Avermectins: Biological and Pesticidal Activities - American Chemical

Chapter 7

Avermectins: Biological and Pesticidal Activities

Downloaded by UNIV OF CALIFORNIA SAN DIEGO on April 4, 2016 | http://pubs.acs.org Publication Date: November 28, 1988 | doi: 10.1021/bk-1988-0380.ch007

J. R. Babu Agricultural Research and Development, Merck Sharp & Dohme Research Laboratories, Three Bridges, NJ 08887

The avermectins, which show highly potent, broad spectrum of activities against plant parasitic mites, insects and nematodes were discovered in a screening program for natural products of microbial origin. The successful characteristics of this program are discussed. The GABAergic mode of action of the avermectins is unique. Other novel biological properties include: rapid photodegradation of foliar surface deposits, translaminar activity which maintains a pesticidal reservoir within the leaf; sublethal effects on organisms, such as debilitated feeding and reduction in fecundity; and virtual immobility and microbial decomposition in soil. The d i s c o v e r y o f t h e a v e r m e c t i n f a m i l y o f m a c r o c y c l i c l a c t o n e s produced by t h e s o i l a c t i n o m y c e t e Streptomyces a v e r m i t i l i s marks an i n s t r u c t i v e c h a p t e r i n t h e search f o r n a t u r a l p r o d u c t s o f m i c r o b i a l o r i g i n . They were not found i n a g e n e r a l i z e d , broad spectrum s c r e e n , but i n one which had demonstrable elements o f r a t i o n a l e and s p e c i f i c o b j e c t i v e s . In d i s c u s s i n g t h e c h a r a c t e r i s t i c s o f t h e s u c c e s s f u l s c r e e n i n g program which l e d t o t h e d i s c o v e r y o f t h e a v e r m e c t i n s a t t h e Merck Sharp and Dohme Research L a b o r a t o r i e s , Campbell e t c H . [1) p o i n t out t h a t t h e d i s c o v e r y " . . w a s by no means s e r e n d i p i t o u s ; those who were s e e k i n g found what they s o u g h t " . T h e i r account and those o f S t a p l e y and Woodruff (2) and Woodruff and Burg (3) g i v e t h e d e t a i l s o f t h e i n i t i a t i o n and o r g a n i z a t i o n o f t h e s c r e e n i n g e f f o r t s and t h e i r denouement as t h e a v e r m e c t i n s . c

0097-6156/88/0380-0091$06.00/0 1988 American Chemical Society

Cutler; Biologically Active Natural Products ACS Symposium Series; American Chemical Society: Washington, DC, 1988.


BIOLOGICALLY ACTIVE NATURAL PRODUCTS The a v e r m e c t i n s were d i s c o v e r e d i n an a n t h e l m i n t i c s c r e e n i n g program i n which m i c r o b i a l f e r m e n t a t i o n b r o t h s were t e s t e d i n mice a g a i n s t the nematode Nematospiroides d u b i u s . Two c h a r a c t e r i s t i c s o f t h i s s c r e e n i n g program a r e worth mentioning. F i r s t , instead of i n v i t r o , " r a t i o n a l i s t " t e s t s such as t a r g e t enzyme i n h i b i t i o n o r r e c e p t o r b i n d i n g , the f e r m e n t a t i o n b r o t h s were t e s t e d by being a d m i n i s t e r e d i n d i e t t o n e m a t o d e - i n f e s t e d m i c e ; even though such an HI v i v o approach was e x p e n s i v e , i t s i m u l t a n e o u s l y t e s t e d f o r e f f i c a c y a g a i n s t a p a r a s i t e and t o x i c i t y t o the h o s t , which c o n t r i b u t e d t o the speed o f f u r t h e r work on t h e a c t i v e entities. Second, a d e l i b e r a t e c h o i c e was made t o emphasize t h e s e l e c t i o n o f microorganisms o f unusual m o r p h o l o g i c a l t r a i t s and n u t r i t i o n a l r e q u i r e m e n t s (2). Indeed, the c u l t u r e s o f S. a v e r m i t i l i s have c h a r a c t e r i s t i c s which i n c l u d i n g b r o w n i s h - g r e y spore masses, smooth spore s u r f a c e , sporophores f o r m i n g compact t o s l i g h t l y open s p i r a l s and presence o f m e l a n o i d pigments are u n l i k e t h o s e o f any other p r e v i o u s l y described species of Streptomyces. Burg e t a K £4) have g i v e n the taxonomic d e s c r i p t i o n and the f e r m e n t a t i o n procedures f o r S. a v e r m i t i l i s .

Among the a v e r m e c t i n s , a v e r m e c t i n B,, and t o a l e s s e r e x t e n t a v e r m e c t i n B« , have been s t u d i e d w i t h r e f e r e n c e to p l a n t p a r a s i t i c m i t e ? , i n s e c t s and nematodes. S i n c e the i n t r o d u c t o r y summary by P u t t e r e t £5), l i m i t e d review o f the a g r i c u l t u r a l m i t i c i d a l and i n s e c t i c i d a l a c t i v i t i e s o f a v e r m e c t i n B. has been p u b l i s h e d by Dybas and Green £ 6 ) . More r e c e n t l y , S t r o n g and Brown £7) have c o m p i l e d a comprehensive r e v i e w o f the l i t e r a t u r e on the a g r i c u l t u r a l and v e t e r i n a r y i n s e c t i c i d a l a c t i v i t i e s o f the a v e r m e c t i n s . In the c o n t e x t o f t h i s symposium, I i n t e n d t h i s a r t i c l e not as a comprehensive r e v i e w but as a way o f d i s c u s s i n g some o f t h e unique b i o l o g i c a l p r o p e r t i e s o f the a v e r m e c t i n s i n r e l a t i o n t o t h e i r a c t i v i t i e s a g a i n s t nematodes, m i t e s and i n s e c t s of a g r i c u l t u r a l importance. a

C h e m i s t r y and Nomenclature The a v e r m e c t i n s comprise a complex o f 8 d i s c r e t e but c l o s e l y r e l a t e d m a c r o c y c l i c l a c t o n e s . W i t h i n t h i s complex t h e r e are f o u r major components — a v e r m e c t i n s A- , A , B, and B and f o u r minor homologous b " components-A,. , A«. , B,. ana Bpu. M i x t u r e s o f the homologous substances c o n t a i n i n g a p p r o x i m a t e l y 80% or more o f the " a " and 20% o r l e s s o f t h e c o r r e s p o n d i n g " b " components are u s u a l l y r e f e r r e d t o as a v e r m e c t i n A p a v e r m e c t i n B^, a v e r m e c t i n A , and a v e r m e c t i n B . 2

H

2

2


2

BABU



A composite s t r u c t u r e o f the a v e r m e c t i n s i s g i v e n i n F i g u r e 1. I t c o n s i s t s o f a r i g i d 16-membered l a c t o n e r i n g system, a s p i r o k e t a l f o r m i n g two 6-membered r i n g s , and a c y c l o h e x e n e d i o l o r methoxycyclohexenol c i s - f u s e d t o a five-membered c y c l i c e t h e r . In a d d i t i o n , the s t r u c t u r e s are c h a r a c t e r i z e d by a d i s a c c h a r i d e s u b s t i t u e n t c o n s i s t i n g o f two i d e n t i c a l monomers, a l p h a - L - o l e a n d r o s e , c o u p l e d t o carbon-13 through an oxygen bond. The l a r g e "A" d e s i g n a t i o n r e f e r s t o t h e a v e r m e c t i n components i n which a methoxy group i s p r e s e n t a t C-5 and the l a r g e " B " r e f e r s t o the c o r r e s p o n d i n g C-5 hydroxy a n a l o g . The s u b s c r i p t " 1 " i s used t o i d e n t i f y those components w i t h a 22,23-double bond. The s u b s c r i p t " 2 " i d e n t i f i e s those components w i t h a 2 3 - h y d r o x y l group. Both " A " and " B " s e r i e s o f components a r e f u r t h e r c h a r a c t e r i z e d by the presence o f a s e c o n d a r y - b u t y l s u b s t i t u e n t i n the 25-carbon p o s i t i o n , w h i l e t h e minor homolog c o n t a i n s an i s o p r o p y l s u b s t i t u e n t . D e t a i l s o f the s t e p s l e a d i n g t o the e l u c i d a t i o n o f the s t r u c t u r e s o f t h e a v e r m e c t i n s have been p u b l i s h e d e a r l i e r (8,9). F i s h e r and M r o z i k [10) g i v e a comprehensive r e v i e w o f the c h e m i s t r y o f the a v e r m e c t i n s and o f a complex o f 13 c l o s e l y r e l a t e d compounds known as m i l b e m y c i n s which were i s o l a t e d from S. h y g r o s c o p i c u s by Japanese r e s e a r c h e r s ( 1 1 , 12, 1 3 ) . A n o t a b l e d i f f e r e n c e a v e r m e c t i n s i s the absence o f the 13-hydroxy d i s a c c h a r i d e s u b s t i t u e n t and s a t u r a t i o n a t the 2 2 , 2 3 - p o s i t i o n s i n a l l the r e p o r t e d m i l b e m y c i n compounds. A n o t h e r major d i f f e r e n c e i s t h e presence o f methyl and e t h y l groups a t t a c h e d t o C-25 o f the milbemycins w h i l e the a v e r m e c t i n s have secondary b u t y l and i s o p r o p y l groups. W h i l e the a v e r m e c t i n s as a c l a s s are a c t i v e a g a i n s t nematodes, i n s e c t s , m i t e s and o t h e r a r t h r o p o d s , they show d i f f e r e n c e s i n terms o f degrees o f a c t i v i t y (6). Components o f the " B " s e r i e s are more b i o l o g i c a l l y a c t i v e than t h o s e o f the "A" s e r i e s . Among the " B " s e r i e s , a v e r m e c t i n B, ( c o n t a i n i n g 80% or more o f a v e r m e c t i n B, and 20% o r l e s s of a v e r m e c t i n B^. ) has been p r e d o m i n a n t l y s t u d i e d as an a g r i c u l t u r a l a c a r i c i d e and i n s e c t i c i d e . A v e r m e c t i n B« , and i t s s o i l m e t a b o l i t e known as a v e r m e c t i n B 2 - 2 3 - k e t o n e nave a

been s t u d i e d f o r t h e i r s o i l n e m a t i c i d a l a c t i v i t i e s . A s y n t h e t i c d e r i v a t i v e o f a v e r m e c t i n B*, 2 2 , 2 3 - d i h y d r o a v e r m e c t i n B,, known by the g e n e r i c name i v e r m e c t i n has been developed f o r v e t e r i n a r y and human h e a l t h uses (14, 15, 16, 1 7 ) . The word "ABAMECTIN' has been a c c e p t e d as the n o n p r o p r i e t a r y common name f o r a v e r m e c t i n B, [18, 1 9 ) . It is c u r r e n t l y marketed as A v i d and V e r t i m e c which are the t r a d e


94

BIOLOGICALLY ACTIVE NATURAL PRODUCTS


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AVERMECTIN

A

:

R

1

:

X =

5

=

B

OCH3

:

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s

= OH OH

-CH=CH-

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^25

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2 a

:

X =

-CHo-CH-

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IVERMECTIN

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X = -CH -CH -

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23-KET0NE

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^25

2

2

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AND

2

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AND

F i g u r e 1: S t r u c t u r e s o f t h e a v e r m e c t i n s ( C o u r t e s y o f H. M r o z i k , Merck and C o . , I n c . ) .


N

^

BABU



names f o r an e m u l s i f i a b l e c o n c e n t r a t e c o n t a i n i n g 1.8% w/v o f abamectin f o r use a g a i n s t p l a n t p a r a s i t i c m i t e s and i n s e c t s i n a g r i c u l t u r e . A f f i r m i s the t r a d e name f o r a b a i t f o r m u l a t i o n c o n t a i n i n g 0.011% w/w o f abamectin f o r use a g a i n s t the red imported f i r e ant S o l e n o p s i s i n v i c t a . I t i s a l s o used as a c a t t l e a n t h e l m i n t i c and e c t o p a r a s i t i c i d e as a 1% w/v i n j e c t a b l e under the t r a d e name Avomec i n A u s t r a l i a . E a r l y p h a r m a c o l o g i c a l , b i o p h y s i c a l and b i o c h e m i c a l s t u d i e s used s e v e r a l a v e r m e c t i n s such as a v e r m e c t i n EL, the B, component a l o n e and i v e r m e c t i n £ 2 0 ) . O b s e r v a t i o n s from these s t u d i e s and the s t r u c t u r e - a c t i v i t y r e l a t i o n s h i p s (10) show t h e r e i s no e v i d e n c e f o r q u a l i t a t i v e d i f f e r e n c e s i n the mode o f a c t i o n o f the a v e r m e c t i n s . Therefore, in this d i s c u s s i o n , the word ' a v e r m e c t i n s ' w i l l be used as a g e n e r i c reference. Mode o f A c t i o n E a r l y o b s e r v a t i o n s on the s e l e c t i v e b i o l o g i c a l a c t i v i t i e s o f t h e a v e r m e c t i n s were i n s t r u m e n t a l i n u n d e r s t a n d i n g t h e i r mode o f a c t i o n . W h i l e showing s t r o n g a n t h e l m i n t i c , i n s e c t i c i d a l and a c a r i c i d a l a c t i v i t i e s , they were i n e f f e c t i v e a g a i n s t P l a t y h e l m i n t h s such as f l u k e s and tapeworms. Avermectins were a l s o i n a c t i v e a g a i n s t b a c t e r i a , y e a s t s and p r o t o z o a . An e a r l i e r r e p o r t t h a t a methanol e x t r a c t o f a c u l t u r e o f S. a v e r m i t i l i s i n h i b i t e d some f i l a m e n t o u s f u n g i by i n t e r f e r i n g w i t h c h i t i n b i o s y n t h e s i s £21) has been proved t o be erroneous by O n i s h i and M i l l e r £22) who showed t h a t o l i g o m y c i n (23) and an a n t i f u n g a l polyene produced by the organism accounted f o r t h e a n t i f u n g a l a c t i v i t y and t h a t pure a v e r m e c t i n B, d i d not a f f e c t the f u n g i o r t h e i r c h i t i n m e t a b o l i s m . Similarly, Gordnier et (24) have been unable t o d e t e c t i n h i b i t i o n o f c h i t i n a s e or c h i t i n s y n t h e t a s e d e r i v e d from a v a r i e t y o f insects. Thus the c o n c l u s i o n was t h a t t h e r e must be a s p e c i f i c t a r g e t f o r t h e a v e r m e c t i n s ' a c t i v i t y i n nematodes and a r t h r o p o d s which i s e i t h e r absent o r i n a c c e s s i b l e i n f u n g i , b a c t e r i a , and P l a t y h e l m i n t h s . Wang £25) g i v e s an e x c e l l e n t , p r o t a g o n i s t ' s account o f t h e e f f o r t s wfiich l e d t o the c o n c l u s i o n t h a t the a v e r m e c t i n s a c t on i n v e r t e b r a t e s by p o t e n t i a t i n g the a c t i v i t y o f gamma-aminobutyric a c i d (GABA) which i s an i n h i b i t o r y n e u r o t r a n s m i t t e r i n t h e i r nervous systems. Wright £20) g i v e s a comprehensive r e v i e w o f the work done on u n d e r s t a n d i n g the mode o f a c t i o n o f the a v e r m e c t i n s and S t r e t t o n e t al_. £16) have reviewed the mode o f a c t i o n w i t h s p e c i f i c r e f e r e n c e t o nematodes. Since a d e t a i l e d a n a l y s i s o f the work done t o understand the mode o f a c t i o n i s out o f the scope o f t h i s a r t i c l e , I w i l l p r o v i d e a summary o f the c u r r e n t knowledge on the mode o f a c t i o n i n r e l a t i o n t o the observed b i o l o g i c a l a c t i v i t i e s .



BIOLOGICALLY ACTIVE NATURAL PRODUCTS E l e c t r o p h y s i o l o g i c a l r e s e a r c h done soon a f t e r the d i s c o v e r y o f the a v e r m e c t i n s w i t h the nematode A s c a r i s (26) and the c r u s t a c e a n a r t h r o p o d l o b s t e r £27) showed t h a t a v e r m e c t i n s f u n c t i o n e d as p o s t - s y n a p t i c a g o n i s t s o f GABA, p o t e n t i a t i n g t h e GABA-mediated c h l o r i d e i o n channel conductance. C o r o l l a r y work £28) demonstrated t h a t a v e r m e c t i n s markedly s t i m u l a t e d the r e l e a s e o f GABA from r a t b r a i n synaptosomes which had been p r e l o a d e d w i t h r a d i o l a b e l e d GABA. F u r t h e r work on the GABA-receptor p r e p a r a t i o n s d e r i v e d from mammalian b r a i n ( 2 8 , 29) showed t h a t a v e r m e c t i n s b i n d t o GABA-receptors and a l s o i n c r e a s e d t h e a f f i n i t y o f these r e c e p t o r s f o r benzodiazepams £ 3 0 ) . It i s a l s o known t h a t GABA i t s e l f a l s o s t i m u l a t e s the b i n d i n g o f benzodiazepams t o the GABA-receptors £ 3 1 ) . S i n c e both GABA and the a v e r m e c t i n s s t i m u l a t e benzodiazepam b i n d i n g , one can i n f e r t h a t a v e r m e c t i n s , l i k e GABA, open the c h l o r i d e channel o f the GABA-receptor and thus a v e r m e c t i n s behave as GABAergic agonists. T h e r e f o r e , w i t h r e f e r e n c e t o nematodes and i n s e c t s , t h e c u r r e n t e x p l a n a t i o n f o r the mode o f a c t i o n i s t h a t a v e r m e c t i n s s t i m u l a t e the r e l e a s e o f GABA from nerve endings and then enhance the b i n d i n g o f GABA t o r e c e p t o r s i t e s on the p o s t s y n a p t i c membrane of an i n h i b i t o r y motoneuron i n the case o f nematodes, and on the p o s t - j u n c t i o n membrane o f a muscle c e l l i n the case o f i n s e c t s and o t h e r a r t h r o p o d s . The enhanced GABA-binding r e s u l t s i n an i n c r e a s e d f l o w o f c h l o r i d e i o n s i n t o the c e l l w i t h consequent h y p e r p o l a r i z a t i o n and e l i m i n a t i o n o f s i g n a l t r a n s m i s s i o n . An i n d i r e c t y e t s t r o n g e v i d e n c e t h a t GABA p l a y s a r o l e i s t h a t the e f f e c t s o f a v e r m e c t i n s on i n v e r t e b r a t e s can be r e v e r s e d by the c h e m i c a l s p i c r o t o x i n o r b i c u c u l l i n e £32) which a c t as GABA-antagonists by s l i g h t l y d i f f e r e n t mechanisms £ 3 3 , 3 4 ) . Picrotoxin n o n c o m p e t i t i v e ^ antagonizes GABA(35), while b i c u c u l l i n e c o m p e t i t i v e l y a n t a g o n i z e s by d i s p l a c i n g GABA from the b i n d i n g s i t e s on the r e c e p t o r ( 3 6 ) . W h i l e the GABAergic mechanism has been l a r g e l y a c c e p t e d , t h e r e are a l s o i n d i c a t i o n s t h a t a v e r m e c t i n s have more than one mode o f a c t i o n . A t l e a s t two d i s t i n c t s i t e s o f a c t i o n , d i f f e r i n g i n t h e i r l o c a t i o n , p h a r m a c o l o g i c a l b e h a v i o r or b o t h , have been r e c o g n i z e d i n a r t h r o p o d s £ 3 7 , 38) and nematodes £ 2 6 , 3 9 ) . S t r e t t o n et a K £16) c o n c l u d e : "Whether there s y s t e m , and whether the two s i t e s are comparable i n d i f f e r e n t p h y l a (Nematoda and A r t h r o p o d a ) i s not c l e a r . A common t h r e a d i n many cases i s t h a t t h e r e are c o r r e l a t i o n s between AVM ( s i c ) s e n s i t i v e l o c i and the presence o f (gamma)-aminobutyric a c i d (GABA) s e n s i t i v e mechanisms i n v o l v i n g a c h l o r i d e i o n p e r m e a b i l i t y change".


BABU


A c t i v i t y Against Soil

Nematodes

The b i o l o g i c a l a c t i v i t i e s o f the a v e r m e c t i n s on p l a n t p a r a s i t i c nematodes have m o s t l y been s t u d i e d i n terms o f t h e i r gross e f f e c t s on the movement and i n f e c t i v e b e h a v i o r o f the j u v e n i l e s o f the r o o t k n o t nematodes Meloidogyne spp. J u v e n i l e s o f M. i n c o g n i t a exposed t o a 120-mM aqueous s o l u t i o n o f abamectin o r B - 2 3 - k e t o n e showed a t h r e e - p h a s e


2 a

response c o n s i s t i n g o f i n i t i a l l o s s o f movement w i t h i n 10 minutes w h i l e being r e s p o n s i v e t o t o u c h , p a r t i a l r e c o v e r y w i t h i n 30 minutes o f exposure and i r r e v e r s i b l e l o s s o f movement a f t e r 2 hours { 3 2 ) . I t i s not known i f the i n t e r v a l s between responses are dependent upon the c o n c e n t r a t i o n o f the c h e m i c a l i n the s o l u t i o n . The i n i t i a l l o s s o f movement i n M. i n c o g n i t a may be r e f l e c t i v e o f t h e a v e r m e c t i n s ' a c t i v i t y as GABA-agonists a t the i n h i b i t o r y synapses i n nematodes £ 4 0 ) ; t h i s p o s s i b i l i t y has been s u p p o r t e d by the o b s e r v a t i o n s , as mentioned e a r l i e r , o f Wright e t a h £32) t h a t GABA a n t a g o n i s t s p i c r o t o x i n and b i c u c u l l i n e c o u n t e r a c t e d the i n h i b i t o r y e f f e c t s o f a v e r m e c t i n s on the l o c o m o t i o n o f the j u v e n i l e s . Under s o i l f r e e c o n d i t i o n s Bp - 2 3 - k e t o n e reduced the i n v a s i o n o f cucumber r o o t s by M. i n c o g n i t a j u v e n i l e s and t h e i r f u r t h e r development a t c o n c e n t r a t i o n s much l o w e r than were needed t o i m m o b i l i z e them. I t has been proposed i n t h i s c o n t e x t t h a t a v e r m e c t i n s a f f e c t the r o o t - s e e k i n g b e h a v i o r o f j u v e n i l e s , a mode o f a c t i o n a l s o suggested f o r organophosphorus and carbamate n e m a t i c i d e s £ 4 1 ) . A v e r m e c t i n B« d i d not a f f e c t t h e p o s t - i n v a s i o n development o f M. i n c o g n i t a j u v e n i l e s i n tomato r o o t s exposed t o 1.0 ppm w/v s o l u t i o n s 48-72 hours p o s t - i n v a s i o n £ 1 6 ) . Abamectin and a v e r m e c t i n B« showed o n l y l i m i t e d downward movement: s p r a y i n g o f a e r i a l p a r t s o f tomato p l a n t s w i t h 1000 ppm w/v s o l u t i o n s r e s u l t e d i n o n l y minor i n h i b i t i o n o f r o o t g a l l i n g (Merck and C o . , I n c . , unpublished). Eggs o f M. i n c o g n i t a p l a c e d i n a 0.1 ppm w/v aqueous s o l u t i o n o f a v e r m e c t i n B - 2 3 - k e t o n e f a i l e d t o h a t c h , but when they were r i n s e d i n water 96 hours l a t e r , h a t c h i n g o c c u r r e d , which Wright e t § 2 . (41) suggest i n d i c a t e s t h a t embryogenesis proceeded normalTy~~and t h a t h a t c h i n g was h a l t e d by the i m m o b i l i z a t i o n o f t h e j u v e n i l e s by the c h e m i c a l . A v e r m e c t i n s b e g i n t o i m m o b i l i z e nematodes w i t h i n 10 minutes o f exposure £ 4 2 , 3 2 ) , w h i l e a c e t y l c h o l i n e s t e r a s e i n h i b i t o r s such as oxamyl cause h y p e r a c t i v i t y . T h i s i s p r o b a b l y the reason behind the reduced oxygen consumption by j u v e n i l e s o f t h r e e Meloidogyne spp. exposed t o 0.05 ppm s o l u t i o n s of avermectin B ^ (43). ?

1

When i n c o r p o r a t e d i n t o s o i l , a v e r m e c t i n B was s l i g h t l y more p o t e n t than abamectin and was about 10-30 times more p o t e n t than s e v e r a l organophosphate and carbamate n e m a t i c i d e s a g a i n s t M. i n c o g n i t a ( 4 4 , 4 5 ) . The l o n g e r s o i l r e s i d u a l a c t i v i t y of avermectin B , with a h a l f - l i f e i n s o i l of ?

0




2 . 5 - 3 . 0 d a y s , has been a s c r i b e d t o i t s c o n v e r s i o n by s o i l microorganisms t o a v e r m e c t i n Bp -23-ketone ( 5 ) , i t s e l f having a s o i l h a l f - l i f e o f about 30 dafs ( 4 6 ) . Interestingly, P r e i s e r e t a2« (44) determined t h a t the n e m a t i c i d a l potency o f B^ - 2 3 - k e t o n e was s l i g h t l y g r e a t e r than t h a t o f B« ; i t i s p o s s i b l e t h a t the g r e a t e r s o i l n e m a t i c i d a l potency Bp i s a c o m b i n a t i o n o f i t s own n e m a t i c i d a l a c t i v i t y combined w i t h that of i t s s o i l metabolite. S t r e t t o n e t cH. (16) have reviewed the m i c r o p l o t and l a r g e s c a l e f i e l d t r i a l s done w i t h a v e r m e c t i n B., Bp and Bp - 2 3 - k e t o n e . The s a l i e n t o b s e r v a t i o n was t h a t a t s o i l a p p l i c a t i o n r a t e s r a n g i n g from 0.168 t o 1.52 kg a i / h e c t a r e a l l t h e a v e r m e c t i n s were e f f e c t i v e i n c o n t r o l l i n g the r o o t k n o t nematodes. However, the d i f f e r e n c e s i n e f f i c a c y among the avermectins observed i n the c o n t r o l l e d greenhouse experiments do not o b t a i n i n the l a r g e s c a l e f i e l d t r i a l s , a t l e a s t among t h e l i m i t e d number done so f a r . In t h i s c o n t e x t , the i n f l u e n c e o f the p h y s i c o - c h e m i c a l p r o p e r t i e s on the b e h a v i o r o f the avermectins i n s o i l should be c o n s i d e r e d . The water s o l u b i l i t y o f abamectin i s 7.8 ppb w/v and i t s l e a c h i n g p o t e n t i a l through many types o f s o i l i s e x t r e m e l y low £ 4 7 , 4 8 ) , w i t h the r e s u l t t h a t the chemical does not move i n t o the r F i z o s p h e r e r e a d i l y u n l e s s m e c h a n i c a l l y i n c o r p o r a t e d t o a s u f f i c i e n t d e p t h . These f a c t o r s have l i m i t e d t h e s u c c e s s f u l use o f the a v e r m e c t i n s as s o i l n e m a t i c i d e s . P a r a d o x i c a l l y however, the p h y s i c o - c h e m i c a l p r o p e r t i e s a l s o c o n f e r many p o t e n t i a l advantages upon the use o f the a v e r m e c t i n s as n e m a t i c i d e s . T h e i r r a p i d d e g r a d a t i o n and poor m o b i l i t y suggest t h a t f i e l d a p p l i c a t i o n s would not r e s u l t i n p e r s i s t e n t r e s i d u e s o r c o n t a m i n a t i o n o f ground water ( 4 8 ) . Photodegradation E x t e n s i v e and r a p i d p h o t o d e g r a d a t i o n a f t e r a p p l i c a t i o n t o p l a n t s u r f a c e s appears t o be a prominent c h a r a c t e r i s t i c o f abamectin. S t u d i e s on the f a t e o f t r i t i a t e d abamectin a f t e r a p p l i c a t i o n t o c o t t o n l e a v e s showed t h a t the compound was r a p i d l y degraded on l e a f s u r f a c e s ; a t 48 hours p o s t - t r e a t m e n t , o n l y 18.4% o f the r e c o v e r e d r a d i o a c t i v e m a t e r i a l was abamectin £ 4 8 ) . J e n k i n s e t a2. £49) a p p l i e d abamectin t o greenhouse-grown chrysanthemums a t 22.4 and 44.8 g a i / h e c t a r e and determined t h a t d i s l o d g e a b l e abamectin r e s i d u e s on the l e a f s u r f a c e s were reduced by 90-98% by 24-72 hours p o s t a p p l i c a t i o n ( F i g u r e 2 ) . W h i l e the dynamics o f the d e g r a d a t i o n would vary depending upon the morphology o f the l e a f s u r f a c e and the i n t e n s i t y o f the l i g h t , i t i s c l e a r t h a t t h e s u r f a c e d e p o s i t s o f abamectin are degraded r a p i d l y .


BABU



The r a p i d d i s a p p e a r a n c e o f the s u r f a c e d e p o s i t s o f abamectin i s an advantage i n terms o f n o n t a r g e t , b e n e f i c i a l o r g a n i s m s . An example o f t h i s can be seen i n the case o f f o r a g i n g honeybees ( F i g u r e 3 ) . Field-grown a l f a l f a f o l i a g e t r e a t e d w i t h abamectin a t d i f f e r e n t r a t e s was c o l l e c t e d a t v a r i o u s p o s t - t r e a t m e n t i n t e r v a l s . Bees were then kept i n c o n t i n u o u s c o n t a c t w i t h t h i s f o l i a g e f o r 24 hours a t which time t h e i r m o r t a l i t y was a s s e s s e d . There was a steady d e c l i n e i n m o r t a l i t y , r e s u l t i n g i n v i r t u a l l y no m o r t a l i t y a t 36 hours p o s t - t r e a t m e n t ( 5 0 ) . Trans!aminar In s p i t e deposits, activity as being

Activity

o f the observed r a p i d d e g r a d a t i o n o f the s u r f a c e abamectin shows h i g h p o s t - a p p l i c a t i o n r e s i d u a l on l e a v e s . T h i s anomaly can be e x p l a i n e d due t o the t r a n s l a m i n a r a c t i v i t y o f abamectin.

T r a n s l a m i n a r a c t i v i t y o f chemical r e f e r s t o the movement o f chemical from the t r e a t e d s u r f a c e i n t o t h e l e a f so t h a t i n s e c t o r m i t e p e s t s f e e d i n g on the u n t r e a t e d s u r f a c e would be a f f e c t e d £ 5 1 , 52). In the c o n t e x t o f a b a m e c t i n , i t can be proposed t h a t w h i l e the s u r f a c e d e p o s i t s are q u i c k l y d e p l e t e d (48, 5 3 ) , the amount which has p e n e t r a t e d i n t o the l e a f forms a w i t h i n - t h e - l e a f r e s e r v o i r , which g i v e abamectin i t s residual m i t i c i a l a c t i v i t y £6). Wright e t a h £54) have demonstrated such t r a n s l a m i n a r a c t i v i t y i n bean, c o t t o n and chrysanthemum l e a v e s . In t h e i r e x p e r i m e n t s , abamectin was a p p l i e d t o the upper o r lower s u r f a c e o f the l e a f and m i t e s were c o n f i n e d on the o p p o s i t e s u r f a c e . The d i f f e r e n c e s i n the a c t i v i t y o f abamectin among t h e t h r e e p l a n t s are p o s s i b l y due t o s t r u c t u r a l d i f f e r e n c e s i n the c u t i c u l a r waxes; Wright e t a2. (54) do p o i n t out t h a t bean l e a v e s have the l e a s t and chrysanthemum the most waxy c u t i c l e . There were no s i g n i f i c a n t d i f f e r e n c e s i n t r a n s l a m i n a r movement whether the chemical was a p p l i e d t o the upper and lower s u r f a c e . T h i s o b s e r v a t i o n i s o f p a r t i c u l a r i n t e r e s t because p e n e t r a t i o n o f c h e m i c a l s i n t o l e a v e s i s u s u a l l y assumed t o be g r e a t e r through the lower than the upper l e a f s u r f a c e £ 5 5 , 5 6 ) . L i t t l e i s known about a b a m e c t i n ' s p a t t e r n s o f movement w i t h i n the l e a f a f t e r i t has p e n e t r a t e d the c u t i c l e o r whether i t s presence i n the l e a f mesophyll i s a p o p l a s t i c o r s y m p l a s t i c o r b o t h . However, p l a n t p a r a s i t i c m i t e s are d e s t r u c t i v e f e e d e r s and withdraw the c o n t e n t s o f the p a l i s a d e c e l l s and those o f the mesophyll £ 5 7 , 58) and thus seem t o i n g e s t s u f f i c i e n t amounts o f abamectin a s s o c i a t e d e i t h e r w i t h t h e cytoplasm o r the c e l l w a l l s . The depth o f p e n e t r a t i o n need not extend from the t r e a t e d upper e p i d e r m i s t o the u n t r e a t e d lower e p i d e r m i s ( o r v i c e v e r s a ) where m i t e s f e e d : i t i s known t h a t the s t y l e t s o f the t e t r a n y c h i d m i t e


100



FOLIAR RESIDUES (ng/cm sq.) 8 T

0

8

16

24

32

40

48

56

64

72

TIME HOURS (POST-TREATMENT)

F i g u r e 2: F o l i a r d i s l o d g e a b l e r e s i d u e s (expressed as nanograms/cm ) o f abamectin a p p l i e d a t two d i f f e r e n t r a t e s t o chrysanthemum l e a v e s , determined a t d i f f e r e n t times a f t e r a p p l i c a t i o n . ( A d a p t e d from r e f . 4 9 ) . 100-

AQE (HRS) OF RESIDUE

F i g u r e 3: E f f e c t s on honeybees ( A p i s m e l l i f e r a ) o f r e s i d u e s o f abamectin a p p l i e d a t two r a t e s onto a l f a l f a f o l i a g e . Bees were i n t r o d u c e d onto t r e a t e d f o l i a g e b e a r i n g r e s i d u e s aged f o r d i f f e r e n t time p e r i o d s (Adapted from r e f . 5 0 ) .


BABU


Tetranychus u r t i c a e can p e n e t r a t e the l e a f t o a depth of 70-100 urn on a bean l e a f o f a p p r o x i m a t e l y 180 urn t h i c k n e s s 158).

Behavior i n S o i l Gullo et £46) d i s c o v e r e d t h a t a v e r m e c t i n B incubated i n a sandy loam s o i l under greenhouse c o n d i t i o n s was r a p i d l y degraded, w i t h a h a l f - l i f e o f 2.5 t o 3.0 d a y s , t o a m e t a b o l i t e i d e n t i f i e d as a 23-keto d e r i v a t i v e formed by s o i l . T h i s m e t a b o l i t e was formed by s o i l m i c r o o r g a n i s m s : i n s t e r i l i z e d m o i s t s o i l a f t e r 13 days, l e s s than 1% o f the added Bp was c o n v e r t e d t o the m e t a b o l i t e compared w i t h 44% under n o n - s t e r i l e c o n d i t i o n s . At l e a s t t h r e e microorganisms c a p a b l e o f such t r a n s f o r m a t i o n have been r e p o r t e d ( 4 6 ) .


?

S i m i l a r s t u d i e s on the f a t e o f t r i t i u m - l a b e l e d a v e r m e c t i n Bi n t h r e e k i n d s o f s o i l have shown t h a t under a e r o b i c c o n d i t i o n s i t was degraded a t a r a p i d r a t e , w i t h a h a l f - l i f e i n sandy loam o f 14-28 d a y s , i n c l a y 25-56 days, and i n c o a r s e sand 56 days. The major s o i l d e g r a d a t i o n p r o d u c t was an e q u i l i b r i u m m i x t u r e w i t h a r a t i o o f 1:2.5 o f the 8 - a l p h a - h y d r o x y d e r i v a t i v e and the c o r r e s p o n d i n g o p e n - r i n g aldehyde d e r i v a t i v e £ 4 8 ) . No f u r t h e r work r e g a r d i n g the n e m a t i c i d a l a c t i v i t y o f t h e s e m e t a b o l i t e s has been r e p o r t e d . L e t h a l And S u b l e t h a l A c t i v i t i e s A v e r m e c t i n s d i f f e r f u n d a m e n t a l l y from o t h e r n e u r o a c t i v e p e s t i c i d e s , p r o b a b l y i n keeping w i t h t h e i r GABAergic mode o f a c t i o n , i n t h a t they do not cause h y p e r a c t i v i t y i n the a f f e c t e d organisms. I m m o b i l i z a t i o n o f nematodes soon a f t e r exposure t o a v e r m e c t i n s as r e p o r t e d by Wright e t a h £32) was a l s o r e p o r t e d e a r l i e r £5) i n the case o f m i t e s and i n s e c t s . The e f f e c t s o f such a mode o f a c t i o n , depending upon the degree o f exposure t o the c h e m i c a l , can be l e t h a l o r sublethal. As Strong and Brown £7) o b s e r v e , t h e r e i s no s a t i s f a c t o r y d e f i n i t i o n o f a " l e t h a l e f f e c t " ; however, death i n the sense o f an i r r e v e r s i b l e e f f e c t , d e s c r i b e d , f o r example, by Deecher e t a h £59) as f a i l u r e t o respond to t a c t i l e s t i m u l u s , o c c u r s i n 72-120 hours a f t e r s u f f i c i e n t exposure t o abamectin. The c o m p a r a t i v e symptoms o f t o x i c i t y o f abamectin and the p y r e t h r o i d c y p e r m e t h r i n when a p p l i e d t o p i c a l l y t o t h e l e p i d o p t e r a n i n s e c t c o t t o n bollworm ( H e l i o t h i s zea) l a r v a e are i l l u s t r a t i v e (B. I. G o l l , p e r s o n a l communication]". In the case o f a b a m e c t i n , t h e r e was f l a c c i d p a r a l y s i s , cessation of feeding, arrested ecdysis manifested as the presence o f head c a p s u l e a t the t i p o f the mandibles and a s i l v e r y grey c o l o r o f an o t h e r w i s e u n a f f e c t e d body w i t h t h e presence o f h e a r t b e a t o b s e r v a b l e i n the t h i r d p o s t e r i o r


102



abdominal segment. The presence o f h e a r t b e a t has a l s o been observed i n H. zea a d u l t s which have i n g e s t e d abamectin ( 6 0 ) . C y p e r m e t h r i n , i n c o n t r a s t , r e s u l t e d i n r a p i d c o n v u l s i o n s and a shrunken l a r v a l body accompanied by an i n t e n s e d a r k e n i n g of the c u t i c l e . A p a r t from the d i r e c t t o x i c e f f e c t s r e s u l t i n g i n m o r t a l i t y , an i n s e c t i c i d e o r a m i t i c i d e can have o t h e r n o n l e t h a l , y e t d e l e t e r i o u s e f f e c t s on the organism. Moriarty (61) d e s c r i b e d many such e f f e c t s induced by a number o f e a r l i e r i n s e c t i c i d e s . Kumar and Chapman £62) r e c e n t l y r e p o r t e d on such s u b l e t h a l e f f e c t s such as the i n h i b i t i o n o f f e e d i n g , developmental d i s t u r b a n c e s and r e d u c t i o n i n f e c u n d i t y i n the diamondback moth P l u t e l l a x y l o s t e l l a . Knowles £63) has d e s c r i b e d the e f f e c t s , o t h e r than l e t h a l i t y , o f some formamidines on p l a n t p a r a s i t i c m i t e s . Among such s u b l e t h a l e f f e c t s o f the a v e r m e c t i n s , reduced f e c u n d i t y has a t t r a c t e d p a r t i c u l a r a t t e n t i o n . L o f g r e n and W i l l i a m s £64) observed t h a t a b a m e c t i n , when f e d t o the c o l o n i e s , i n h i b i t e d the r e p r o d u c t i v e c a p a c i t y o f the queens o f t h e red imported f i r e ant S. i n v i c t a , w i t h the r e s u l t a n t t r u n c a t i o n o f the c o l o n i e s . S u b s e q u e n t l y , Glancey e t a h (65) h i s t o l o g i c a l l y examined the o v a r i e s o f queens from c o l o n i e s t r e a t e d 22-weeks e a r l i e r and d e s c r i b e d the damage as: h y p e r t r o p h y o f the squamous e p i t h e l i u m which sheathes the o v a r i o l e s and p y c n o s i s o f the nurse c e l l n u c l e i which r e s u l t e d i n complete absence o r r e d u c t i o n i n the numbers and s i z e o f eggs produced. There have a l s o been r e p o r t s o f reduced f e c u n d i t y among s u r v i v o r s o f l e p i d o p t e r a n i n s e c t s exposed t o a b a m e c t i n . A d u l t s o f the c o d l i n g moth C y d i a pomonella d e v e l o p i n g from l a r v a e exposed t o abamectin produced s i g n i f i c a n t l y fewer eggs £ 6 6 ) . Beach and Todd £67) f e d abamectin t o male and female a d u l t s o f soybean l o o p e r P s e u d o p l u s i a i n c l u d e n s and subsequent matings o f such i n s e c t s r e s u l t e d i n reduced f e c u n d i t y and f e r t i l i t y . A v a r i a t i o n has been t h a t o f Robertson e t £68) where f e r t i l i t y but not f e c u n d i t y was a f f e c t e d i n matings o f males and females o f the western spruce budworm C h o r i s t o n e u r a o c c i d e n t a l i s developed from l a r v a e exposed t o a b a m e c t i n . S u b l e t h a l e f f e c t s have been r e p o r t e d t o i n c l u d e p o s t - e m b r y o n i c development o f some i n s e c t s ; H e l i o t h i s v i r e s c e n s and H. zea l a r v a e which s u r v i v e d abamectin t r e a t m e n t c o n t i n u e d m o l t i n g but d i d not s u r v i v e p u p a t i o n £ 6 9 ) . The consequence was t h a t even at doses below LD few a d u l t s emerged from the pupae. S u b l e t h a l doses r e s u l t e d i n p r e v e n t i o n o f p u p a t i o n i n the e a s t e r n y e l l o w j a c k e t Vespula m a c u l i f r o n s (70) and e x t e n s i o n o f the pupal p e r i o d i n c o d l i n g moth C. pomonella l a r v a e ( 6 6 ) . An i n s e c t i c i d e ' s e f f e c t on r e p r o d u c t i v e p o t e n t i a l can be caused by a lowered i n c i d e n c e o f m a t i n g , a s h o r t e n e d l i f e



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s p a n , the s u p p r e s s i o n o f the r e p r o d u c t i v e organs and a d i r e c t t o x i c e f f e c t on the eggs (62). There i s no e v i d e n c e t h a t abamectin a f f e c t s i n s e c t o r m i t e r e p r o d u c t i v e t i s s u e s directly. Even the o v a r i a n r e g r e s s i o n i n S. i n v i c t a observed by Glancey e t a h £ 6 5 ) s h o u l d be c o n s i d e r e d from the p e r s p e c t i v e t h a t a t the time o f t h e i r o b s e r v a t i o n s 22 weeks had e l a p s e d s i n c e t r e a t m e n t . The observed e f f e c t s c o u l d have been due t o s t a r v a t i o n o f the queen and the r e s u l t a n t d y s f u n c t i o n a l changes i n the g e n e r a l m e t a b o l i s m . The i n t r o d u c t i o n o f c o n t r o l s c o n s i s t i n g o f u n t r e a t e d but s t a r v e d queens and h i s t o l o g i c a l o b s e r v a t i o n s a t s h o r t e r p o s t - t r e a t m e n t i n t e r v a l s would c l a r i f y t h i s r e p o r t . In the absence o f d i r e c t o b s e r v a t i o n s on oogenesis o r embryogenesis, the reduced e f f e c t s o f abamectin on f e c u n d i t y w i l l have t o f o l l o w the obverse o f the h o r m o l i g o s i s h y p o t h e s i s proposed by Luckey £ 7 1 ) i n t h a t s u b l e t h a l p o i s o n i n g i s l i k e l y t o reduce t h e general f i t n e s s o f the i n s e c t s o r m i t e s and t h e r e b y t h e i r r e p r o d u c t i v e c a p a c i t y and even the p o s t - e m b r y o n i c development. A r e s u l t o f i m m o b i l i z a t i o n i s the c e s s a t i o n o f f e e d i n g , which has been termed as f e e d i n g i n h i b i t i o n . Strong and Brown £ 7 ) o b j e c t t o such a d e s c r i p t i o n on the r e a s o n i n g t h a t a n t i f e e d a n t p r o p e r t i e s s h o u l d not be a s c r i b e d t o a chemical u n l e s s such p r o p e r t i e s can be s e p a r a t e d from general t o x i c i t y and d e b i l i t a t i o n . In my e x p e r i e n c e , i n a l l i n s t a n c e s where i m m o b i l i z a t i o n o r c e s s a t i o n o f f e e d i n g have been o b s e r v e d , death e v e n t u a l l y r e s u l t e d . I t appears t h a t an observed s u b l e t h a l e f f e c t i s r e a l l y the b e g i n n i n g o f the l e t h a l e f f e c t . The r e l a t i o n s h i p s between the c o n c e n t r a t i o n o f the c h e m i c a l , speed o f a c t i v i t y on d i f f e r e n t i n s e c t s and the consequences o f d e b i l i t a t e d f e e d i n g , f o r example, the r e d u c t i o n i n the l e a f area consumed, are y e t t o be s t u d i e d . Differential

Toxicities

Among the i n s e c t s which were r e c o r d e d as being a f f e c t e d by abamectin were t h r e e l e p i d o p t e r a n i n s e c t s a g a i n s t which abamectin showed d i f f e r e n t i a l t o x i c i t y £ 5 ) . The f o l i a r i n g e s t i o n t o x i c i t y L C g v a l u e s ( f o r neonate l a r v a e ) were 0.02 ppm f o r the tomato hornworm Manduca s e x t a , 0.75-1.2 ppm f o r the cabbage l o o p e r T r i c h o p l u s i a n i and 1.5 ppm f o r the s o u t h e r n armyworm S. e r i d a n i a . F u r t h e r r e s e a r c h on the t o x i c i t y o f abamectin t o l e p i d o p t e r a n i n s e c t s has shown some i n t e r e s t i n g c h a r a c t e r i s t i c s of abamectin. 0

Anderson e t a h (72) c o n f i r m e d the o b s e r v a t i o n by P u t t e r e t cH. £ 5 ) t h a t S. e r i d a n i a was l e s s s e n s i t i v e t o abamectin tTTan H. v i r e s c e n s , both i n t r e a t e d f o l i a g e i n g e s t i o n by neonate and t o p i c a l a p p l i c a t i o n s t o t h i r d i n s t a r l a r v a e among t h e H e l i o t h i s spp. H. v i r e s c e n s i s more s u s c e p t i b l e t o abamectin than H. zea (73, 74). B u l l £ 6 9 ) c o n f i r m s the


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d i f f e r e n c e s i n the s e n s i t i v i t i e s . o f H. v i r e s c e n s and H. zea and a l s o demonstrates the marked i n s e n s i t i v i t y o f the f a T T armyworm S. f r u g i p e r d a . The reasons f o r the d i f f e r e n c e s i n the t o x i c i t y o f abamectin t o t h e d i f f e r e n t l e p i d o p t e r a n i n s e c t s are not clear. B u l l £ 6 9 ) , by u s i n g o r a l l y a d m i n i s t e r e d t r i t i a t e d B, , observed t h a t p h y s i o l o g i c a l p r o c e s s e s l i k e a b s o r p t i o n ffom the l a r v a l m i d g u t , metabolism and e x c r e t i o n o f the m e t a b o l i t e s were slower i n H. v i r e s c e n s than i n H. zea o r S. f r u g i p e r d a . S i m i l a r l y , s i g n i f i c a n t l y more t r i t i a t e d a v e r m e c t i n B, was r e c o v e r e d from the heads o f H. v i r e s c e n s . N e i t h e r s l o w e r metabolism nor f a s t e r a c c u m u l a t i o n i n the head can c a t e g o r i c a l l y e x p l a i n the g r e a t e r s e n s i t i v i t y o f H. v i r e s c e n s , c o n s i d e r i n g t h a t t h e r e were no s i g n i f i c a n t d i f f e r e n c e s between H. zea and S. f r u g i p e r d a i n t h e metabolism o f a v e r m e c t i n B- . There were s u b s t a n t i a l d i f f e r e n c e s between them i n t h e i r s u s c e p t i b i l i t y t o a v e r m e c t i n B, . T h i s a s p e c t can be b e t t e r understood by t e s t i n g the h y p o t h e s i s t h a t d i f f e r e n t i a l s e n s i t i v i t y i s r e l a t e d t o d i f f e r e n c e s i n the a f f i n i t y t o , and t h e r e f o r e the a c c u m u l a t i o n o f , abamectin a t the GABA-receptors i n the i n s e c t s (69). Conclusion In summarizing the b i o l o g i c a l - p e s t i c i d a l a c t i v i t i e s o f the a v e r m e c t i n s , two p a r a d o x i c a l p r o p e r t i e s can be n o t e d . First, f o l i a r s u r f a c e d e p o s i t s are r a p i d l y degraded w i t h the r e s u l t t h a t many b e n e f i c i a l organisms do not encounter the t o x i c e n t i t y s i g n i f i c a n t l y . However, a v e r m e c t i n s seem t o p e n e t r a t e t h e l e a f l a m e l l a e and be a v a i l a b l e as a p e s t i c i d a l r e s e r v o i r a g a i n s t m i t e s and i n s e c t s . Second, w h i l e they a r e p o t e n t a g a i n s t s o i l nematodes, t h e y are a l s o n e a r l y i n s o l u b l e i n water and have an e x t r e m e l y low l e a c h i n g p o t e n t i a l . A c l e a r e r u n d e r s t a n d i n g o f t h e mechanisms behind the l e a f c u t i c u l a r p e n e t r a t i o n would be h e l p f u l i n f i n d i n g ways t o i n c r e a s e the t o x i c r e s e r v o i r w i t h i n the l e a f w h i l e the s u r f a c e d e p o s i t s remain l o w , w i t h the a t t e n d a n t advantages. S i m i l a r l y , d e f i n i n g the mechanisms o f s o i l b i n d i n g would be h e l p f u l i n f i n d i n g ways t o i n c r e a s e the a v e r m e c t i n s ' m o b i l i t y and presence i n s o i l w a t e r t o a c t a g a i n s t nematodes. The s u b l e t h a l a c t i v i t i e s o f the a v e r m e c t i n s a l s o need further scrutiny. For example, i s the r e d u c t i o n i n f e c u n d i t y a d i r e c t e f f e c t o r an i n d i r e c t one due t o the e f f e c t o f the a v e r m e c t i n s on the ' f i t n e s s ' o f the organism? The consequences o f reduced f e c u n d i t y and d e b i l i t a t e d f e e d i n g need t o be q u a n t i f i e d i n terms o f the e f f e c t s on the pest p o p u l a t i o n dynamics. More r e s e a r c h a l o n g the l i n e s t h a t B u l l (69) suggests can e x p l a i n the mechanisms behind the l e s s e r s u s c e p t i b i l i t y o f some e c o n o m i c a l l y i m p o r t a n t l e p i d o p t e r a n insects.


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The avermectins mark an important event in the search for natural products of microbial origin which are useful in agriculture. However, they may be only the beginning. Given their broad range of pesticidal activities, it is possible that future screening programs or semisynthetic modifications will yield entities which have one or more characteristics such as exclusive miticidal or insecticidal activity, enhanced cuticular penetration, resistance to photodegradation and greater soil mobility. Acknowledgments Many thanks to Connie M. Graf for her help in preparing this paper and to John G. MacConnell for his critical comments. Literature Cited 1.

Campbell, W. C.; Burg, R. W.; Fisher, M. H.; Dybas, R. A. In Pesticide Synthesis Through Rational Approaches, Magee, P. S.; Kohn, G. K.; Menn, J. J.; Eds.; ACS Symposium Series No. 255; American Chemical Society, Washington, D.C., 1984, pp. 5-20. 2. Stapley, E. O.; Woodruff, H. B. In Proceedings, An International Conference on Trends in Antibiotic Research, Umezawa, H.; Demain, A. L.; Hata, J.; Hutchinson, C. R., Eds.; Japan Antibiotics Research Association, Tokyo, 1982, pp. 154-70. 3. Woodruff, H. B.; Burg, R. W. In Discoveries in Pharmacology, Volume 3: Pharmacological Methods, Receptors & Chemotherapy; Parnham, M. J.; Bruinvels, J., Eds.; Elsevier Science Publishers, 1986, pp. 303-51. 4. Burg, R. W.; Miller, B. M.; Baker, E. E.; Birnbaum, J.; Currie, S. A.; Hartman, R.; Kong, Y. L.; Monaghan, R. L.; Olson, G.; Putter, I.; Tunac, J. B.; Wallick, H.; Stapley, E. O.; Oiwa, R.; Omura, S. Antimicrob. Agents Chemother. 1979, 15, 361-67. 5. Putter, I.; MacConnell, J. G.; Preiser, F. A.; Haidri, A. A.; Ristich, S. S.; Dybas, R.A. Experientia 1981, 37, 963-64. 6. Dybas, R. A.; Green, A. St. J. In: 1984 British Crop Protection Conference. Pests and Diseases. British Crop Protection Council, Croydon, U.K., Volume 3, pp. 947-54. 7. Strong, L.; Brown, T. A. Bull ent. Res. 1987, 77, 357-89. 8. Albers-Schonberg, G.; Arison, B. H . , ; Chabala, J. C.; Douglas, A. W.; Eskola, R.; Fisher, M. H.; Lusi, A.; Mrozik, H.; Smith, J. L.; Tolman, R. L. J. Am. Chem. Soc. 1981, 103, 4216-21. 9. Springer, J. P.; Arison, B. H.; Hirschfield, J. M.; Hoogsteen, K. J. Am. Chem. Soc. 1981, 103, 4221. 10. Fisher, M. H.; Mrozik, H. In Macrolide Antibiotics, Academic Press, New York, 1984, pp. 553-606.


106



11.

Aoki, Α.; Fukuda, R.; Nakayabu, T.; Ishibashi, K.; Takeichi, C.; Ishida, M. J. Antibiotics. 1976, 29, 76-14, 76-35. 12. Mishima, H. In IUPAC Pesticide Chemistry 2, Miyamoto, J.; Kearney, P. C.; Eds.; Pergamon Press, Oxford, 1983; pp. 129-34. 13. Mishima, H.; Kurabayashi, M.; Tamura, C.; Sato, S.; Kuwano, H.; Saito, A. Tetrahedron Lett. 1975, p. 711. 14. Campbell, W. C.; Fisher, M. H.; Stapley, E. O.; Albers-Schonberg, G.; Jacob, Τ. Α., Science 1983, 221, 823-28. 15. Campbell, W. C.; Benz, G. W. J. Vet. Pharmacol. Therap., 1984, 7, 1-16. 16. Stretton, A. O. W.; Campbell, W. C.; Babu, J. R. In Vistas on Nematology; Veech, J. Α.; Dickson, D. W., Eds.; Society of Nematologists, Inc., Hyattsville, Maryland, 1987; pp. 136-46. 17. Aziz, M. A. Rev. Infect. Pis. 1986, 8, 500-04. 18. Anonymous WHO Chronicle 1985, 39, Supplement. 19. USAN Council. Clin. Pharm. Ther. 1988, 43, 91-92. 20. Wright, D. J., In Neuropharmacology and Pesticide Action, Ford, M. G.; Lunt, G. G.; Deay, R. D.; Usherwood, P. N. R., Eds.; Ellis Horwood, Chichester, 1986, pp. 174-202. 21. Calcott, P. H.; Fatig, III, R. O. J. Antibiot. 1984, 37, 253-59. 22. Onishi, J. C.; Miller, T. W. J. Antibiot. 1985, 38, 1568-72. 23. Umezawa, H., In Index of Antibiotics from Actinomycetes, University Park Press, Tokyo, 1967; p. 476. 24. Gordnier, P. M.; Brezner, J.; Tanenbaum, S. W. J. Antibiot. 1987, 40, 110-12. 25. Wang, C. C. Proceedings of Satell. Symp. 1984. Plenum, New York, 1986, pp. 125-38. 26. Kass, I.S.; Wang, C. C.; Walrond, J. P.; Stretton, A. O. W. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 6211-15. 27. Fritz, L. C.; Wang, C. C.; Gorio, A. Proc. Natl. Acad. Sci. U.S.A. 1979, 76, 2062-66. 28. Pong, S. S.; Wang, C. C. Neuropharmac. 1980, 19, 311-17. 29. Pong, S. S.; Wang, C. C. In Membranes and Genetic Disease. Sheppard, J. R.; Anderson, V. E.; Eaton, J. W., Eds.; Liss, New York, 1982; pp. 373-95. 30. Pong, S. S.; DeHaven, R.; Wang, C. C. Biochimica et Biophysica Acta. 1981, 646, 143-50. 31. Tallman, J. F.; Thomas, J. W.; Gallager, D. W. Nature 1978, 274, 383-85. 32. Wright, D. J.; Birtle, A. J.; Roberts, I. T.J. Parasitology 1984, 88, 375-82. 33. Takeuchi, A.; Takeuchi, N. J. Physiology 1969, 205, 377-91. 34. Olsen, R. W.: Snowman, A. M. J. Neurochemistry 1985, 44, 1074-82.



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35. Trifiletti, R. R.; Snowman, A. M.; Snyder, S. H. European J. of Pharmacol. 1985, 106, 441-47. 36. Olsen, R. W.; Wong, E. H. F.; Starrer, G. B.; King, R. G. Federation Proceedings 1984, 43, 2773-78. 37. Duce, I. R.; Scott, R. H. British J. Pharmacol. 1985, 85, 395-401. 38. Gregory, E.; Foreyt, W. J.; Breeze, R. Veterinary Medicine February, 1985, pp. 114-17. 39. Martin, R. J. Biochem. Soc. Trans. 1987, 15, 61-5. 40. Mellin, T. N.; Busch, R. D.; Wang, C. C. Neuropharmacology 1983, 22, 89-96. 41. Wright, D. J.; Birtle, A. J.; Corps, A. E.; Dybas, R. A. Ann. appl. Biol. 1984, 103, 465-70. 42. Sano, M.; Terada, M.; Ishi, A. I.; Kino, H. Experientia 1981, 37, 844-47. 43. Nordmeyer, D.; Dickson, D. W. J. Nematology 1981, 13, 452-53. 44. Preiser, F. A.; Babu, J. R.; Dybas, R. A.; Haidri, A. A.; Putter, I. J. Nematology 1981, 13, 457 (Abstr.). 45. Sasser, J. N.; Kirkpatrick, T. L.; Dybas. R. A. Plant Disease 1982, 66, 691-93. 46. Gullo, V. P.; Kemf, A. J.; MacConnell, J. G.; Mrozik, H. ; Arison, B.; Putter, I. Pesticide Science 1983, 14, 153-57. 47. Bull, D. L. Southwestern Entomologist Supplement No. 7, 1985, pp. 2-10. 48. Bull, D. L.; Ivie, G. W.; MacConnell, J. G.; Gruber, V. F.; Ku, C. C.; Arison, B. H.; Stevenson, J. M.; Vandenheuvel, W. A. J. J. Agric. Fd. Chemistry 1984, 32, 94-102. 49. Jenkins, J. J.; Rosenthal, H. S.; Mollet, J.; Brown, R. D.; Norton, J.; Dybas, R. A. In American Chemical Society-Agrochemicals, Proceedings, 193rd ACS. National Meeting, April 1987, Denver, Colorado. 50. Atkins, E. L., In Annual Report, Dept. of Entomology, University of California, Riverside, 1980, p. 693. 51. Cooke, V. A. Annals of appl. Biol. 1963, 51, 485-88. 52. Harrison, I. R.; Kozlik, H.; McCarthy, J. F.; Palmer, B. F.; Weighton, D. M. Meded. Rijksfac. Landbouwwet. Gent. 1972, 37, 765-75. 53. Iwata, Y.; MacConnell, J.; Flor, J. E.; Putter, I.; Dinoff, T. M. J. Agric. Fd. Chem. 1984, 33, 467-71. 54. Wright, D. J.; Loy, A.; Green, A. St. J.; Dybas, R. A. Med. Fac. Landbouww, Rijksuniv. Gent. 1985, 50/2b, 595-601. 55. Hull, H. M., In Residue Reviews, Gunther, F. A.; Gunther, J. D. Eds.; Springer-Verlag, New York, 1970, pp. 1-155. 56. Sargent, J. A., Ann. Rev. Plant Physiol. 1965, 11, 1-12. 57. Baker, J. E.; Connell, W. A. Annals of the Entomological Society of America 1963, 56, 733-36. 58. Mothes, U.; Seitz K. Acarologia 1982, 23, 149-57.


108

BIOLOGICALLY ACTIVE NATURAL PRODUCTS 59. 60. 61. 62.


63.

64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74.

Deecher, D. C.; Brezner, J.; Tanenbaum, S. W. J. econ. Entomol. 1987, 80, 1284-87. Agee, H. R. Agric. Entomology 1985, 2, 325-36. Moriarty, F. Biological Reviews 1969, 44, 321-57. Kumar, K.; Chapman, R. B. Pesticide Science 1984, 15, 344-52. Knowles, C. A. In Sites of Action for Neurotoxic Pesticides, Hollingworth, R. M.; Green, M. B., Eds.; ACS Symposium Series No. 356; American Chemical Society, Washington, D.C., 1987; pp. 174-90. Lofgren, C. C.; Williams, D. F. J. econ. Entomol. 1982, 75, 798-803. Glancey, B. M.; Lofgren, C. S.; Williams, D. F. J. Med. Entomol. 1982, 19, 743-47. Reed, D. K.; Tromley, N. J.; Reed, G. L. J. econ. Entomol. 1985, 78, 1067-71. Beach, R. M.; Todd, J. W. J. econ. Entomol. 1985, 78, 1125-28. Robertson, J. L.; Richmond, C. E.; Preisler, H. K. J. econ. Entomol. 1985, 78, 1129-32. Bull, D. L. J. Agric. Fd. Chem. 34, 74-78. Parrish, M. D.; Roberts, R. B. J." econ. Entomol. 1984, 77, 769-72. Luckey, T. D. J. econ. Entomol. 1968, 61, 7-12. Anderson, T. E.; Babu, J. R.; Dybas, R. A.; Metha, T. J. econ. Entomol. 1986, 79, 197-201. Wright, J. E.; Jenkins, J. N.; Villavaso, E. J. Southwestern Entomologist Supplement No. 7, 1985, pp. Wolfenbarger, D. A.; Johnson, A. W.; Herzog, G. A.; Tappan, W. B. Southwestern Entomologist Supplement No. 7, 1985, pp. 17-26.

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