Pesticide Formulations - American Chemical Society

Chapter 11

Reduction of Pesticide Toxicity by Choices of Formulation J. L. Hudson and O. R. Tarwater

Downloaded by CORNELL UNIV on October 11, 2016 | http://pubs.acs.org Publication Date: June 24, 1988 | doi: 10.1021/bk-1988-0371.ch011

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285 While the t o x i c i t y of the active ingredient of a pesticide i s a property which cannot be changed, the acute t o x i c i t y e f f e c t s of the formulation (for example, dermal or ocular t o x i c i t y , or exposure of the mixer-loader) are strongly influenced by the way i n which the active ingredient i s formulated. Alternate formulation types often have d i f f e r e n t FIFRA ratings. An emulsifiable concentrate usually causes more severe ocular t o x i c i t y than does an aqueous suspension of the same active ingredient. The preliminary toxicology p r o f i l e of a new active ingredient can be u t i l i z e d i n deciding which formulation types to develop. For example, if a new active shows severe dermal irritation, the development of an emulsifiable concentrate should be avoided. Exposure of the mixer-loader i s strongly influenced by the formu l a t i o n type. While pesticide formulations are influenced by both the physical-chemical properties of the active ingredient and the economic pressures of the marketplace, there are formulation choices which will increase the safety of pesticide formulations.

The Formulation Science of Agrichemicals i s a challenging and s c i e n t i f i c a l l y rigorous research area that i s constrained by a) increasing economic pressures due to the general state of the farm economy; and b) governmental regulations that are designed to obtain the greatest safety p r o f i l e possible for our products. Safety concerns related to p e s t i c i d e products have been further highlighted by recent EPA actions including t h e i r p o l i c y on frequently used i n e r t ingredients i n pesticide products (Inert Ingredients i n Pesticide Products; P o l i c y Statement: Federal 0097-6156/88/0371-0124$06.00/0 ° 1988 American Chemical Society

Cross and Scher; Pesticide Formulations ACS Symposium Series; American Chemical Society: Washington, DC, 1988.


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Reduction of Pesticide Toxicity

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Register, A p r i l 22, 1987, Pages 13305-13309). Those i n e r t ingre dients of t o x i c o l o g i c a l concern should then be avoided for safety reasons. This then i s our challenge: develop e f f e c t i v e pesticide products that have high safety p r o f i l e s without substantially increasing the cost to the consumer. This research and develop ment must be done under rigorous s c i e n t i f i c standards. The formulation chemist's work i s further complicated by not having the luxury to select the active compounds with which new formulations must be developed. The choice of active ingredients i s usually the result of extensive laboratory and greenhouse screening as well as f i e l d research. Therefore, for the purpose of t h i s presentation the physical and chemical properties of the active ingredients w i l l not be considered. Comments r e l a t i v e to the choices of formulation ingredients w i l l be based on providing increased safety of the f i n a l product, usually to mixer-loader-applicators, as well as to chemists, formulators, processors, etc. Some attention w i l l be given to safety towards w i l d l i f e as well. Let us f i r s t spend a moment reviewing the general formu l a t i o n types, t h e i r inherent properties, and t h e i r market popularities. Sprayable

Formulations

Pesticide manufacturers produce more products of t h i s group than any other. This group includes emulsifiable concentrates (E.C.), aqueous suspensions (A.S.) or flowables (F), wettable powders (WP), water dispersible granules (WDG) or dry flowables (DF), and solutions (S). The physical and chemical properties of the active ingredient often dictate the type of formulation that may be p r a c t i c a l f o r a p a r t i c u l a r product. Liquid formulations have been desirable because they disperse well i n water and can be handled e a s i l y (pumping, measuring, e t c . ) . Emulsifiable concen trates and solutions have been p a r t i c u l a r l y well accepted because of t h e i r reduced agitation requirements after dispersion i n water. Aqueous suspensions also o f f e r some of these advantages, but may require more vigorous agitation for suspension than emulsifiable concentrates, p a r t i c u l a r l y a f t e r the mixture i s allowed to stand. S o l i d formulations such as wettable powders and dry flowables are also dispersed i n water before spraying. Obviously, a wettable powder i s capable of producing s i g n i f i c a n t amounts of dust, p a r t i c u l a r l y under windy conditions, and may present a concern to the mixer-loader. A well designed dry flowable i s e s s e n t i a l l y dust-free and has become increasingly more a t t r a c t i v e over the l a s t few years. Both of these formulation types have yielded products containing high concentrations of active ingre dient (80 to 90 percent) and can be economically a t t r a c t i v e . Nonsprayable Formulations These are products such as granules, dusts, briquettes, p e l l e t s , etc., which are applied d i r e c t l y without d i l u t i o n i n water.


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PESTICIDE FORMULATIONS: INNOVATIONS AND DEVELOPMENTS

Granules currently have major applications i n a v a r i e t y of market segments, while the other dry products are used f o r more specialized applications.


T o x i c i t y Considerations Throughout t h i s discussion, I w i l l be r e f e r r i n g to the rat acute o r a l t o x i c i t y , rabbit dermal t o x i c i t y and i r r i t a t i o n , rabbit ocular i r r i t a t i o n , and rat inhalation t o x i c i t y of various formu l a t i o n types based on t h e i r FIFRA categories, as outlined i n the Federal Insecticide, Fungicide, and Rodenticide Act (Labeling Requirements For Pesticides and Devices, Proposed Rule: Federal Register, September 26, 1984, Pages 37960-37995). I am sure that many of you are f a m i l i a r with this system, but I would l i k e to review i t b r i e f l y . Table I contains the types of hazard studies, FIFRA categories, and appropriate signal words for precautionary l a b e l l i n g statements on product labels.

Table I. FIFRA T o x i c i t y C r i t e r i a and Categories

Acute Hazard Studies Rat Oral LDso-mg/kg Rabbit Dermal LDso-mg/kg Rat Inhalation LC 4 hr exposure-mg/£ Rabbit Ocular Irritation

Category I 0-50

FIFRA Categories Category II Category III Category IV >50 - 500 >500 - 5000 >5000

0 - 200

>200 - 2000 >2000 - 5000 >5000

0 - 0.05

>0.05 - 0.5 >0.5

-5

>5

5 0

Irritation Corrosive or I r r i t a t i o n I r r i t a t i o n i r r e v e r s i b l e clearing i n clearing i n 21 days Mild or Rabbit Dermal Corrosive: Moderate Severe slight Irritation Tissue irritation irritation irritation at 72 hr destruction at 72 hr CAUTION Signal Word CAUTION DANGER WARNING Source: Labeling Requirements For Pesticides and Devices, Proposed Rule: Federal Register, September 26, 1984, Pages 37960-37995.

Products must be labeled with the signal word delineating the highest hazard of the various categories. A product with a high hazard category (FIFRA I, which carries a DANGER label) obviously presents increased hazards to the user and i n c e r t a i n cases may be regulated by EPA as a "Restricted Use Pesticide". As mentioned e a r l i e r , l i q u i d formulations, such as emulsi f i a b l e concentrates and aqueous suspensions (suspension concentrates or flowables), have been p a r t i c u l a r l y a t t r a c t i v e to the end user. However, emulsifiable concentrates generally are



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more i r r i t a t i n g to the eyes and skin than aqueous suspensions of the same active ingredient, probably because of the organic solvents and surfactants i n E.C. formulations. Experience with neat or undiluted solvents i s l i m i t e d , but heavy aromatic naphtha or xylene-range solvents are known to produce very s l i g h t eye i r r i t a t i o n . More polar solvents such as cyclohexanone or g l y c o l ethers have demonstrated moderate l e v e l s of ocular i r r i t a t i o n . Vegetable o i l s such as corn and soybean o i l s are reported to produce low orders of ocular i r r i t a t i o n . Unfortunately, they have not demonstrated the necessary solvency i n most cases to permit t h e i r economical use. Sometimes the safety of an E.C. may be increased either by decreasing the amount of emulsifier i n the system or by complete modification of the surfactant system. Emulsifiers normally are selected to give the best emulsion s t a b i l i t y i n a v a r i e t y of water hardnesses, temperatures, and perhaps i n l i q u i d f e r t i l i z e r s , but we have frequently observed that f i n e , stable emulsions produce more ocular i r r i t a t i o n than less elegant emulsions containing lower surfactant l e v e l s . The actual mechanism of increased ocular i r r i t a t i o n may be potentiation of the inherent t o x i c i t y of the active ingredient by increasing i t s surface area i n the smaller emulsified droplets, increased absorption due to an increase i n the l i p i d s o l u b i l i t y of the active ingredient, or disruption of l i p i d membrane b a r r i e r s i n the cornea. Emulsifier l e v e l s usually range from 3 to 5 percent, but i n c e r t a i n situations where additional f o l i a r wetting i s required, or where the properties of the active or solvent system d i c t a t e , higher l e v e l s may be used. These higher l e v e l s often r e s u l t i n severe dermal i r r i t a t i o n or corrosive ocular e f f e c t s , which i n turn r e s u l t i n FIFRA I c l a s s i f i c a t i o n s and DANGER product l a b e l s . Table II shows the r e s u l t i n g c l a s s i f i c a t i o n s for a p a r t i c u l a r fungicide i n various formulations. In these situations, formulation as an aqueous suspension (or flowable) rather than an E.C. may be the best choice.

Table I I .

FIFRA Hazard C l a s s i f i c a t i o n Comparisons of Various Fungicide Formulations

Formulation Type E.C. (1 lb/gal) E.C. (1 lb/gal) With Adjuvant A.S. (1 lb/gal) WP (12 percent)

Oral III III III III

FIFRA C l a s s i f i c a t i o n Dermal Ocular Inhalation I r r i t a t i o n Tox. III II Ill II III I III II IV IV

III III

III III

III III



128


When formulating aqueous suspensions, however, s i m i l a r "surprises" can occur. Several years ago we developed a "standard" flowable base f o r preparing small quantities of new actives to be evaluated by the plant s c i e n t i s t s . The formula contained t y p i c a l l i g n i n suspending agents, thickeners, an antifoam agent, and a wetting agent (either an alkylphenol ethoxylate or alkylether ethoxylate). A higher than normal l e v e l (10 percent) of the wetting agent was used to insure good wetting with possibly d i f f i c u l t actives, as well as to give the optimum spreading properties when the product was sprayed onto f o l i a g e . This water-based blank was tested f o r eye i r r i t a t i o n and resulted i n a FIFRA I rating. When the formula was revised to contain 5 percent surfactant, the rating dropped to FIFRA Category I I I . These, as well as many other surfactants, are known to have i r r i t a t i n g properties i n t h e i r concentrated state, but the degree of eye i r r i t a t i o n on d i l u t i o n to 10 percent was a surprise. Situations l i k e t h i s demonstrate the need to select surfactants with low i r r i t a t i o n properties. Most surfactant manufacturers publish the acute t o x i c o l o g i c a l properties of t h e i r products, and these can be of value i n surfactant selection. Increased Safety of Liquid

Formulations

There are other possible ways to increase the safety of l i q u i d formulations. Increasing the Concentration of Active Ingredient i n an E.C. I f the s o l u b i l i t y properties of the solvent system w i l l allow, a higher concentration of active may result i n lower i r r i t a t i o n properties. This would indicate greater i r r i t a n c y of the emulsifier/solvent system than of the active ingredient. Microencapsulation of the Active. There are products on the market i n which the microencapsulated formulation i s less hazardous than the conventional formulation. This i s p a r t i c u l a r l y true i f the active i t s e l f has high inherent t o x i c i t y . The encapsulation of methyl parathion i n PENNCAP-M i s an example of the successful use of t h i s process. Concentrated Emulsions (CE). These are pre-emulsified concen trates where part of the solvent i s replaced with water. Our experience with a herbicide CE formulation has demonstrated reduced eye i r r i t a t i o n when compared to a conventional E.C. of the same concentration, (FIFRA III versus FIFRA I I ) . Of course, i t may also be appropriate to consider replacing the l i q u i d formula with a dry form that can be applied through spray equipment. Sprayable s o l i d formulations generally include wettable powders (WP) and water dispersible granules or dry flowables (WDG or DF). During the past few years we have seen the development of a v a r i e t y of WDG's, i n some cases supple menting or replacing a WP of the same active. Wettable powders are dusty when handled and may present a concern to the mixerloader. However, unless the active i t s e l f has inherent toxic



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properties, the WP may demonstrate safe levels of inhalation t o x i c i t y . We have also seen the replacement of WP products with aqueous suspensions. This has been achieved i n cases where the active has low s o l u b i l i t y i n water and i s chemically stable i n a water-based v e h i c l e . A dry flowable formulation should be as hard and a t t r i t i o n free as possible to reduce the formation of dust during shipping and handling. The hardness or d u r a b i l i t y properties must be balanced against the need f o r good dispersion properties i n water. Packaging of dry flowables i s usually important and should consist of f a i r l y r i g i d containers with the package as f u l l as possible to reduce a t t r i t i o n of the product. Nonsprayable formulations such as granules, p e l l e t s , and briquettes should be as dust-free and resistant to a t t r i t i o n as possible. In the development of a granular product, the use of a harder LVM clay rather than the softer RVM clay c a r r i e r may be of value. The use of high-boiling l i q u i d s such as mineral o i l to bind the dust may be h e l p f u l . Dust may also be minimized i n a granular product by selecting the correct p a r t i c l e - s i z e range where fines are e l i m i nated by screening. This can usually be accomplished by selecting specifications with the supplier. As with dry flowables, attention to correct packaging w i l l minimize product a t t r i t i o n and dust formation. Other forms of granular c a r r i e r s are c e r t a i n l y possible. Clay c a r r i e r s are most frequently used because of t h e i r low cost, but other c a r r i e r materials can be developed to provide variations i n release of the active, p a r t i c u l a r l y i f a conven t i o n a l clay granule demonstrates excessive human, avian, or even phytotoxicity. Granule c a r r i e r s such as the starch matrix developed by the USDA, ARS i n Peoria, may find applications to improve the safety of granular products. Elanco Products has developed a series of d i f f e r e n t types of formulations f o r the same active ingredient. In Table III the respective FIFRA categories f o r the E . C , the powder concen t r a t e , the DF, and the granule are presented. I t i s obvious from t h i s example that the ocular i r r i t a t i o n can be very d i f f e r e n t f o r d i f f e r e n t formulations of the same active ingredient, and that changes i n the other t o x i c i t y categories may also occur. Table I I I . Comparison of Different Formulation Types f o r the Same Active Ingredient

Formulation Type Oral E.C. No. 1 III (1.5 lb/gal) E.C. No. 2 III (1.5 lb/gal) DF (60 percent) III IV 2.5 G (30/60 mesh) Powder Concentrate IV (50 percent)

FIFRA Categories Dermal I r r i t a t i o n Tox. Ocular I IV III

Inhalation III

III

IV

II

III

III IV IV

IV IV IV

III III III

III IV IV


130


Packaging Packaging concepts also o f f e r some useful opportunities with wettable powders. These products can be packaged i n watersoluble f i l m packets which may be d i r e c t l y added to the spray tank, thereby avoiding exposure to the operators. The user exposure data presented i n Table IV demonstrate the difference i n contact to the mixer-loader and the applicator when using a conventional 50 WP and one i n a water-soluble packet.


Table IV. Mixer/Loader/Applicator Exposure Data f o r an Experimental 50W - Plant Growth Regulator

Route of Exposure Inhalation, ug/lb a . i . Dermal, mg/lb a . i .

Package Type Conventional Bag Water Soluble Packet 3.8 0.47 2A 0.041

Water-soluble packets may also have u t i l i t y i n reducing exposure to products formulated as E.C. s. A few years ago we investigated the compatibility of an E.C. formulation with conventional p o l y v i n y l alcohol films. The product showed good compatibility with the f i l m and could be f i l l e d i n pouches of up to at least eight ounces. The only problem was the a b i l i t y to completely avoid leakage, the l i q u i d s being more successful than a powder i n finding an imperfect seal. The results were encour aging, however, and I believe the concept could be developed f o r an E.C. that may have i r r i t a t i n g properties. 1

Acute Hazard of Granules to W i l d l i f e Avian t o x i c i t y from granules may be minimized by selecting the correct p a r t i c l e - s i z e range and using a low concentration of active ingredient. Studies have indicated that p a r t i c l e s below 30-mesh are infrequently selected by b i r d s . I f the active ingredient concentration i s low, the b i r d may be repelled by the p a r t i c l e rather than developing a toxic response. Highly colored granules should also be avoided. In general, the safety of a granule w i l l be increased i f the granule blends i n with the s o i l . The suggestions presented here f o r improvements i n product safety w i l l not present solutions to a l l of our situations. At the same time I hope that some of the ideas w i l l be helpful i n our formulation e f f o r t s , and that less hazardous product formu lations can be produced. RECEIVED December 28,1987


Pesticide Formulations - American Chemical Society

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