bk-1979-0111.ch011

11 Factors Affecting Commercialization of Specialty-Use Plant Growth Regulating Chemicals A L D O J. CROVETTI

Downloaded by UNIV LAVAL on July 10, 2016 | http://pubs.acs.org Publication Date: September 27, 1979 | doi: 10.1021/bk-1979-0111.ch011

Agricultural Chemicals Research, Chemical and Agricultural Products Division, Abbott Laboratories, North Chicago, IL 60064

Plant growth regulators, whether natural occurring or synthetic have been used commercially since the 1950's. Their uses have generally been to modify growth, enhance yields of food and fiber, adapt plants to scheduled harvest patterns and make certain crops more adaptable to mechanical harvesting. The progress with plant growth regulators has taken us through the periods of auxins, maleic hydrazide, the gibberell i n s , cytokinins, abscisic acid to the newer generation of ethylene releasers and ripeners. The major plant growth regulators i n use include Alar (apples and cherries), MH-30 (tobacco), other sucker control agents, ethephon for a variety of uses, gibberellic acid, CCC (grains) and Polaris® (sugarcane) (1, 2, 3, 4). There are an estimated two-three million acres of U.S. cropland treated with plant growth regulators (5). This i s not a large treatment pattern when considering cotton, corn, peanuts and soybeans total 144 million acres. Of the 20-30 formulated products available, the growth regulators mentioned account for >90% of the current market. Tobacco accounts for one-half the consumption with apples a close second, employing chemicals for thinning, pre-harvest drop control and promotion of return bloom. Tomatoes, grapes, cherries and citrus account for a majority of the remaining uses. Several m a t e r i a l s have commercial use as a b s c i s s i o n agents (6). I n cotton, the products A c c e l e r a t e ( e n d o t h a l l ) , Folex (merphos) and DEF ( o x i d i z e d form o f merphos) have been i d e n t i f i e d as d e f o l i a n t s . Amid-thin continues to be used to t h i n f r u i t s e t . 3-CPA and Peach-thin 322, formerly used as peach t h i n n e r s , serve as reminders of the disadvantages o f h i g h l y s p e c i a l i z e d markets. RELEASE and PIK-OFF are under development as c i t r u s a b s c i s s i o n agents. Ethephon i s a recent example of a new generation p l a n t growth r e g u l a t o r . Among the r e g i s t e r e d uses, the a b s c i s s i o n o f c h e r r i e s has been o f major importance. The technology of u s i n g ethephon, grower i n t e r e s t and need, synchronized n i c e l y to 0-8412-0518-3/79/47-lll-281$05.00/0 © 1979 American Chemical Society

Mandava; Plant Growth Substances ACS Symposium Series; American Chemical Society: Washington, DC, 1979.


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provide a case where 95% of the c h e r r i e s i n Michigan are now harvested m e c h a n i c a l l y , A l s o l , another example of an ethylene r e l e a s e a b s c i s s i o n agent, has been u s e f u l i n the h a r v e s t i n g of o l i v e s . Growth r e g u l a t o r s , because of t h e i r r e l a t i v e l y high c o s t and methodological complexity have been u t i l i z e d i n h i g h - v a l u e s p e c i a l t y c r o p s . Most attempts to penetrate l a r g e r agronomic crops have been d i s a p p o i n t i n g . In recent y e a r s , companies have been d i r e c t i n g new r e s e a r c h towards p l a n t growth r e g u l a t o r s for l a r g e acreage crops such as: c o r n , wheat, soybeans, peanuts and c o t t o n (7). Although some p l a n t growth r e g u l a t o r s are commercially a v a i l a b l e many others of p o t e n t i a l value and those p r o v i d i n g measurable t e c h n i c a l success are n o t . Whether a p l a n t growth r e g u l a t o r , f o r example an a b s c i s s i o n agent, becomes a commercially a v a i l a b l e product depends on a v a r i e t y of i n t e r r e l a t e d s c i e n t i f i c and economic f a c t o r s . The s p e c i f i c c r i t e r i a used by p r i v a t e i n d u s t r y to evaluate a p o t e n t i a l new product i n c l u d e a d e s c r i p t i o n of product c h a r a c t e r i s t i c s and marketing f a c t o r s that c o r p o r a t i o n s must weigh before spending d o l l a r s to support a p r o j e c t . The o b j e c t i v e s of business are q u i t e c l e a r ; p r o f i t and market p o t e n t i a l must be considered because p r o f i t i s key to our economic system. For i n d u s t r y to engage i n the development and manufacture of a new p l a n t growth r é g u l a n t , an acceptable r e t u r n on investment must be assured. The u l t i m a t e c r i t e r i o n i s : "how many d o l l a r s w i l l be returned f o r an investment, how f a s t and w i t h i n what framework. T h i s must be the r e a l i n c e n t i v e f o r continued r e s e a r c h on any new product whether a new a b s c i s s i o n agent of any other p l a n t growth r e g u l a t o r . Thus unless there i s a good chance of adequate r e t u r n on investment to support the i n c r e a s i n g l y expensive business of a g r i c u l t u r a l chemicals R and D, a p l a n t growth r e g u l a t o r m a t e r i a l can be extremely r i s k y and subject to management d e l e t i o n . Over the past s e v e r a l y e a r s , we have i n c l u d e d w i t h i n the scope of a g r i c u l t u r a l R and D e f f o r t s the search f o r a b s c i s s i o n agents with prime emphasis on c i t r u s a b s c i s s i o n . My comments i n p a r t w i l l be drawn from f a c t o r s which have e f f e c t e d the development of the p o t e n t i a l a b s c i s s i o n agent RELEASE by Abbott Laboratories. Examples r e l a t i v e to the general concerns and o b s t a c l e s i n the development of a p l a n t growth r e g u l a t o r w i l l a l s o be d i s c u s s e d . 11

Scientific

Factors

Synthesis and Screening. One of the key problems f o r i n d u s t r y i s the question "How does one screen f o r new p l a n t growth r é g u l a n t s ? " (8). In the case of h e r b i c i d e s and i n s e c t i c i d e s , they e i t h e r work or they d o n ' t . The f i e l d e f f e c t s of p l a n t growth r e g u l a t o r s are harder to see, p r e d i c t or t e s t f o r .



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For the most p a r t , p l a n t growth r e g u l a t o r screening has been based upon n o n - s p e c i f i c general h e r b i c i d e screens where experience and i n t u i t i o n i n i n t e r p r e t i n g n o n - l e t h a l responses have been the main d r i v i n g f o r c e s l e a d i n g to f u r t h e r p l a n t growth t e s t i n g . Without a s e r i e s of d e t a i l e d t e s t s , i t i s e s s e n t i a l l y impossible to i d e n t i f y or p r e d i c t u s e f u l or commercial activity. The procedure of modifying a crop p r o p e r t y , such as enhancing y i e l d , i s much more d i f f i c u l t than k i l l i n g weeds or i n s e c t s . Inconsistency of r e s u l t s i s c h a r a c t e r i s t i c of p l a n t growth r e g u l a t o r s and a major problem i n t h e i r evaluation. I n i t i a l e f f o r t s aimed to i d e n t i f y a s p e c i f i c a c t i v i t y may, also , l e a d to a secondary response which may be u n a n t i c i p a t e d and e v e n t u a l l y more u s e f u l and economically important. Many p l a n t growth r e g u l a t o r s have been developed i n t h i s way a f t e r a c c i d e n t a l observations or v i a s e r e n d i p i t y . A l a r and ethephon are examples Ç 5 , 6 ) . In the case of c i t r u s a b s c i s s i o n , screening has i n v o l v e d s e v e r a l approaches: (9) 1. 2. 3.

Expiant t e s t s - l e a f and f r u i t Related whole p l a n t species - calamondin T r e e , limb t e s t i n g

In our experience, the expiant t e s t was h i g h l y v a r i a b l e and inconsistent. RELEASE would not have been found v i a t h i s r o u t e . The calamondin t e s t was u s e f u l i n developing data with good c a r r y - o v e r to f i e l d s c r e e n i n g . The c h e m i c a l - b i o l o g i c a l r e l a t i o n s h i p s developed by use of t h i s whole p l a n t had good agreement and o f f e r e d g u i d e l i n e s f o r the chemist to f o l l o w . As i l l u s t r a t e d ( F i g . 1 ) , s y n t h e s i s of r e l a t e d compounds to maximize a c t i v i t y (and i n c i d e n t a l b a l a n c i n g of p h y t o t o x i c i t y and p o t e n t i a l c o s t s ) can i n v o l v e the p r e p a r a t i o n of s e v e r a l hundred m a t e r i a l s - an expensive p r o p o s i t i o n . For p e s t i c i d e s g e n e r a l l y , only 1/200 compounds s u r v i v e s the i n i t i a l s y n t h e s i s and s c r e e n ing stage (10, 11, 12, 13). (There was no exception i n the case of RELEASE - r e l a t e d m a t e r i a l s ) . In expanded confirmatory t e s t s , questionable chemicals are c o n s t a n t l y d i s c a r d e d because o f narrow t o x i c i t y / e f f i c a c y r a t i o s or performance i s too e r r a t i c . Synthesis or formulation d i f f i c u l t i e s often compound t h i s picture. A s t e r l i n g example of i n d u s t r y and the research community cooperation i n developing s o p h i s t i c a t e d p l a n t growth r e g u l a t o r s i s the v e r y e n e r g e t i c c i t r u s a b s c i s s i o n screening program e s t a b l i s h e d by the Department of C i t r u s i n F l o r i d a . Support by i n d u s t r y growers, has made p o s s i b l e the screening of compounds at r a t e s of up to 9,000 compounds per y e a r . This p a r t n e r s h i p between growers and i n d u s t r y has allowed the screening and e v a l u a t i o n of approximately 50,000 compounds (9).


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I t i s one t h i n g to commit to a given d i s c o v e r y procedure once one f e e l s comfortable with the a b i l i t y to i n t e r p r e t or t r a n s l a t e a response to p o s s i b l e f i e l d a p p l i c a t i o n . I t i s a n other matter e n t i r e l y to "go a l l the way" i n development stages to prove e f f i c a c y and u t i l i t y ; human and environmental s a f e t y ; and acceptance by the farmer or grower. Many t e s t s are r e q u i r e d to have s a t i s f a c t i o n i n r e s u l t s obtained: e f f o r t s must i n c l u d e v a r i a t i o n i n r a t e s , t i m i n g , s p r a y , d i l u t i o n , formulation or tank mix c o m p a t i b i l i t i e s , v a r i e t a l responses, optimal environmental c o n d i t i o n s , geographical dependencies and season long and carry-over observations. The s i g n i f i c a n c e of l a b o r a t o r y or greenhouse screening data or d i f f i c u l t i e s i n t r a n s l a t i o n of these data can only be d e t e r mined a f t e r f i e l d e v a l u a t i o n s . A g a i n , i t must be r e a l i z e d that no amount of d e t a i l e d research under f i e l d c o n d i t i o n s can take i n t o account a l l the v a r i a b l e s encountered by a grower. G e n e r a l l y there has been a good t r a n s l a t i o n of r e s u l t s with RELEASE from i n i t i a l limb t e s t s to expanded whole tree e x p e r i ments but s t i l l not a l l v a r i a b l e s can be a n t i c i p a t e d . Thus i n f i e l d t e s t i n g of p l a n t growth r e g u l a t o r s , much needs to be learned but the investment of time and resources to develop a p e r f e c t product has been s e r i o u s l y questioned (8). Concurrent A c t i v i t i e s . While l a b o r a t o r y and f i e l d e v a l u a t i o n s are i n p r o g r e s s , s e v e r a l concurrent a c t i v i t i e s i n c l u d i n g patent p r e p a r a t i o n , chemical process development, p i l o t p l a n t and manufacturing estimates are i n v o l v e d and must be s e r i o u s l y addressed (10). The major a c t i v i t y or o b s t a c l e of concern i n developing and r e g i s t e r i n g a p l a n t growth r e g u l a t o r , or any p e s t i c i d e , i n v o l v e s the t o t a l t o x i c i t y and s a f e t y p r o f i l e . Of primary concern i s the impact of f e d e r a l agency r e g u l a t i o n s ; a t t e n t i o n i s g e n e r a l l y focused on the EPA (14, 15, 16, Γ 7 , 18). I t i s g e n e r a l l y conceded (or assumed) that s y n t h e t i c s , r a t h e r than the n a t u r a l l y o c c u r r i n g p l a n t growth r e g u l a t o r s , w i l l be developed f o r grower use. T h e r e f o r e , c l e a r understand ing of the impact of government r e g u l a t i o n s becomes of prime importance. F i r s t i t must be r e c o g n i z e d , d e s p i t e the s o p h i s t i cated nature and f u n c t i o n s of p l a n t growth r e g u l a t o r s , that they are i n f a c t p e s t i c i d e s and, t h e r e f o r e , subject to the requirements of FIFRA o r i g i n a l l y enacted i n 1947 and augmented i n 1972 by the F e d e r a l Environmental P e s t i c i d e C o n t r o l A c t (FEPCA) (8). Deadlines f o r completion of r e g i s t r a t i o n g u i d e l i n e s have been p r o g r e s s i v e l y extended with seemingly p e r p e t u a l new r e v i s i o n s . New p r o v i s i o n s have i n c l u d e d f i n a l implementation of FIFRA c e r t i f i c a t i o n of a p p l i c a t o r s ; r e - r e g i s t r a t i o n p r o c e dures f o r a l l products; c l a s s i f i c a t i o n of t o x i c i t y c a t e g o r i e s r e l a t i v e to RPAR - Rebuttable Presumptions Against R e g i s t r a t i o n .


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Before the amendments of FIFRA, the concept of n e g l i g i b l e residues was o p e r a t i v e . N e g l i g i b l e r e s i d u e s were g e n e r a l l y considered as any amount remaining which would r e s u l t i n a d a i l y intake regarded as t o x i c o l o g i c a l l y i n s i g n i f i c a n t on the b a s i s of s c i e n t i f i c judgment of adequate s a f e t y d a t a . O r d i n a r i l y t h i s would add an amount 1/2000 of the amount demonstrated to have no e f f e c t i n feeding studies on the most s e n s i t i v e animal s t u d i e d as shown by at l e a s t two (2) 90-day feeding s t u d i e s . C u r r e n t l y two-year c h r o n i c t o x i c i t y feeding s t u d i e s are r e q u i r e d for any p e s t i c i d e r e q u i r i n g a tolerance or exemption from the requirement of t o l e r a n c e . Safety and metabolism, c a r c i n o g e n i c i t y , t e r a t o g e n i c i t y , environmental and w i l d l i f e s t u d i e s are r e q u i r e d . In t o t a l , a s e r i e s of 30 or more t e s t s are necessary to meet the i n c r e a s i n g l y s t r i n g e n t requirements set out by the EPA. The end r e s u l t of these events i n c l u d e : (10, 11, 12, 13) (Fig. 2). 1.

Cost per new product have n e a r l y doubled s i n c e . . .

1970:

1967 - $ 3MM 1970 - $ 5MM 1978 - $10MM (Note: i n the l a s t year costs have r e p o r t e d l y increased $290,000 f o r registration alone),

2. Increase i n l e n g t h of time to product i n t r o d u c t i o n from an average of 60 months i n 1967 to 90-100 months. 3. Longer w a i t i n g p e r i o d s , decreasing the length of u s e f u l patent l i f e . 4. Cutbacks i n R and D spending, with r e d u c t i o n of spending f o r i n n o v a t i v e endeavors and increased emphasis on defensive or supportive r e s e a r c h on e x i s t i n g p r o d u c t s . Less i n t e r e s t r e s u l t s i n s p e c i a l - u s e m a t e r i a l s with p r i o r i t y assigned more to the major crop a r e a s . Perhaps one of the most p o l i t i c a l l y s e n s i t i v e areas i s that of o n c o g e n i c i t y . Many arguments on the q u a n t i t a t i o n of c a r c i n o g e n i c i t y have i n c l u d e d h i p - s h o o t i n g and emotional c o n t r o versy. I t i s s t i l l hoped that evidence of c a r c i n o g e n i c i t y w i l l not be the only step upon which r e g u l a t i o n s are based. Potency and r i s k of a c t u a l exposure from use p a t t e r n s w i l l h o p e f u l l y be c r i t i c a l l y considered. I f t h i s can be accomplished, b e t t e r d e l i n e a t i o n of impacts o f the r i s k and b e n e f i t s should r e s u l t (19). Economic F a c t o r s Determination of opportunity f o r any s p e c i f i c end-use p e s t i c i d e i s complex and can be demonstrated by s e v e r a l models which i l l u s t r a t e the major areas c r i t i c a l i n determining whether to cease or continue the p e s t i c i d e or p l a n t growth



Figure 2. Cost of commercial agricultural chemical and number of compou screened


P L A N T G R O W T H SUBSTANCES

288 regulator

development.

P r e l i m i n a r y Marketing P r o f i l e . Several preliminary questions must be answered before a market group can recommend f u r t h e r c a p i t a l investment. These i n c l u d e but are not l i m i t e d to: 1.

What i s the end-use spectrum r e l a t i v e to market opportunity? Is a t o t a l market p r o j e c t i o n p o s s i b l e ? What i s the competitive s i t u a t i o n ? What are the performance c h a r a c t e r i s t i c s of the p o t e n t i a l product?


2. "Fig.3" 3.

4. "Fig.4" 5.

What a r e the u n i t c o s t s r e l a t e d to end-use and production costs? Does the company have e x p e r t i s e or c a p a b i l i t i e s to serve markets?

E a r l y d e c i s i o n s based on q u a n t i f i c a t i o n of these questions are necessary to determine a l t e r n a t i v e steps or a GO, NO-GO decision (Fig. 5). As a new product candidate, RELEASE has not scored w e l l i n a p p r a i s a l of opportunity and investment demands to assure p r o b a b i l i t y of success f o r p o t e n t i a l marketing. As with any PGR m a t e r i a l , constant assessment i s necessary. P e s t i c i d e Opportunity P r o f i l e . In l o o k i n g at the t o t a l complex of R and D and marketing i n p u t s , there are a number of p o i n t s which must be understood to a n t i c i p a t e o b s t a c l e s or roadblocks which can impede or e l i m i n a t e f u r t h e r development (20). For example: (Fig. 6). 1. 2. 3.

*4. *5. *6. 7.

Underestimation of R and D and r e g i s t r a t i o n c o s t s . Lack of b a s i c knowledge of t o x i c i t y and mechanism of a c t i o n . Product s u p e r i o r i t y may be overestimated and may not represent a c t u a l grower need. New p r a c t i c e s or programs may r e q u i r e development for product acceptance by the grower ( 5 ) . Success i n the l a b o r a t o r y and the research p l o t i s one t h i n g - but u n l e s s someone buys the concept, a business venture can f a i l because estimates of c o s t - b e n e f i t s are not valid. A m u l t i - u s e product may be a n t i c i p a t e d , for ease of development, but other uses do not m a t e r i a l i z e . Inadequate market p o t e n t i a l (|

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Lack of support from a g r i c u l t u r a l researchers i n p u b l i c and p r i v a t e s e c t o r s ( i . e , product performance) (8). Overestimation of t r e a t a b l e acreage (5). v a r i e t a l use w i l l r e s t r i c t use of product s p e c i f i c geographical areas l i m i t product use Mechanical h a r v e s t i n g : . L e v e l s of technology and a v a i l a b i l i t y of t o t a l systems are not s u f f i c i e n t to be adapted by grower i n d u s t r y to allow p r e d i c t a b l e p e n e t r a t i o n i n a given c r o p . Weather v a r i a b l e s or requirements can e l i m i n a t e or reduce marketing o p p o r t u n i t i e s . . Ample labor s u p p l i e s delay i n t e r e s t and demands f o r mechanical h a r v e s t i n g a i d s presented.

The above l i s t of f a c t o r s i s not complete and i s not p r e sented to d i l u t e the o p p o r t u n i t i e s f o r s p e c i a l t y - u s e m a t e r i a l s but does provide r e a l i s t i c check p o i n t s of a n a l y s i s . * F a c t o r s A f f e c t i n g A b s c i s s i o n Agents Such as RELEASE . 1. L i m i t a t i o n to a s p e c i f i c c r o p ; e . g . , c i t r u s ; d i f f i c u l t y i n v a r i e t a l response ( V a l e n c i a ) . F a i l u r e to i d e n t i f y no m u l t i use p a t t e r n . 2. L i m i t e d market based on acreage expected e f f e c t i v e l y minor u s e s . P o t e n t i a l demand i s expected to mature to 300-400M acres "at some f u t u r e date" which i s d i f f i c u l t to d e f i n e . 3. Mechanical h a r v e s t i n g development has f l u c t u a t e d b e cause of a v a i l a b i l i t y of s u f f i c i e n t hand l a b o r . There i s d i f f i c u l t y i n e s t a b l i s h i n g b e n e f i t r a t i o s when need i s not c r i t i c a l f o r the use of the p l a n t growth r e g u l a t o r a i d i n mechanical harvesting. Future Of S p e c i a l t y - U s e Compounds The f u t u r e of s p e c i a l - u s e p l a n t growth r e g u l a t o r s (PGR) can be summarized thus: 1. P l a n t growth r e g u l a t o r s should be recognized as more than academic c u r i o s i t i e s . They are not only i n t e r e s t i n g but p r o f i t a b l e to use - to grower, d i s t r i b u t o r and manufacturer (21). 2. S t r i n g e n t r e g u l a t i o n s for r e g i s t r a t i o n w i l l continue to impact business ventures with PGR compounds. 3. Short-term o p p o r t u n i t i e s w i l l s t i l l be emphasized with a t t e n t i o n t u r n i n g to major f i e l d c r o p s . 4. We may s t i l l be i n the l a s t phases of PGR h i s t o r y where products i n the m i l l may s t i l l be ahead of t h e i r time i n terms of today's a p p l i c a t i o n s and recognized needs (5). 5. Because demands f o r food and heeds to i n c r e a s e land p r o d u c t i v i t y w i l l continue, hopes remain high f o r the p r a c t i c a l use of e x i s t i n g and new PGR chemicals under development (4).



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6. Industry w i l l remain c a u t i o u s l y o p t i m i s t i c and w i l l c o n s t a n t l y reassess the s i z e of investment demands and r i s k / b e n e f i t r a t i o s by addressing a multitude of questions on product n o v e l t y , performance, s a f e t y , R and D, r e g i s t r a t i o n , p r o d u c t i o n and marketing c o s t s and the u l t i m a t e r e t u r n on investment. It should be a p p r e c i a t e d , that i n d u s t r y w i l l not complain about investment requirements as_ long as a reasonable r e t u r n on i n vestment c o s t s can be achieved w i t h i n a reasonable length of time (8). 7. To maximize the chance of success, i t must not be assumed that the chemical i n d u s t r y alone can a f f o r d to bear the t o t a l burden (22, 23). I n d u s t r y , growers, grower companies, u n i v e r s i t i e s and extension must work together so that mutually supporting programs e v o l v e . Together we must recognize the o b l i g a t i o n s necessary to introduce products commensurate with needs of the grower/farmer, h i s a b i l i t y to understand and use the products c o r r e c t l y and the l i m i t s of commitment to assure r e g i s t r a t i o n of these p r o d u c t s . With such c o o p e r a t i o n , mutual support and o b v i o u s l y some "luck" (23), p l a n t growth r e g u l a t o r s , i n c l u d i n g a b s c i s s i o n agents, may s t i l l be expected to be developed (24, 25) not only to enhance q u a l i t y and y i e l d s of major crops; e . g . , c o t t o n , c o r n , tobacco, but a l s o important f r u i t crops; e . g . , a p p l e s , oranges ( c i t r u s ) , grapes, c h e r r i e s , e t c . REFERENCES

1.

Wittwer S. H., Bull. Plant Growth Regulator, 1974, 2,5.

2.

Chem. Wk., 1975, 116, (10), 41.

3.

Farm Chem., 1975, 138, (3), 15-25.

4.

Nickell L . G . , Chem. and Eng. News, 1978, 56, 18.

5.

Eggleton M.A., American Chemical Society Division of Chemical Economics and Marketing, National Meeting, 1977.

6.

Leidner J., Prog. Farm., 1977, (4), 44.

7.

Stanford Research Institute, 1973, Report 483.

8.

Mitlehner A.W., Bull. Plant Growth Regulator, 1974, 2,8.

9.

Wilson W.C. and Attaway J . A . , Bull. Plant Growth Regulator, 1974, 2, 18.

10. Farm Chem. 1964, 127, (5), 28. 11. Chem. & Eng. News, 1969,

47 (24) 22.


11.

CROVETTi


12. NACA Study 1971 - July. 13. Haschen T . L . , 1975. pp. 10-12. 14. Schwartz I, 1974.

Florist and Nurseryman, September 5, Chem. Wk., 114, (8), 31-36.

15. Farm Chem. 1975, 138, (3), 16. 16. Ouellette Robert P. and King John 1976, Chem. Wk., 118, (25), 27-38.


17. Arthur D. Little Impact Study, 1976. 18. Chem. and Eng. News, 1978, 56 (17),

15.

19. Chem and Eng. News, 1978, 56, (13), 3. 20. Blue Thomas A. Chemical Marketing and Economic Division of the American Chemical Society 1977, P.313-344. 21. Upchurch R.P.

Bull. Plant Growth Regulator 1974, 2, 20-22.

22. Holmsen T.W. Bull. Plant Growth Regulator 1976, 4, 2. 23. Upchurch R.P.

1976, ibid., 4, 4-5.

24. Tschabold Edward E., ibid. 1976, 4, 23. 25. Sharma M.P. Agriculture & Forestry Bulletin, 1977, Spring 27-32. RECEIVED

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19, 1979.


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