Pesticide Chemistry and Regulation in the People's Republic of China

34

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Pesticide Chemistry and Regulation in the People's Republic of China ZHENG-MING LI (CHENG-MING LEE)

1

Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, People's Republic of China

Development of Pesticide Chemistry in China In comparison with the United States, China has similarities in size of territory, and geographical latitude. But China has a population of 1 billion (4.5 times that of the U.S.) and a harvested land of 100 million hectares (about 80% of that of the U.S.). China grows rice which comprises nearly half of the national grain production in the southern provinces, while in the northern provinces wheat, corn, millet and sorghum are produced. Due to nation-wide irrigation construction, popularization of high-yielding seeds, usage of futilizer and pesticides, and intensive cultivation, China has made great strides in providing adequate food for her large population. In 1979, China's grain output reached 324.9 million tons, the output of oil-bearing crops topped 6.43 million tons, and of cotton amounted to 2.2 million tons (1). In these achievements, the research and development of Pesticide Chemistry has contributed its part. The pest s i t u a t i o n i n China i s somewhat d i f f e r e n t from that i n the United S t a t e s . Some of the major pests are l i s t e d below:

1

Insects:

r i c e paddy borer (Tryporuza i n c e r t u l e s Walker) p l a n t hopper ( N i l a p a r v a t a lugens s t a l ) leafhopper (Nephotettix c i n c i t i c e p s Uhler) wheat armyworm (Leucania separata Walker) corn borer ( O s t r i n i a n u b i l a l i s Hubner) cotton aphid (Aphis g o s s y p i i Glover) cotton bollworm ( H e l i o t h i s armigera Hubner)

Fungi:

Rice b l a s t ( P i r i c u l a r i a oryzae Cavara) Rice b a c t e r i a l b l i g h t (Xanthomonas oryzae Dowson) Sheath b l i g h t of r i c e ( P e l l i c u l a r i a s a s a k i i ( S h i r a i ) S. I t o )

Current address: Visiting Scientist, OCSL, AEQI, USDA, Beltsville, MD 20705.

This chapter not subject to U.S. copyright. Published 1981 American Chemical Society Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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Fusarium w i l t of cotton (Fusarium vasinfectum Atk.) Wheat r u s t ( P u c c i n i a t r i t i c i n a E r i k s s o n , and P u c c i n i a glumarum (Schmidt) E r i k s s o n et Henning)


Weeds:

Nutgrass f l a t s e d g e (Cyperus rotundus Linnaeus) Barnyard grass (Echinochloa c r u s g a l l i (L.) Beauvois) Wild oat (Avena f a t u a Linnaeus) Cogangrass (Imperata c y l i n d r i c a (L.) Beauvois) Bermuda grass (Cynodon dactylon Persoon)

Due to the requirements of the expanding a g r i c u l t u r e i n China, p e s t i c i d e i n d u s t r y has now grown from v i r t u a l l y n i l before the l i b e r a t i o n i n 1949 i n t o l a r g e - s c a l e production. I t was reported that p e s t i c i d e production i n China i n 1977 was probably 500,000 tons ( i n gross weight) (2). Though many p e s t i c i d e s a r e produced i n terms of l a r g e tonnage, the supply can only meet about 60% of the present demand. Following i s a p a r t i a l l i s t of the p e s t i c i d e s produced i n China ( s t r u c t u r e s of p e s t i c i d e s of Chinese o r i g i n are shown i n Table I . ) : Insecticides Organic CI:

BHC (benzene h e x a c h l o r i d e ) , l i n d a n e , DDT, toxaphene, t e t r a d i f o n

Organic P:

E t h i o n , phorate (Thimet), p a r a t h i o n , methylparathion, demeton, t r i c h l o r f o n ( D i p t e r e x ) , d i c h l o r v o s (DDVP), dimethoate (Rogor), Malathion, phosphamidon

Carbamates :

carbaryl

(Sevin)

Fungicides EMC ( e t h y l mercuric c h l o r i d e ) , DD mixture, HCB (hexachlorobenzene), PCNB, Ambam (diammonium ethylene b i s ( d i t h i o c a r b a m a t e ) ) , Zineb, Urbazid (methylarsine b i s ( d i m e t h y l d i t h i o c a r b a m a t e ) ) , Captan, C a p t a f o l , Asozine methylarsine s u l f i d e , p-aminobenzene s u l f o n i c acid 401, Jingangmycin, Duo-Jun-Ling H e r b i c i d e s and Plant Growth Regulators PCP, H e r b i c i d e no. 1, n i t r o f e n , 2,4-D, dalapon, p r o p a n i l , NAA, 920 ( g i b b e r e l l i n s ) , MCPA, Ethephon Since the f i f t i e s , many research i n s t i t u t i o n s i n China have screened about 10,000 of t h e i r s y n t h e t i c compounds and new

Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.


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a n t i b i o t i c s i n bioassays. Many candidate p e s t i c i d e s have gone under d i f f e r e n t t e s t s , and some of the p e s t i c i d e s shown i n Table I have gone i n t o production. These are China's f i r s t e f f o r t s a t o r i g i n a t i n g her own p e s t i c i d e s to adapt to her p e c u l i a r needs. In recent years, c e r t a i n research groups i n China have a l s o been a c t i v e i n the f i e l d s as i n s e c t pheromones (3), p y r e t h r o i d s and n a t u r a l b i o - a c t i v e products. Nevertheless, they are i n the stage of research and development rather than l a r g e - s c a l e production. At the present 90% o f a l l p e s t i c i d e s produced i n China a r e i n s e c t i c i d e s , but recent emphasis has been placed on the research and development of f u n g i c i d e s , h e r b i c i d e s , and p l a n t growth r e g u l a t o r s . China a l s o imports new p e s t i c i d e s from abroad to supplement some of her s p e c i a l needs. The Impact of Modern Toxicology From Rachel Carson's " S i l e n t Spring" (15) published i n 1963 as a t u r n i n g p o i n t , many e n v i r o n m e n t a l i s t s have become much concerned with the environmental p o l l u t i o n a r i s i n g from the widespread use of p e s t i c i d e s . Since then, many c o u n t r i e s , i n c l u d i n g China, have strengthened t h e i r c o n t r o l over the r e g u l a t i o n o f p e s t i c i d e s . Today r e s e a r c h on p e s t i c i d e chemistry not only i n v o l v e s the c o l l a b o r a t i v e e f f o r t s of chemists and b i o l o g i s t s , but a l s o that of biochemists, pharmacologists, t o x i c o l o g i s t s and environmental s c i e n t i s t s . It might be b e n e f i c i a l to review some development stages of p e s t i c i d e chemistry i n China. In the m i d - f i f t i e s , when h i g h l y a c t i v e organic-phosphorus i n s e c t i c i d e s were f i r s t introduced to the market, t h e i r l a r g e - s c a l e production was encouraged notwithstanding the f a c t that many of them are h i g h l y t o x i c substances. Many " h i g h l y a c t i v e , h i g h l y t o x i c " p e s t i c i d e s a c t u a l l y went i n t o production, and only acute t o x i c i t y data was r e q u i r e d at that time. In the s i x t i e s , due to the growing awareness o f some s e r i o u s a c c i d e n t s that occured during the handling of these h i g h l y t o x i c substances, the preference was s h i f t e d g r a d u a l l y to produce new " h i g h l y a c t i v e , low t o x i c " p e s t i c i d e s . Besides the acute t o x i c i t y data, subchronic data emerged as an important problem. Thus some r e l a t i v e l y l o w - t o x i c i t y p e s t i c i d e s came i n t o production i n place of some o l d ones. S t a r t i n g i n the s e v e n t i e s , due to the r a p i d advances i n the f i e l d o f t o x i c o l o g y , s e v e r a l n a t i o n a l p e s t i c i d e conferences were h e l d i n China to d i s c u s s g u i d e l i n e s f o r the f u t u r e development of p e s t i c i d e s . New p e s t i c i d e s have been r e q u i r e d to be " h i g h l y a c t i v e , h i g h l y s e l e c t i v e , low r e s i d u a l , l e s s expensive". Checking r e s i d u a l e f f e c t s on nontarget organisms has been g r e a t l y emphasized. Now for every new p e s t i c i d e comprehensive c a r c i n o g e n i c , mutagenic and t e r a t o g e n i c data must be submitted before production. An i n t e g r a t e d Pest Management (IPM) p o l i c y has been o f f i c i a l l y announced and i s g r e a t l y encouraged. A l l kinds of c u l t u r a l and b i o l o g i c a l c o n t r o l methods have a l s o been p o p u l a r i z e d nation-wide



P47

401

Duo-Jun-Ling

Ai-Jian-Su

Di-Ku-Shuang

Jinggangmycin

1958

1958

1970

1971

1971

1973

v

;

!

5

2

A,

-Ν

2

ο

5

2

2

4

2

5

F

I

2

CI

2

2

3

" CH ~

3

+ CH -| CH =C-CH N ^-CH3 | C I " PGR

- '^N^NHC-0CH3 H

; !

2

5

C H SSC H

2

2

Usage

(C H 0) PSCH OC H SC H

3

Formula S ..H - ~ \ ( C H ) N C N < ^ )C1

antibiotics

i_

1

Ν Ν il I'; 'i I \ g NHCH NH- ·;

H e r b i c i d e no. 1

1958

(b)

P e s t i c i d e Name

Year Discovered

(a)

(9)

(8)

(7)

(5_>.§)

(4)

Reference

Shanghai P e s t i c i d e Res. I n s t .

(11)

Sichuan P e s t i c i d e Res. I n s t . , Sichuan (10) Res. Inst, of Chem. Eng.

Nankai Univ.

Shen-Yang Chem. Eng. Res. I n s t . , Shanghai P e s t i c i d e Res. I n s t .

Res. Inst, of Organic Chemistry (Shanghai)

Nankai Univ.

Nankai Univ.

Institution

Table I. P e s t i c i d e s developed i n China


ο r ο ο •
σ

m

W Ο X

5

Q

H

C/3

w *d m

H X

to


d.

c.

b.

a.

1977

771-2CT

;

Sha-Chung-Shuang 2

2

3

S

S 2

NjH^SSC^Na

2

5

(C2H5O) P-S-S-P(OC H )

3

(CH ) N-CH

2

F

I

Guizhou Chem. Eng

Nankai Univ.

Res. I n s t .

(±2,14)

(12)

In t h i s column, H = h e r b i c i d e , I = i n s e c t i c i d e , F = f u n g i c i d e s , and PGR = p l a n t growth regulators. Though the acute t o x i c i t y of P47 i s lower than Demeton, due to higher production cost of P47 i t s development was stopped. Due to the u n s a t i s f a c t o r y r e s u l t s of 2-year chronic t o x i c o l o g i c a l t e s t s , i t s production was d i s c o n t i n u e d . A c t i v i t y against b a c t e r i a l l e a f b l i g h t of r i c e was discovered. I t i s undergoing l a r g e s c a l e f i e l d t e s t s and chronic t o x i c i t y examination.

1974

CH SS0 Na


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(16,17,18). Production, storage and a p p l i c a t i o n of mercuryc o n t a i n i n g p e s t i c i d e s have been s t r i c t l y p r o h i b i t e d . T i n and A r s e n i c - c o n t a i n i n g p e s t i c i d e s have been discarded. Organoc h l o r i n e p e s t i c i d e s have been g r e a t l y r e s t r i c t e d and are g r a d u a l l y being phased out. Though some were reported r e c e n t l y to cause delayed n e u r o t o x i c i t y , other organophosphorus and carbamate p e s t i c i d e s are s t i l l considered to be acceptable due to the r e l a t i v e ease with which they are degraded b i o l o g i c a l l y and chemically. The Regulation of P e s t i c i d e s P e s t i c i d e r e g u l a t i o n became complicated when chronic t o x i c o l o g i c a l problems stepped i n t o the p i c t u r e . In 1974 when the N a t i o n a l P e s t i c i d e Information Conference was h e l d i n China, Wuhan Medical College presented t h e i r own t o x i c o l o g i c a l data about an imported l o w - t o x i c i t y f u n g i c i d e d i c h l o z o l i n e ( S c l e x ) , [3-(3,5-dichlorophenyl)-5,5-dimethyl-2,4-oxazolidinedione]. In t h e i r chronic t e s t s , they confirmed that d i c h l o z o l i n e could cause c a t a r a c t s and induce malignant tumors i n experimental mice. Subsequently there was the chlordimeform (Fundal) case. At that time Chinese s c i e n t i s t s were t r y i n g to use the l o w - t o x i c i t y chlordimeform (Fundal), [N -(4-chloro-o-tolyl)-N,N-dimethyl formamidine] to r e p l a c e the t r a d i t i o n a l organochlorine i n s e c t i cides i n combating r i c e paddy borers. Reports from abroad that chlordimeform was p o s s i b l y c a r c i n o g e n i c s u r p r i s e d everyone and the a p p l i c a t i o n of chlordimeform was a b r u p t l y stopped. These two events spurred the Chinese workers to s t a r t t h e i r own t o x i c o l o g i c a l research. Later a s e r i e s of n a t i o n a l conferences were h e l d . In 1976, the N a t i o n a l Forum on P e s t i c i d e Toxicology and Residues was h e l d . In 1978, the M i n i s t r y of Chemical Engineering, the M i n i s t r y of A g r i c u l t u r e and the M i n i s t r y of P u b l i c Health c a l l e d f o r a n a t i o n a l meeting to d i s c u s s the t o x i c o l o g y and residue problems of p e s t i c i d e s and f i n a l l y d r a f t e d "Proposed Regulations of Experimental Methods f o r P e s t i c i d e Toxicology" (19) and "Proposed Regulations f o r P e s t i c i d e Toxicology and Residues" (20). T h i s was an attempt f o r the f i r s t time i n China to standardize the methodology i n v o l v e d i n the t o x i c o l o g i c a l t e s t s . Soon a f t e r another paper "Proposed Regulations of T o x i c i t y Experiments f o r F i s h e s " was a l s o d r a f t e d (21). In A p r i l 1980, a d e c i s i v e step was taken j o i n t l y by the M i n i s t r y of A g r i c u l t u r e , the M i n i s t r y of Chemical Engineering, the M i n i s t r y of P u b l i c Health, and the Environmental P r o t e c t i o n Agency (an o r g a n i z a t i o n d i r e c t l y r e s p o n s i b l e to the State C o u n c i l ) . A f t e r c o n s u l t i n g with the s p e c i a l i s t s and p r a c t i t i o n e r s concerned, the four departments j o i n t l y d r a f t e d out the "Regulations f o r P e s t i c i d e Management" (22). At present i t i s submitted to State C o u n c i l f o r f i n a l promulgation. It w i l l be the l e g a l b a s i s f o r r e g u l a t i n g and monitoring the research production and a p p l i c a t i o n of a l l p e s t i c i d e s i n the future. f



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The "Regulations f o r P e s t i c i d e Management" c o n s i s t s o f three parts: (a) processing of a p p l i c a t i o n s f o r p e s t i c i d e r e g i s t r a t i o n s , (b) r u l e s o f q u a l i t y c o n t r o l o f p e s t i c i d e s , and (c) r u l e s of safe a p p l i c a t i o n of p e s t i c i d e s . According to the new r e g u l a t i o n s , the a p p l i c a t i o n f o r r e g i s t r a t i o n of any new p e s t i c i d e must f i r s t be submitted to the I n s t i t u t e f o r the C o n t r o l l i n g of P e s t i c i d e s , an a u t h o r i t a t i v e s t a t e o r g a n i z a t i o n subordinated to the M i n i s t r y of A g r i c u l t u r e . This I n s t i t u t e w i l l review the submitted s e c t i o n s on b i o a c t i v i t y , p h y t o t o x i c i t y and residues on behalf of the M i n i s t r y of A g r i c u l ture. A l l the other data w i l l be sent simultaneously to the M i n i s t r y of Chemical Engineering (MCE), the M i n i s t r y of P u b l i c Health (MPH) and Environmental P r o t e c t i o n Agency (EPA) f o r j o i n t review. The MCE w i l l s c r u t i n i z e the r e l a t e d production technology, a n a l y t i c a l methods, waste management, e t c . The MPH w i l l probe i n t o the t o x i c o l o g y problem i n d e t a i l , and the EPA w i l l examine the p e s t i c i d e p o l l u t i o n on s o i l , water system, and a i r . Only a f t e r a l l the data are c l e a r e d f o r f i n a l approval from these M i n i s t r i e s can the formal r e g i s t r a t i o n be granted by the M i n i s t r y of A g r i c u l t u r e . (Step D-F) In applying f o r r e g i s t r a t i o n of a candidate p e s t i c i d e , there a r e s t i l l more steps to go through; the whole process i s shown schematically below i n Figure 1. (Step A-H)· When an o r g a n i z a t i o n , be i t i n d u s t r y , u n i v e r s i t y o r research i n s t i t u t i o n , has a candidate p e s t i c i d e , the f i r s t step a f t e r the minimum research i s completed (Step A) i s to f i l e an a p p l i c a t i o n for a P r e l i m i n a r y T e c h n i c a l A p p r a i s a l Conference (Step B). At t h i s conference, organized by the appropriate n a t i o n a l o r l o c a l a u t h o r i t i e s , an s t e e r i n g a p p r a i s a l committee w i l l be s e t up. The committee i s composed of r e p r e s e n t a t i v e s i n v i t e d from n a t i o n a l or p r o v i n c i a l organizations of Science and Technology, Chemical Engineering, A g r i c u l t u r e , Environmental P r o t e c t i o n , a g r i c u l t u r e research i n s t i t u t i o n s , medical i n s t i t u t i o n s , occupational hygiene research i n s t i t u t i o n s , Academy of Science, u n i v e r s i t i e s and other concerned bodies. These r e p r e s e n t a t i v e s w i l l examine c a r e f u l l y a l l the reports which must i n c l u d e : (a) (b) (c) (d) (e)

Background Comparison of d i f f e r e n t s y n t h e t i c routes A n a l y t i c a l methods Bioassay r e s u l t s of greenhouse and t e s t p l o t s Acute and subchronic t o x i c i t y data ( i t was affirmed r e c e n t l y (19,20) that subchronic teratogenic and mutagenic data should be included. For organophosphorus compounds, delayed n e u r o t o x i c i t y t e s t i n g i s required. Residue a n a l y s i s i n food crops, forage, p o u l t r y , animals and aquatics b i o t a i s a l s o needed) (f) Experimental waste d i s p o s a l



530

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Laboratoryl ν Preliminary T e c h n i c a l ^ Intermediate T e c h n i c a l A p p r a i s a l Conference A p p r a i s a l Conference work

M i n i s t r y of Chemical Engineering

I n s t i t u t e f o r the| C o n t r o l l i n g of Pesticides D

M i n i s t r y of Agriculture ^. (formal . ^registration) I

M i n i s t r y of P u b l i c Health

Environmental Protection^ Agency

M i n i s t r y of Chemical Engineering

Figure 1.

____________

Production

Steps involved in the registration of a candidate pesticide



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Only a f t e r a l l the r e p o r t s a r e discussed, i n q u i r i e s and suggestions a r e made and the research work i s evaluated as acceptable and s a t i s f a c t o r y w i l l a P r e l i m i n a r y A p p r a i s a l C e r t i f i c a t e be d r a f t e d and signed by every r e p r e s e n t a t i v e and the c h i e f p r a c t i t i o n e r s who are r e s p o n s i b l e f o r the r e p o r t s . To reach t h i s stage u s u a l l y take 1-3 years. With t h i s formal step completed, f u r t h e r f i n a n c i a l support can be sought f o r a d d i t i o n a l research work, which o f t e n takes 2-4 more years ( f i e l d t e s t s and chronic t o x i c o l o g y t e s t s r e q u i r e data f o r 2 successive y e a r s ) . Then a l l r e p o r t s have to submit i n t o the a u t h o r i t i e s concerned to request an Intermediate T e c h n i c a l A p p r a i s a l Conference. A l a r g e r group of r e p r e s e n t a t i v e s from a l l the r e l a t e d f i e l d s w i l l be i n v i t e d to examine and s c r u t i n i z e a l l the d e t a i l s of the r e p o r t s . These r e p o r t s should i n c l u d e the f o l l o w i n g : (a) (b) (c) (d)

(e) (f) (g) (h)

(i)

P i l o t p l a n t t e s t runs I n d u s t r i a l a n a l y t i c a l methods Bioassay i n l a r g e demonstration and i n productive f i e l d tests Subchronic and chronic t o x i c o l o g i c a l data (subchronict o x i c i t y t e s t s , 3 months; c h r o n i c - t o x i c i t y t e s t s 2 years. C h r o n i c - t o x i c i t y t e s t s i n c l u d e c a r c i n o g e n i c i t y and reproduction t e s t s (3 g e n e r a t i o n s ) , residue dynamics, and metabolism and degradation data (metabolism t e s t s i n animals w i l l be r e q u i r e d a f t e r 1980) Formulation data S t a n d a r d i z a t i o n of product, and i m p u r i t i e s and residue allowances Waste management t e s t runs on p i l o t p l a n t Standard measures f o r o c c u p a t i o n a l hygiene, d e t o x i f i c a t i o n and s a f e t y , the determination of ADI, (Acceptable D a i l y Intake), e t c . C a l c u l a t i o n of production costs

Many questions and requirements w i l l be r a i s e d at t h i s p o i n t . Another Intermediate A p p r a i s a l C e r t i f i c a t e has to be signed i n a s i m i l i a r manner. Then a l l the documents, r e p o r t s , and c e r t i f i c a t i o n s a r e sent to the M i n i s t r i e s (Step D and E) f o r j o i n t review and approval. Only a f t e r the formal l e g i s t r a t i o n i s granted (Step F) can the chemicals and equipments be disbursed from the M i n i s t r y o f Chemical Engineering (Step G). The design and m a t e r i a l i z a t i o n o f t h i s p r o j e c t w i l l take probably another 1-3 years before the new p e s t i c i d e f i n a l l y goes i n t o production (Step H). These r a t h e r complicated steps a r e s e t up to r e g u l a t e new p e s t i c i d e s properly and assure the utmost b e n e f i t to the people. For example, a f t e r g e t t i n g through Step A-C, the required papers f o r the new i n s e c t i c i d e Sha-Chung-Shuang (see Table I) are now being submitted to the I n s t i t u t e f o r the C o n t r o l l i n g of P e s t i c i d e s f o r f u r t h e r review (23).



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The above procedure i s a p p l i e d p r i m a r i l y to the new p e s t i cides or the o l d p e s t i c i d e s with new formulations. I t w i l l g r a d u a l l y cover the r e - r e g i s t r a t i o n of the o l d e r p e s t i c i d e s already i n use. R e g i s t r a t i o n f o r imported p e s t i c i d e with r e l i a b l e chronic t o x i c i t y data w i l l be granted f o r f i e l d a p p l i c a t i o n . However i n the case of d i c h l o z o l i n e mentioned above, Chinese workers confirmed i t s c h r o n i c - t o x i c i t y problems with t h e i r own data and decided l a t e r to d i s c o n t i n u e i t s use in China. As c o n d i t i o n s r e q u i r e , the above sequence of p r o c e s s i n g can be stopped at any step. Take Di-ku-Shuang (DKS) (see Table I) f o r example. I t i s a new f u n g i c i d e developed i n the e a r l y iventies by Sichuan P e s t i c i d e Research I n s t i t u t i o n . I t has c * a e x c e l l e n t systemic e f f e c t on b a c t e r i a l l e a f b l i g h t of r i c e , which i s ranked as one of the major crop diseases i n China. A f t e r much research work, i t s s y n t h e t i c steps are w e l l worked out and i t s production cost i s found as reasonable. I t s acute t o x i c i t y i s r a t h e r low. ( L D 5 0 f o r mouse o r a l : 2250 mg/kg; dermal: 150 mg/mg). It has a s k i n i r r i t a t i o n as s i d e e f f e c t . Many formulations were t r i e d , and a paste formulation was developed to avoid the s k i n i r r i t a t i o n during f i e l d a p p l i c a t i o n . It passed the P r e l i m i n a r y A p p r a i s a l Conference. Then many i n s t i t u t i o n s cooperated to carry i t through the f o l l o w i n g stages of development, and i n t e n s i v e e f f o r t s were i n v o l v e d i n the succeeding two years to conduct p i l o t - p l a n t runs, f i e l d t e s t s and chronic t o x i c i t y t e s t s ( i n c l u d i n g autopsy and h i s t o p a t h o l o g y work on s e v e r a l non-rodent s p e c i e s ) . Results showed no c a r c i n o genic e f f e c t s , but u n f o r t u n a t e l y i t was found during the reproduction t e s t s to have a t e r a t o g e n i c e f f e c t on f e t a l mice (24).

Despite the great need f o r new f u n g i c i d e s i n China and the c o n s i d e r a b l e investment and e f f o r t s poured i n t o i t , the DKS p r o j e c t was r e s o l u t e l y i n t e r r u p t e d a t Step C and i t s production was o f f i c i a l l y banned. Another new i n s e c t i c i d e Ming-Lin-Wei (an analogue of H e r b i c i d e no. 1, a l s o developed by Nankai U n i v e r s i t y ) had s a t i s f a c t o r y e f f e c t s on paddy r i c e borer and was promising as a replacement f o r the organochlorine i n s e c t i c i d e s . I t s acute o r a l t o x i c i t y i s L D 5 0 : 500 mg/kg ( r a t ) , 100 mg/kg (mouse). Sub-chronic t e s t s showed a f a v o r a b l e low accumulation. But i n t e r a t o g e n i c t e s t s , there i s a phenomenom of incomplete c a l c i f i c a t i o n of mouse sternum (25), so t h i s new i n s e c t i c i d e i s withheld temporally from production u n t i l more data are obtained. Some experts i n China argued r e c e n t l y that overemphasis on low t o x i c i t y might lead i n the wrong d i r e c t i o n , s i n c e lowt o x i c i t y f r e q u e n t l y r e f e r s to the a c u t e - t o x i c i t y data, which can not r e f l e c t the f u l l p i c t u r e i n c a r c i n o g e n i c , t e r a t o g e n i c and mutagenic c h a r a c t e r i s t i c s . Some l o w - t o x i c i t y p e s t i c i d e s as


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mentioned above (chlordimeform, d i c h l o z o l i n e , DKS, Ming-Lin-Wei) have chronic t o x i c i t y problems. Some h i g h l y t o x i c i n s e c t i c i d e s as a l d i c a r b (Temik), carbofuran, monocrotophos (Azodrin) could have t h e i r t o x i c i t y reduced by improvement i n f o r m u l a t i o n and s t i l l be used s a f e l y i n the f i e l d s . This i s the reason why acute t o x i c i t y should not be the prime c r i t e r i o n i n p e s t i c i d e r e g u l a t i o n today.


Perspective I t seems c l e a r now that modern t o x i c o l o g y has played a d e c i s i v e r o l e i n the f u t u r e development of the p e s t i c i d e chemi s t r y (26,27,28). Besides o n c o g e n i c i t y and t e r a t o g e n i c i t y , the importance of which has been f u l l y recognized, the metabolic pathways and the mutagenic e f f e c t s on r e p r o d u c t i o n are a l s o becoming the main c r i t e r i a i n assaying the t o x i c o l o g i c a l aspect of a l l p e s t i c i d e s . The s i t u a t i o n i s f u r t h e r complicated by the f a c t that when a p e s t i c i d e gets i n t o contact with the surrounding environment, under the i n f l u e n c e of s u n l i g h t and v a r i o u s enzymes e x i s t i n g i n d i f f e r e n t l i v i n g organisms ( i n s e c t s , mammals, p l a n t s , micro-organisms), v a r i o u s pathways w i l l produce many degradation products and m e t a b o l i t e s . Thus scores of new compounds with unknown t o x i c i t y w i l l be d e r i v e d from j u s t one simple s t r u c t u r e . Take two w e l l known types of f u n g i c i d e s f o r example. D i t h i o carbamates metabolize i n p l a n t s to form ethylene t h i o u r e a (ETU) which i s known f o r i t s c a r c i n o g e n i c i t y and t e r a t o g e n i c i t y ( f o r t u n a t e l y , ETU i s very s e n s i t i v e to UV l i g h t and i s degradable under s u n l i g h t ) . Another f u n g i c i d e , PCBA (Pentachlorobenzyl a l c o h o l ) , causes no chronic t o x i c problem i t s e l f , but i t can be changed by m i c r o b i a l metabolism i n the s o i l i n t o 1,2,5,6t e t r a c h l o r o b e n z o i c a c i d , which i s p h y t o t o x i c to f o l l o w i n g crops planted i n the same f i e l d . Thus we n o t i c e that i n such a d i v e r s i f i e d metabolic pathways i n d i f f e r e n t l i v i n g organisms, any one of these metabolites that has a s e r i o u s t o x i c i t y problem w i l l probably j e o p a r d i z e the p r a c t i c a l a p p l i c a t i o n of t h i s p e s t i c i d e , even though the p e s t i c i d e i t s e l f causes no t o x i c i t y problem at a l l . Since the pests possess the p e c u l i a r a b i l i t y to propagate tremendously and adapt s w i f t l y to the changing environment, we should b e l i e v e that p e s t i c i d e chemistry with i t s f l e x i b i l i t y and v e r s a t i l i t y s t i l l can play an important r o l e i n combating p e s t s . The p o i n t at argument i s not to d i s c a r d a l l the chemical p e s t i c i d e s , as some people have advocated, but to design and produce more a c t i v e , more s e l e c t i v e and more biodegradable k i n d of new chemical p e s t i c i d e s . Chemical p e s t i c i d e s have suppressed or e l i m i n a t e d many of the l e t h a l contagious d i s e a s e s , thus saving m i l l i o n s of human l i v e s , and c o n t r i b u t e d much to the g r e a t l y i n c r e a s e d output of farm produce. In human h i s t o r y , chemical p e s t i c i d e s should be honored f o r t h e i r achievements i n s t e a d of being t o t a l l y d i s c r e d i t e d . Although during the progress of



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p e s t i c i d e chemistry, there have r e g r e t t a b l y been some serious adverse e f f e c t s on the environment which were not f u l l y r e a l i z e d u n t i l many new a n a l y t i c a l and t o x i c o l o g i c a l techniques were developed i n the recent years. In the face of the discouragement caused by the e v e r - s t r i c t e r r e g u l a t i o n s and the high r i s k s i n volved i n the discovery and development of any new chemical p e s t i c i d e s , we should be aware of some of the promising f i e l d s (pheromones, j u v e n i l e hormones, p y r e t h r o i d s , amino-acid f u n g i c i d e s , phytoalexins, etc.) which have shown sound progress. There i s a l s o much room f o r improvement i n a p p l i c a t i o n and formulation technique f o r chemical p e s t i c i d e s to reduce the environmental p o l l u t i o n , since the major p o r t i o n of an a p p l i e d p e s t i c i d e often h i t s nontarget organisms rather than target pests. Any improvement i n methodology to s i m p l i f y the chronic t o x i c i t y t e s t s that can cut down the immense costs and amount of s c i e n t i f i c manpower involved w i l l c e r t a i n l y encourage the development of p e s t i c i d e chemistry. Modern a g r i c u l t u r e needs a new generation of p e s t i c i d e s to keep i n pace with the demands of the modern world. Today p e s t i c i d e chemistry i s entangled i n so many f i e l d s of science that i t can no longer be undertaken by small groups of s p e c i a l i s t s i n j u s t a few l i n e s of study. Only through p e r s i s t e n t and i n t e n s i v e b a s i c research i n c o l l a b o r a t i o n with a l l the s c i e n t i s t s concerned can we r i s e to the challenge ahead of us.

1. 2.

3. 4. 5. 6. 7. 8. 9. 10.

Literature Cited Oversea Press Release from Xinhua News Agency, April 8, 1980. Groen, H. J. and Kilpatrick, J. A. "China's Agricultural Production, Chinese Economy, Joint Economic Committee, U.S. Congress, Vol. 1. Policy Performance, A compendium of Papers"; U.S. Government Printing Office: Washington, D.C., Nov. 9, 1978; p. 635. Kiangsu Institute of Sericulture, Peking Institute of Zoology, Shanghai Institute of Organic Chemistry, Acta Entomology Sinica, 1974, 17, 290-302. He, Bing-Lin, Yang, Hua-Zheng, Acta Chimica Sinica, 1960, 26(1), 1-6. Yang, Shih-Hsien, Chen, Tian-Chi, Lee, Cheng-Ming, Li, Yu-Kwei, Wang, Chin-Sun, Yan, Mun-Gong, Dung, Shi-Yang, Scientia Sinica, 1960, IX (7), 897; C.A. 54 19467 (1960). Yang, Shih-Hsien, Chen, Tian-Chi, Lee, Cheng-Ming, Li, Yu-Kwei, Tung, Hsi-Yang, Kao, Shou-Yi, Tung, Sung-Chi, Acta Chimica Acta, 1962, 28(3), 187; C.A. 59 3758 h (1963). Li, Zheng-Ming, Pesticide Industry Technical Journal, 1978, 2, 16. Jiang, Shao-Ming, Huan Ching Ko Hsueh (Environmental Science) 1978, 12, 22. Res. Inst, of Elemento-Organic Chemistry, Huaxue Tongbao (Chemical Review), 1974, 1, 37. Sichuan Pesticide Res. Inst., Pesticides, 1973, 4, 21.



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11. Shanghai Pesticide Res. Inst., Pesticide Research Informa tion, 1974, 4; 1974, 6. 12. Data taken from an unpublished report by Guizhou Chem. Eng. Res. Inst., "A new nereistoxin-type insecticide Sha-ChungShuang" May, 1979. 13. Yang, Shih-Hsien, Chen, Tian-Chi, Tang, Chu-Chi, Jin, Gui-Yu, Liu, Tian-Lin, Zhang, Jin-Pei, Pesticide Industry, 1966, 1, 28. 14. Res. Inst. of Elemento-Organic Chemistry, Pesticide Industry, 1979, 3, 34. 15. Carson, R., "Silent Spring", Hamish Hamilton, London, 1963. 16. American Insect Control Delegation, "Insect Control of People's Republic of China" (CSCPRC Report no. 2); National Academy of Sciences: Washington, D.C., 1977. 17. American Plant Studies Delegation, "Plant Studies in the People's Republic of China" (CSCPRC Report); National Academy of Science: Washington, D.C., 1975. 18. Klassen, W., "Notes on trip to People's Republic of China of U.S. Biological Control Team" July 5-31, 1979, BARC, USDA, unpublished. 19. Proposed Regulations of Experimental Methods for Pesticide Toxicology, (Zhejiang conference, 1978, unpublished). 20. Proposed Regulations for Pesticide Toxicology and Residues (ibid.). 21. Proposed Regulations of Toxicity Experiments for Fishes (including Embryotoxicity Testing Methods), (drafted by National Aquatic Department of the P.R.O.C., 1979, unpublished). 22. Regulations of Pesticide Management (April 1980, unpublished). 23. Toxicological data for Sha-Chung-Shuang complied by Gui-Yang Medical College, Shanghai 1st Medical College, Gui-Zhou Provincial Sanitary Station, Jian-Su New Medical College (May, 1979, unpublished). 24. Sichuan Provincial Sanitary Station, "The Toxicology Research on Di-Ku-Shuang (Ν,Ν'-methylene bis(1,3,4thiadiazole-2-amine)" (August 1979, unpublished). 25. Res. Inst, of Elemento-Organic Chemistry, Nankai Univ., "Ming-Lin-Wei Intermediate Technical Appraisal Conference Data" (Conference held in Zhengjiang, Jiang-Su in May, 1979, unpublished). 26. Yang, Shih-Hsien, Liu, Lun-Zhu, Li, Zheng-Ming, Chen, Ru-Yu, "Advance of Pesticides" Vol. II; Chem. Eng. Publ. Hse.: Peking, 1979; p. 11, p. 83. 27. Environmental Protection Agency, Registration of Pesticides in the United States (Proposed Guidelines). Federal Register Part II (July 10, 1978) pp. 29690-29741. 28. Environmental Protection Agency, Pesticide Programs (Proposed Guidelines for Registering Pesticides in the U.S.); Hazard Evaluation : Humans and Domestic Animals. Federal Register, Part II (Aug. 22, 1978), pp. 37336-37403. RECEIVED March 10, 1981. Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

Pesticide Chemistry and Regulation in the People's Republic of China

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