) were separated, but could not be positively identified due to lack of sufficient quantity (methoprene water solubility = 1.4 mg/1) and the singularly uninformative mass spectral fragmentations of the products. 

Figure 3. Photoproducts of methoprene from irradiation of an aqueous emulsion (AE) and thin film (TF)on glass (40)...

Figure 4. Methanolic photooxidation of methoprene (reaction with singlet oxygen (40)...

Figure 5. Metabolism of methoprene by soil and aquatic microorganism (26, 27)...

In summary, photodecomposition of methoprene is facile and leads to a multiplicity of products. The lower photostability in sunlight of methoprene compared to epifenonane has been mentioned previously. Because of its photochemical lability and its ready microbial degradation (see below), methoprene is microencapsulated for aquatic use as a mosquito larvicide. 

Fall has studied the capability of fourteen species of microorganisms to grow on methoprene as sole carbon source. One of these organisms, Cladosporium resinae, was able to utilize methoprene as sole carbon source, while another. Pseudomonas citronellolis, was similarly able to utilize 7-methoxycitronellic acid. (41). 

Soil microorganisms degrade methoprene rapidly and extensively (27). The hydroxy ester was isolated as a minor metabolite over 50% of the applied dose was evolved as 1 C02. Radioactivity from [5-1 0]methoprene incorporated into the humic acid, fulvic acid, and humin fractions of soil. 

Fish and Ecosystem Studies. When bluegill sunfish are exposed to a constant level of methoprene in a dynamic flowthrough system, they accumulate radiocarbon until a plateau is reached after 7-14 days (33). While levels of methoprene in fish were about lOOOx that in water at the plateau, treated bluegill placed into uncontaminated water showed a 93-95% radiocarbon reduction in 14-21 days. Analysis of fish tissues at plateau levels revealed that 90% of the radiocarbon was unmetabolized parent, 1% was the hydroxy ester, while the remainder was polar conjugates. 

The fate of methoprene was investigated in the Metcalf ecosystem (42) before the environmental lability of [5-ll,c]methoprene was documented. It seems likely that the limited data presented in that work gave spuriously high residue levels due to formation of nonmetabolite residues which interfere with the simple tic analyses performed. 

Methoprene Bluegill Metabolite pool Water Muscle 10... 

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