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1
C H I A C. KU
and I N D E R P. K A P O O R
American Cyanamid Company, Agricultural Research Division, Princeton, NJ 08540
*
(I) (Cyolane phosfolan, a r e g i s t e r e d trademark of the American Cyanamid Company) and (II) (Cytrolane mephosfolan, a r e g i s t e r e d trademark of the American Cyanamid Company) are systemic οrganophosphate i n s e c t i c i d e s c o n t a i n i n g the 1,3 d i t h i o lane r i n g . Phosfolan is u s e f u l f o r the c o n t r o l of s e v e r a l c o t t o n , cabbage and tobacco i n s e c t s . I t is e f f e c t i v e against many species of Spodoptera, such as the Egyptian c o t t o n leafworm,S, littoralis, I t i s a l s o e f f e c t i v e against leafhoppers, aphids, t h r i p s , mites, w h i t e f l i e s , lygus bugs, l e a f miners, cutworms, flea b e e t l e s , and alfalfa w e e v i l s , while mephosfolan i s being used f o r the c o n t r o l of many lepidopterous and other pests of c o t t o n , c o r n , r i c e , sorghum, sugarcane, e t c . , i n s e v e r a l c o u n t r i e s , e s p e c i a l l y i n the Middle East and A s i a . Among the prominent r i c e pests c o n t r o l l e d are r i c e h i s p a (Hispa armigera), r i c e g a l l midge ( P a c h y d i p l o s i s oryzae), and all major r i c e stem borers l i k e C h i l o s u p p r e s s a l i s and Tryporyza i n c e r t u l a s . The i n v e s t i g a t i o n of the metabolic f a t e s of the two C-dithiolane i n s e c t i c i d e s l a b e l e d in the imino carbon p o s i t i o n was i n i t i a t e d to study the e x c r e t i o n , t i s s u e residue behavior and the nature of the major metabolites i n r a t s . A d d i t i o n a l s t u d i e s were undertaken to determine the nature of the metabolites i n c o t t o n , rice paddy and its environment i n order to evaluate t h e i r similarities or dissimilarities w i t h the r a t m e t a b o l i t e s . T h i s information is needed by the t o x i c o l o g i s t i n determining the s i g n i f i c a n c e of the metabolites as r e s i d u e s . *
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I
II
*Denotes carbon-14 l a b e l . 1
Current address: Mobil Chemical Company, R&D, Crop Chemicals Department, P.O. Box 1028, Princeton, N J 08540.
0097-6156/81/015 8-0097$05.00/ 0 © 1981 American Chemical Society
Rosen et al.; Sulfur in Pesticide Action and Metabolism ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
98
SULFUR
IN
PESTICIDE
ACTION
AND
METABOLISM
Metabolism i n Rats 1. Phosfolan. When twelve male Royal Hart Wister r a t s were given a s i n g l e o r a l dose of *C-phosfolan i n peanut o i l a t l m g A g or 2 mg/kg, which i s equivalent to 10 or 20 ppm i n the feed and housed i n Delmar-Roth metabolism cages f o r c o l l e c t i o n of r e s p i r a t i o n gases and e x c r e t a , they excreted approximately 50% of the administered r a d i o a c t i v i t y and r e s p i r e d about 20% as C02 within 144 h (Table I ) . The r a d i o a c t i v e residues i n the v a r i o u s t i s s u e s were found to be d i s t r i b u t e d throughout the body w i t h lower concentrations r e s i d i n g i n f a t and muscle (Table I I ) . Chromatographic a n a l y s i s of u r i n a r y and t i s s u e r a d i o a c t i v i t y showed the presence of only one s i g n i f i c a n t m e t a b o l i t e , which was i d e n t i f i e d as thiocyanate i o n . 1
LU
•l . ι iTTVITn'^'TV'rl'hfvv^ ι
M/E
50
100
100
Ι Γ Ι Μ Μ Ι
150
ι
200
l'MHl'
250
300
(B)
N
S"
C H
2
134
co ζLU I-
5 50 LU >
LU
τ ; u'n ' 1
M/E 50
100
150
I ' » ' I ' I ' I ' I ' I ι | ' I ' I ' M
200
250
I
' r
300
Journal of Agricultural a n d Food Chemistry
Figure 5. Cl{CH ) mass spectrum of cyclic S,S-propylene dithiocarbonate (A) C imido-labeled and (B) C ethyl-labeled mephosfolan photolysates k
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Rosen et al.; Sulfur in Pesticide Action and Metabolism ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
SULFUR
108 Table V I I .
IN
PESTICIDE
ACTION
AND
METABOLISM
Recovery of mephosfolan-derived r a d i o a c t i v i t y from g o l d f i s h reared i n r i c e paddy environment i n a greenhouse. *
Exposure Time (Weeks )
Concentration (ppm) Unextracted Extractable
Total
lh
0.30 0.09 0.05 0.16
1.06
1.36
lk
0.21 0.05
1.0
1.2
0.26 0.04 Trace 0.22
0.42
0.68
1
Total C Mephosfolan SCN i o n Unidentified
3
Total C Mephosfolan SCN i o n Unidentified**
0.11
5
Total C Mephosfolan SCN i o n Unidentified
7
Total
1£f
C
0.20
0.57
0.77
9
Total
l H
C
0.11
0.27
0.38
1 4
* F i s h were placed i n t r e a t e d paddy water 1 week a f t e r treatment. * * C o n s i s t s of 22 spots; l a r g e s t 0.008 ppm. the s i g n i f i c a n c e o f the r e l a t i v e l y minor p e s t i c i d e uptake by the f i s h when reared i n the paddy environment. Metcalf e t . a l . (5) and Kapoor e t . a l . (6) have defined the e c o l o g i c a l m a g n i f i c a t i o n constant as the r a t i o o f the concentrat i o n o f parent compound i n the organism v s . the c o n c e n t r a t i o n of parent compound i n water. The bio-accumulation constant i s d e f i n e d as the r a t i o o f the t o t a l r a d i o a c t i v i t y c o n c e n t r a t i o n i n the organism v s . the t o t a l r a d i o a c t i v i t y c o n c e n t r a t i o n i n water. The authors obtained data f o r DDT and methoxychlor i n a t e r r e s t r i a l aquatic model ecosystem where the p e s t i c i d e was a p p l i e d t o t e r r e s t r i a l f o l i a g e only. The f i s h were kept i n t h i s system f o r three days and the highest v a l u e f o r e c o n o l o g i c a l m a g n i f i c a t i o n constant f o r DDT was 84500 and f o r bioaccumulation was 13500. The comparative f i g u r e s f o r methoxychlor, a biodegradable p e s t i c i d e , were 1545 and 206, r e s p e c t i v e l y . Although i t i s
Rosen et al.; Sulfur in Pesticide Action and Metabolism ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
7. KU AND KAPOOR
Dithiolane Insecticides
109
d i f f i c u l t to compare t h i s study w i t h those u s i n g the M e t c a l f system, due to the d i f f e r e n c e s i n the two systems, we can examine and compare t h e i r data w i t h the mephosfolan sutdy i n which f i s h were exposed f o r one week i n the paddy environment. From a s t a r t i n g c o n c e n t r a t i o n o f 0.16 ppm, an e c o l o g i c a l m a g n i f i c a t i o n of 0.56 and a bioaccumulâtion of 8.5 were found f o r f i s h exposed to mephosfolan. Since very low values of e c o l o g i c a l m a g n i f i c a t i o n (0.56 v s . 84500 f o r DDT) were obtained, i t i s evident that mephosf o l a n i s not l i k e l y to cause any e c o l o g i c a l o r bioaccumulation hazards when i t i s used i n a rice-paddy environment. Abstract 14
The metabolism of two C-dithiolaneinsecticides labeled in the imido carbon position was investigated in rats, cotton plants and a simulated rice paddy environment. Analysis of urine from rats treated with C-mephosfolan, or C/ C mixture mephosfolan by preparative and thin-layer cochromatography with synthetic standards and by mass spectroscopy showed that the attack occurs at the methyl moiety of the dithiolane ring resulting in a carboxylate ions. Hydrolysis of the P-N bond succeeded by ring opening results in release of the thiocyanate ion. This latter pathway is also the only metabolic route for phosfolan. For both insecticides, the predominant tissue metabolite was found to be the thiocyanate ion. When cotton plants were treated, mephosfolan was the predominant radioactive residue. Hydroxylation of the methyl moiety of the iminodithiolane ring and conjugation as glucoside was a significant pathway. Upon treatment of the rice paddy environment with mephosfolan, it was observed that the rice plants assimilate mephosfolan rapidly, degrade it and incorporate the C-carboninto the natural plant products. Fish kept in the paddy environment readily metabolized mephosfolan into thiocyanate and many polar metabolites. The major products of photodegradation of mephosfolan were cyclic S,S-propylene dithiocarbonate, 2-imino5-methyl-1,3-dithiolane, and diethyl phosphate. Minor products were ethyl phosphate and phosphoric acid. 14
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Literature Cited 1. 2. 3. 4.
S i e g e l , J . R., Rosenblatt, D. H., J . Am. Chem. Soc. (1958), (80), 1753. Addor, R. W., J . H e t e r o c y l . Chem. (1970), 7, 381. W i l l i a m s , R. T., " D e t o x i f i c a t i o n Mechanisms", Wiley, New York, N.Y., (1959). Z u l a l i a n , J . , B l i n n , R. C., J . A g r i c . Food Chem. (1977), 25, 1033.
5.
M e t c a l f , R. L., Sangha, G. K., Kapoor, I. P., Environ. Sci. Technol. (1971), 5, 709.
6.
Kapoor, I. P., M e t c a l f , R. L., Hirwe, A. S., Coats, J. R. Khalsa, M. S., J . A g r i c . Food Chem. (1973), 21, 310.
RECEIVED February 19, 1981.
Rosen et al.; Sulfur in Pesticide Action and Metabolism ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
