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Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on March 20, 2018 | https://pubs.acs.org Publication Date: February 25, 1985 | doi: 10.1021/bk-1985-0273.ch032

Risk Assessment of Excess Pesticide Exposure to Workers in California Κ. T. MADDY, R. G. WANG, JAMES B. KNAAK, C. L. LIAO, S. C. EDMISTON, and C. K. WINTER Worker Health and Safety Unit, California Department of Food and Agriculture, Sacramento, CA 95814 Pesticides are selected because they have specific adverse biological effects on certain organisms. Unfortunately, many pesticides are also toxic to humans and beneficial organisms. The pesticide safety program of the California Department of Food and Agriculture involves evaluation of measurements of: (1) amounts of pesticide vapors, mists, or dusts in the breathing zone of persons who may be exposed; (2) amounts of pesticide dusts, powders, or liquids that reach the skin of persons applying pesticides; (3) levels of pesticide residues, including the more toxic breakdown products on foliage and soil of fields and other places where work is to take place subsequent to appli cation; (4) urine excretion rates; and/or, (5) any biologic adverse effects in exposed persons. In order to better evaluate human exposure risk, the following data may be required of registrants either before or after registra tion: (1) indoor exposure data; (2) mixer, loader, and applicator exposure data; (3) dislodgeble leaf residue and soil residue data; and, (4) dermal absorption rate data. In the past, little of this type of information was avail able nor was it supplied by pesticide registrants. Separate studies to monitor exposure levels of pesticides in the workplace are being conducted by CDFA for certain pesticides currently registered. These measurements are of value in designing methods to keep user exposures at low levels and to determine if adequate safety margins exist to protect against identified or suspected adverse health effects. The E n v i r o n m e n t a l P r o t e c t i o n Agency (EPA), when f i r s t created i n 1970, continued the approach of i t s predecessor, the United States Department of Agriculture (USDA), i n evaluating the o v e r a l l t o x i c i t y of a p a r t i c u l a r chemical. In assigning signal words, which suggest the p o t e n t i a l hazard, the USDA and then the EPA emphasized acute t o x i c i t y , often f o c u s i n g on the hazard of a c c i d e n t a l i n g e s t i o n . They did not place a high p r i o r i t y on evaluating workplace exposure. 0097-6156/85/0273-0445$06.00/0 © 1985 American Chemical Society

Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985.


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In 1971, new C a l i f o r n i a laws began t o emphasize r e q u i r e m e n t s f o r assessing t o t a l workplace hazards f o r p e s t i c i d e users ( i n c l u d i n g l o n g - t e r m e x p o s u r e h a z a r d s ) and ways o f m i t i g a t i n g t h e s e h a z a r d s . T h i s has r e s u l t e d i n s p e c i f i c C a l i f o r n i a r e q u i r e m e n t s f o r d a t a w h i c h may be used t o e s t i m a t e such hazards. D u r i n g t h e EPA's R e b u t t a b l e P r e s u m p t i o n A g a i n s t R e g i s t r a t i o n (RPAR) p r o c e s s (now c a l l e d S p e c i a l Review), i t became apparent t h a t i f uses o f c e r t a i n p e s t i c i d e s w i t h i d e n t i f i e d p o t e n t i a l s f o r c a u s i n g a d v e r s e e f f e c t s w e r e t o be c o n t i n u e d , u s e r e x p o s u r e d a t a w o u l d be needed t h a t demonstrated m i n i m a l exposure hazards when c e r t a i n use p r o c e d u r e s were f o l l o w e d . S c i e n t i s t s o f both the EPA and the S c i e n t i f i c A d v i s o r y P a n e l (SAP) t o EPA t h e n r e a l i z e d t h a t t h e y c o u l d n o t make s a t i s f a c t o r y r i s k assessments and e v a l u a t e the impact o f c o n t i nued use w i t h o u t a c t u a l w o r k p l a c e exposure data. C a l i f o r n i a Program The p e s t i c i d e worker s a f e t y program o f t h e C a l i f o r n i a Department o f Food a n d A g r i c u l t u r e (CDFA) i n c l u d e s t h e c o n s i d e r a t i o n o f : 1) amounts o f p e s t i c i d e v a p o r s , m i s t s , o r d u s t s i n t h e b r e a t h i n g zone of e x p o s e d p e r s o n s ; 2) amounts o f p e s t i c i d e d u s t s , p o w d e r s o r l i q u i d s on t h e s k i n o f p e r s o n s m i x i n g , l o a d i n g , a n d / o r a p p l y i n g p e s t i c i d e s ; 3) l e v e l s o f p e s t i c i d e r e s i d u e s , i n c l u d i n g t h e more t o x i c breakdown p r o d u c t s , on f o l i a g e and s o i l o f f i e l d s where work i s t o t a k e p l a c e subsequent t o a p p l i c a t i o n w h i c h may l a t e r c o n t a c t s k i n ; 4) r e s i d u e s i n t h e a i r , o n f l o o r s , c o u n t e r s , e t c . , f o l l o w i n g a p p l i c a t i o n o f p e s t i c i d e s i n d o o r s t h a t may be i n h a l e d o r be c o n t a c t e d by s k i n . I n t h e p a s t , l i t t l e o f t h i s t y p e o f i n f o r m a t i o n was a v a i l a b l e ; nor was i t s u p p l i e d by p e s t i c i d e r e g i s t r a n t s . S t u d i e s o f worker exposure l e v e l s i n t h e w o r k p l a c e a r e conducted by t h e CDFA for c e r t a i n p e s t i c i d e s c u r r e n t l y r e g i s t e r e d . A l s o i n C a l i f o r n i a , these k i n d s o f data are c u r r e n t l y r e q u i r e d o f the r e g i s t r a n t s p r i o r to r e g i s t r a t i o n o f c e r t a i n p e s t i c i d e s , p a r t i c u l a r l y those w i t h h i g h a c u t e o r subacute t o x i c i t y o r a p o t e n t i a l t o produce c e r t a i n c h r o n i c effects. These measurements a r e o f v a l u e i n d e s i g n i n g methods t o reduce e x p o s u r e o f a l l p e r s o n s , i n c l u d i n g p e r s o n s who u s e p e s t i c i d e s i n a p a r t m e n t s , h o u s e s , a n d y a r d s . CDFA e v a l u a t e s b a s i c t o x i c o l o g y d a t a , e x p o s u r e m e a s u r e m e n t s a n d t h e manner i n w h i c h t h e p e s t i c i d e p r o d u c t i s t o be u s e d . By m o d i f y i n g t h e way t h e p e s t i c i d e i s t o be used, e s t a b l i s h i n g r e e n t r y i n t e r v a l s , o r s u g g e s t i n g changes t o EPA of p r e c a u t i o n a r y statements on p e s t i c i d e l a b e l s , t h e r i s k o f expos u r e t o a p o t e n t i a l l y h a z a r d o u s p e s t i c i d e may be g r e a t l y r e d u c e d . The CDFA g a t h e r s a n d a n a l y z e s d e t a i l e d i n f o r m a t i o n on more t h a n 2,000 i l l n e s s r e p o r t s per year from p h y s i c i a n s who d e s c r i b e p o s s i b l e o c c u p a t i o n a l exposures t o s p e c i f i c p e s t i c i d e s , as w e l l as more than 12,000 i n q u i r i e s h a n d l e d each year by p o i s o n i n f o r m a t i o n c e n t e r s i n C a l i f o r n i a on n o n - o c c u p a t i o n a l exposures. T h i s i n f o r m a t i o n i s used to a s s i s t i n d e v e l o p i n g t r a i n i n g programs, d e v e l o p i n g worker s a f e t y r e g u l a t i o n s , and i n e v a l u a t i n g proposed r e g i s t r a t i o n s , i n an e f f o r t to m i n i m i z e e x p o s u r e s . I n o r d e r t o c o m p l e t e t h e r i s k a s s e s s m e n t p r o c e s s , t h e CDFA a l s o e x a m i n e s e x p o s u r e d a t a g e n e r a t e d by r e g i s trants.



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A major d i f f i c u l t y i n making hazard assessments for any persons who might be exposed before, during, and after a pesticide a p p l i c a tion i s the lack of information on the amount of pesticide that may be inhaled or may reach the skin, the extent of dermal absorption, the rate and pathway of biotransformation, and the route of eliminat i o n from the body. The f o l l o w i n g are some of the data that may be required by CDFA to a s s i s t i n making exposure estimates of persons i n v o l v e d i n various a c t i v i t i e s i n v o l v i n g the use of pesticides: indoor exposure; f i e l d reentry; mixer, loader, and applicator exposure, dermal absorption, and dermal dose response data. Indoor Exposure. Products to be used indoors (houses, i n s t i t u t i o n s , greenhouses, etc.), may have p o t e n t i a l exposure ( i n h a l a t i o n , dermal, and ingestion) hazards both during the a p p l i c a t i o n and upon reentry. An appropriate v e n t i l a t i o n period may be needed to protect residents, inhabitants, or workers i n the treated area from i n h a l a t i o n of hazardous chemicals as w e l l as from contacting residues on carpets, countertops, etc. A study o u t l i n e has been developed and used by the CDFA f o r s t u d i e s i t conducts to a c q u i r e needed data; t h i s i s a v a i l a b l e upon request f o r o t h e r s to use to p l a n t h e i r studies. F i e l d Reentry. Certain pesticides pose a potential hazard to f i e l d workers i f they enter a t r e a t e d area and have s i g n i f i c a n t contact with t r e a t e d p l a n t s or s o i l (JL.). C u r r e n t l y , CDFA p l a c e s major emphasis on exposure to the f o l i a g e of c i t r u s , grapes, peaches, nectarines, and apples. EPA now also has guidelines for developing f i e l d worker reentry data. The f o l l o w i n g i s a guide suggested and used by CDFA i n deciding i f reentry data i s needed. Such data may be needed i f the product i s to be a p p l i e d to a commercially grown crop, p a r t i c u l a r l y to i t s f o l i a g e or the s o i l , and c u l t u r a l p r a c t i c e s (such as pruning or h a r v e s t i n g ) of t h a t p a r t i c u l a r crop i n v o l v i n g substantial body contact with the f o l i a g e , bark, or s o i l , or exposure to p e s t i c i d e r e s i d u e s shaken from the f o l i a g e or bark, and the product c o n t a i n s : (a) a c h o l i n e s t e r a s e i n h i b i t o r ; or (b) a s i g n i f i c a n t l y toxic p r i n c i p l e that can cause a detrimental acute systemic toxic reaction or i s suspected of causing a c h r o n i c e f f e c t , and may be r e a d i l y absorbed through the s k i n or i n h a l e d f o l l o w i n g exposure to p e s t i c i d e residues contacted while conducting usual c u l t u r a l practices; or_ (c) a chemical which causes a s i g n i f i c a n t primary s k i n i r r i t a n t r e a c t i o n i n a p p r o p r i a t e t e s t animals or man; or (d) a chemical which i s a s i g n i f i c a n t skin sensit i z e r i n appropriate test animals or man. Reentry i n t e r v a l s are now e s t a b l i s h e d on the b a s i s of: ( 1 ) data on dermal absorption or dermal dose response; (2) inhalation, dermal, and o r a l acute t o x i c i t y studies i n animal models; (3) f o l i a r and s o i l residue d i s s i p a t i o n data; and, (4) a v a i l a b l e human exposure data. CDFA recommends s e v e r a l sources as useful guides for determ i n i n g r e s i d u e s of p e s t i c i d e s on s o i l and l e a f s u r f a c e s ( d i s l o d g e a b l e r e s i d u e ) and conducting f i e l d r e e n t r y s t u d i e s i n v o l v i n g human volunteers (1-5). Human exposure studies may not be r e q u i r e d i f adequate animal data from (1) through (3) above are available.

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Mixer. Loader. Applicator Exposure. In order to make an appropriate hazard assessment, information i s needed on the amount of pesticide that may be inhaled, and/or reach the skin and more importantly the amount being absorbed during a " t y p i c a l " application. A study outl i n e i s a v a i l a b l e from CDFA. It places emphasis as f o l l o w s : Testing should be performed using the formulated product to be marketed, and used i n accordance w i t h the proposed l a b e l . I t i s preferable for the applications being studied to be at the maximum rate specified and the least d i l u t i o n permitted i n the use instructions. The period of exposure studied should be on at least three different workdays i n which s u f f i c i e n t work i s accomplished during each day to allow the investigators to c o l l e c t meaningful and representative samples; a minimum of four hours of work per day i s d e s i r able. S u f f i c i e n t numbers of workers should be monitored during the study to gather meaningful and representative data. Reported values s h o u l d i n c l u d e data from at l e a s t f o u r d i f f e r e n t workers i f possible. The workers should be employees who are routinely engaged i n the mixing/loading or a p p l i c a t i o n of pesticides. Informed consent and a p p r o p r i a t e human s u b j e c t s review may be r e q u i r e d f o r studies done i n C a l i f o r n i a i f the pesticide or the use of the p e s t i cide being studied does not have Federal Experimental, Federal or C a l i f o r n i a Conditional, or f u l l C a l i f o r n i a registration. Exposure should be as r e a l i s t i c as p o s s i b l e . Only the p r o t e c t i v e items proposed or already required on existing or proposed l a b e l i n g — f o r example, protective clothing such as long-sleeved cotton c o v e r a l l s , and protective equipment such as impervious gloves and impervious foot c o v e r i n g — a r e to be worn. If additional protection i s specif i e d on the l a b e l or proposed l a b e l , i t should be c a r e f u l l y complied with i n the study. Toxicity Category I l i q u i d pesticides should be transferred from their o r i g i n a l containers to mixing or a p p l i c a t i o n tanks through closed transfer systems. Exposures of persons should not be conducted with e x c e s s i v e l y dusty t o x i c i t y Category I p e s t i c i d e s u n t i l d u s t i n e s s i s reduced to a l e v e l a c c e p t a b l e f o r use i n C a l i f o r n i a . (A summary of a number of s t u d i e s conducted i n C a l i f o r n i a by CDFA i s included i n Appendix One.) Dermal Absorption and Dermal Dose-Response. These data are needed i n the r i s k assessment of f i e l d workers, mixers/loaders, applicators, and f l a g g e r s ; they may a l s o be used i n the development of r e e n t r y i n t e r v a l s . The data gathered informs CDFA of how much of the chemic a l a c t u a l l y enters the body once i t comes i n t o contact w i t h the skin. Guides for these types of studies i n test animals are a v a i l able through, and were conducted by, the CDFA. At times, data from human volunteer studies are a v a i l a b l e ; when a v a i l a b l e , t h i s type of information u s u a l l y takes precedence over animal test data. Hazard Evaluation (Risk Assessment) The CDFA, i n i t s hazard e v a l u a t i o n process, determines whether an adequate hazard assessment can be made immediately, or i f additional data are needed, based on the c o n s i d e r a t i o n of the f o l l o w i n g factors: 1.

Review of the basic toxicology data submitted by the registrant;


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Review o f o t h e r t o x i c o l o g y d a t a a v a i l a b l e t o t h e U n i t ( j o u r n a l a r t i c l e s , u n i t s t u d i e s , computerized n a t i o n a l d a t a banks, t e x t s , etc.) ; Human i l l n e s s i n f o r m a t i o n d e v e l o p e d by t h e u n i t o r o t h e r s i n v o l v i n g t h e p e s t i c i d e under c o n s i d e r a t i o n o r s i m i l a r p e s t i c i d e s ; A v a i l a b l e e x p o s u r e d a t a on t h i s p e s t i c i d e o r t h i s c l a s s o f p e s t i c i d e s d e v e l o p e d by t h i s u n i t o r any o t h e r group; and, Work p r a c t i c e s known a b o u t o r e x p e c t e d i n C a l i f o r n i a f o r t h e proposed u s e .

The CDFA d e v e l o p s and c o n t i n u e s t o u p d a t e d a t a on p e s t i c i d e r e l a t e d i l l n e s s e s f o r s p e c i f i c p e s t i c i d e s as t o when, why, and how they o c c u r . The U n i t a l s o measures how much exposure o c c u r s i n t h e wide v a r i e t y o f use s i t u a t i o n s . The b a s i c t o x i c o l o g y r e v i e w i n f o r m s t h e D e p a r t m e n t o f t h e e x t e n t and adequacy o f t h e d a t a base upon which t h e e v a l u a t i o n o f a p o t e n t i a l use h a z a r d i s t o be made. A h a z a r d e v a l u a t i o n d i f f e r s c o n s i d e r a b l y from a b a s i c t o x i c o l o g y r e v i e w . F o r example, a s p e c i f i c p e s t i c i d e can be found i n t h e t o x i c o l o g y r e v i e w t o be e x t r e m e l y t o x i c . H o w e v e r , i n t h e h a z a r d e v a l u a t i o n p r o c e s s , i t may be determined t h a t t h e product i s to be used i n such s m a l l q u a n t i t i e s w i t h s p e c i a l i z e d equipment t h a t a person c o u l d o n l y be overexposed i n t h e u n u s u a l case o f equipment f a i l u r e . On t h e o t h e r h a n d , a p r o d u c t c o u l d be f o u n d t o be o f l o w t o x i c i t y ; b u t , t h e most common use might i n v o l v e l o n g hours o f exposure t o many workers i n o r c h a r d s w h i l e u s i n g h a n d - h e l d spray wands ( s p r a y i n g t h e p e s t i c i d e a b o v e t h e i r h e a d s ) w i t h no p r o t e c t i v e c l o t h i n g due t o l a c k o f s p e c i f i c a t i o n i n t h e p r e c a u t i o n a r y label statements. I n another example, t h e b a s i c t o x i c o l o g y data f o r a product may o n l y i n d i c a t e a moderate t o x i c i t y ; however, i n a s s e s s i n g the proposed use o f t h e p r o d u c t mid-summer i n a c i t r u s g r o v e i n t h e San J o a q u i n V a l l e y , t h e r e c o u l d be s u b s t a n t i a l c o n v e r s i o n o f t h e a c t i v e i n g r e d i e n t t o a h i g h l y t o x i c dégradâtive product under a c t u a l f i e l d c o n d i t i o n s w h i c h w o u l d be hazardous t o f i e l d workers. O f t e n t h e d a t a s u b m i t t e d by t h e r e g i s t r a n t t o meet EPA r e q u i r e ments i s a l s o adequate f o r t h e CDFA t o complete a h a z a r d e v a l u a t i o n , e s p e c i a l l y f o r many o f t h e l o w t o x i c i t y a n d l o w h a z a r d p r o d u c t s . The CDFA may r e q u i r e a d d i t i o n a l d a t a , a s d i s c u s s e d a b o v e , t o comp l e t e the hazard e v a l u a t i o n . The 1. 2. 3.

4. 5. 6.

CDFA r e v i e w may i n c l u d e : D e t e r m i n i n g t h e use p a t t e r n o f t h e proposed p r o d u c t ; D e t e r m i n i n g s i g n i f i c a n t human exposure h a z a r d s ; E v a l u a t i n g t h e adequacy o f use i n s t r u c t i o n s and/or r e g u l a t i o n s t h a t a r e i n p l a c e t o i n f o r m users o f the p o s s i b l e use hazards and how t o a v o i d excess exposure. E v a l u a t i n g t h e adequacy o f i n f o r m a t i o n p r o v i d e d t o r e c o g n i z e i l l n e s s due t o exposure i f i t o c c u r s ; D e t e r m i n i n g t h e adequacy o f f i r s t a i d i n f o r m a t i o n ; and, Examining t h e a v a i l a b i l i t y o f d a t a t o support m e d i c a l management.

Data from t h e t o x i c o l o g y base, p l u s those from t h e a d d i t i o n a l H e a l t h and S a f e t y s t u d i e s t h a t a r e sometimes r e q u i r e d , a l l o w f o r t h e



450


estimation and c a l c u l a t i o n of potential exposure hazards. For some products, experience already gained allows for a quick determination that adherence to the use instructions should r e s u l t i n a low hazard situation. On the other hand, a small percentage of the pesticides considered f o r r e g i s t r a t i o n have s i g n i f i c a n t hazards from either a short-term or long-term exposure standpoint. These hazards are estimated and/or c a l c u l a t e d to determine i f a favorable recommendat i o n on the proposed r e g i s t r a t i o n can be given and, i f not, whether additional r e s t r i c t i o n s would be expected to acceptably reduce the hazards of use. For example, a p a r t i c u l a r product might be a h i g h l y dusty wettable powder with only moderate acute t o x i c i t y but with demonstrated potential for producing chronic effects. The c a l c u l a t i o n s for the hazard evaluation are based upon the t o t a l workday measurement of the skin and i n h a l a t i o n exposure to this pesticide when i t i s used i n accord with the l a b e l instructions. This potential d a i l y dose i s then adjusted by the estimated 24-hour dermal absorption rate. This f i n a l figure i s compared to animal test data for the dose expected to produce a s p e c i f i c adverse e f f e c t . The s a f e t y f a c t o r f o r t h i s s p e c i f i c effect w i l l then be c a l c u l a t e d to determine i f i t i s adequate to p r o t e c t the workers. In some cases, r e s u l t s of c a l c u l a tions might not give an acceptable safety factor f o r a mixer/loader; but, i f this product were packaged i n water-soluble packets or i f i t were to be used as a l i q u i d product and r e q u i r e d to be t r a n s f e r r e d through a closed system, the hazard might be acceptably reduced. Of p a r t i c u l a r concern are p o t e n t i a l adverse e f f e c t s such as carcinogenicity, f e t o t o x i c i t y , and teratogenicity. The f o l l o w i n g i s given to i l l u s t r a t e the assessment process by CDFA of these types of adverse health e f f e c t s . Cancer Risk Assessment. Based on chronic animal bioassay and mutagenicity testing r e s u l t s , an in-depth review i s conducted to determine whether the product i s an animal carcinogen. I f p o s i t i v e r e s u l t s have been confirmed, the chemical undergoes further evaluat i o n . The p o s s i b l e mode of a c t i o n i s then determined to be: (1) a genotoxin (exhibited p o s i t i v e r e s u l t s i n a chronic animal bioassay i n at least one animal species tested, i n conjunction with a battery of p o s i t i v e mutagenicity tests); or, (2) an epigenetic toxin (minimal or weakly p o s i t i v e r e s u l t s i n a c h r o n i c animal bioassay and a battery of negative mutagenicity tests). A ranking system (modified Squire) (6j_ 7) i s then used which takes into consideration a v a r i e t y of v i t a l parameters; such as number, species and sex of animals a f f e c t e d , tumor type, organs i n v o l v e d , malignancy and r a r i t y of tumor, tumor incidence i n comparison to the incidence of spontaneous tumors, dose range and dose response, and the r e s u l t s of a b a t t e r y of mutagenicity tests. Then, from the worker exposure data, an average and a maximum exposure l e v e l for each type of work a c t i v i t y i n v o l v e d with p e s t i cide use i s taken into consideration. The number of workers i n each job category, the t o t a l y e a r l y body dose (which may be derived from number of hours/days/months exposure i n performing the job), and the t o t a l dermal absorption i s a l l taken into consideration. Residue l e v e l s (including degradation products) found i n treated crops or a p a r t i c u l a r product are used to assess consumer risk.


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AL.

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451

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A cancer r i s k assessment i s made u s i n g the c u r r e n t l y a v a i l a b l e m a t h e m a t i c a l m o d e l s , as suggested by the EPA. (See Appendix Two f o r an example of a CDFA assessment of c a r c i nogenic r i s k . ) F e t o t o x i c i t y and T e r a t o g e n i c i t y R i s k Assessment. The CDFA has devel o p e d a g u i d e l i n e f o r e v a l u a t i n g f e t o t o x i c i t y and t e r a t o g e n i c i t y (8). A number of v i t a l parameters are c o n s i d e r e d i n t h i s r a n k i n g of teratogens. T h e s e i n c l u d e , but a r e n o t l i m i t e d t o , t h e n a t u r e o f major and minor m a l f o r m a t i o n s , m a t e r n a l t o x i c i t y and l e t h a l i t y , a t w h i c h dosages m o r p h o l o g i c a l changes of the embryoes and f e t u s e s are b e i n g o b s e r v e d , e f f e c t i v e d o s e r a n g e , and maximum no o b s e r v a b l e e f f e c t l e v e l (NOEL), and the r o u t e of a d m i n i s t r a t i o n . S i n c e f e t o t o x i c and t e r a t o g e n i c responses d i f f e r q u a l i t a t i v e l y , so does t h e " p o t e n c y " o f an e m b r y o t o x i n o r a t e r a t o g e n . CDFA d i f ferentiates b e t w e e n h i g h d o s e and l o w d o s e t e r a t o g e n s ; for instance, a chemical which exerts a f e t o t o x i c / t e r a t o g e n i c e f f e c t w i t h a d o s e as l i t t l e as 0.1 mg/kg/day when g i v e n d u r i n g o r g a n o g e n e s i s i s n o t a b l y more p o t e n t t h a n another product w h i c h does not e x e r t a f e t o t o x i c / t e r a t o g e n i c response u n t i l a dose of 300 mg/kg/day i s g i v e n . The r a n k i n g t h a t a f e t o t o x i n / t e r a t o g e n r e c e i v e s d e t e r mines the a c c e p t a b l e s a f e t y f a c t o r needed to m i t i g a t e the h e a l t h h a z a r d d u r i n g e x p o s u r e . The t o t a l body d o s e (mg/kg/day) a c t u a l l y a b s o r b e d by t h e w o r k e r d u r i n g a t y p i c a l w o r k d a y d i v i d e d by a n i m a l NOEL (mg/kg/day) r e p r e s e n t s the s a f e t y f a c t o r t h a t i s o b t a i n e d f o r t h a t p a r t i c u l a r work a c t i v i t y . T h i s i s t h e n compared t o the accept a b l e s a f e t y f a c t o r . From t h i s , i t i s determined whether adequate safety i s reasonably achievable. I n s u c h c a s e s when t h e r e i s an inadequate s a f e t y f a c t o r , a d d i t i o n a l m i t i g a t i o n measures are t a k e n t o e n s u r e a d e q u a t e w o r k e r p r o t e c t i o n i f r e g i s t r a t i o n i s t o be g r a n t e d o'r m a i n t a i n e d . Safety Factors. The f o l l o w i n g i s CDFA's c u r r e n t g u i d e l i n e f o r safety f a c t o r s required to m i t i g a t e v a r i o u s t o x i c o l o g i c a l e f f e c t s . I f the d e s i r e d s a f e t y f a c t o r cannot be a c h i e v e d , use of t h a t product i s i n q u e s t i o n , u n l e s s a d d i t i o n a l p r a c t i c e s to i n c r e a s e s a f e t y can be a p p l i e d s u c h as use o f c l o s e d s y s t e m t r a n s f e r , w a t e r - s o l u b l e packaging, s p e c i f y i n g l e s s h a z a r d o u s work p r a c t i c e s , or r e q u i r i n g special protective clothing. For each of the f o l l o w i n g e f f e c t s , a minimum s a f e t y f a c t o r i s a p p l i e d t o t h e No O b s e r v a b l e E f f e c t L e v e l (NOEL) i n t e s t a n i m a l s . I n a c u t e a n i m a l exposure s t u d i e s , the maximum dose l e v e l which p r o duces no d e t e c t a b l e c l i n i c a l i l l n e s s e s , no b i o c h e m i c a l changes, no h i s t o p a t h o l o g i c a l c h a n g e s and no d e a t h s i s c o n s i d e r e d t o be t h e NOEL. Adverse E f f e c t s 1.

2.

Acute E f f e c t s a. C h o l i n e s t e r a s e i n h i b i t i o n b. Other a c u t e e f f e c t s

Safety

Factors

10-fold 20-fold

E f f e c t s on R e p r o d u c t i o n


452


a.


3. 4.

General reproduction ( i n c l u d i n g reductions i n (1) number o f o f f - s p r i n g , (2) f e r t i l i t y , (3) sperm c o u n t s , and (4) s i z e o f t e s t e s , etc.) 50 f o l d b. E m b r y o t o x i c / f e t o t o x i c e f f e c t s 50 f o l d c. T e r a t o g e n i c e f f e c t s 50 t o 300 f o l d Delayed-Oneet N e u r o t o x i c E f f e c t s 50 f o l d Oncogenicity (including mutagenicity) Risk Assessments *

*The l i f e t i m e r i s k o f c a n c e r i s u s u a l l y c a l c u l a t e d by u s i n g one o f t h r e e m o d e l s : (1) t h e o n e - h i t m o d e l (9^. 1 0 ) ; (2) t h e m u l t i - s t a g e model (11. 12); and, (3) a c h o i c e o f a t h i r d model u s u a l l y t h e W e i b e l model o r t h e improved M a n t e l - B r y a n model (13, 14). The r i s k c a l c u l a t i o n s a r e made by comparing t h e dose response c u r v e o b t a i n e d from a n i m a l exposures t o t h e human exposure data. a.

F o r consumers o f treated crops

b.

For f i e l d

c.

For mixers, applicators

workers

loaders,

Not more than one a d d i t i o n a l e s t i mated case o f cancer i n t h e l i f e t i m e o f 1,000,000 persons. Not more t h a n one a d d i t i o n a l e s t i mated case o f c a n c e r i n t h e l i f e t i m e o f 300,000 persons. Not more t h a n one a d d i t i o n a l e s t i mated case o f c a n c e r i n t h e l i f e t i m e o f 100,000 persons. F o r a few y e a r s , a r i s k as h i g h as 1 i n 10,000 may be t o l e r a t e d i n t h e case o f extreme need.

Adequacy o f M i t i g a t i o n Measures A f t e r a l l r e l e v a n t data are e v a l u a t e d , an assessment i s made as t o t h e adequacy o f t h e ' p o s s i b l e m i t i g a t i o n m e a s u r e s t o p r o t e c t w o r k e r s f r o m h a z a r d s o f u s e . The p r o d u c t l a b e l may be a c c e p t e d a n d t h e p r o d u c t may be r e g i s t e r e d without f u r t h e r concern. On t h e o t h e r h a n d , o n e o r more o f t h e f o l l o w i n g c o n d i t i o n s may be r e q u i r e d b e f o r e t h e product i s c o n s i d e r e d f o r r e g i s t r a t i o n by t h e CDFA: (1) t h e EPA may be a d v i s e d o f t h e d e s i r a b i l i t y o f r e q u i r i n g a l a b e l change, o r the r e g i s t r a n t may r e c o g n i z e t h e n e e d t o a s k EPA f o r a l a b e l c h a n g e ; (2) a C a l i f o r n i a r e g u l a t i o n o n t h e u s e may be e n a c t e d ( w h i c h w i l l h a v e t h e same e f f e c t a s a l a b e l c h a n g e , b u t t h i s c a n t a k e a number o f m o n t h s t o a c c o m p l i s h ) ; (3) t h e p r o d u c t may be made a C a l i f o r n i a r e s t r i c t e d m a t e r i a l which w i l l a l l o w i m p o s i t i o n o f s p e c i f i c permit requirements ( t h i s p r o c e s s c a n a l s o t a k e a number o f m o n t h s ) ; (4) c l o s e d s y s t e m t r a n s f e r o f l i q u i d p e s t i c i d e s may be r e q u i r e d , ( t h i s i s c u r r e n t l y r e q u i r e d f o r a l l t o x i c i t y C a t e g o r y I l i q u i d s , when s p e c i f i e d o n l a b e l s r e g a r d l e s s o f t h e t o x i c i t y c a t e g o r y and when s p e c i f i c a l l y r e q u i r e d by r e g u l a t i o n s ) ; (5) change i n t h e p r o d u c t ' s f o r m u l a t i o n may be r e q u i r e d t o r e d u c e e x c e s s h a z a r d s (e.g., r e d u c e d u s t i n e s s ) ; (6) w a t e r - s o l u b l e p a c k a g i n g o f t h e more t o x i c p o w d e r s may be r e q u i r e d ; (7) minimum f i e l d r e e n t r y i n t e r v a l s may be s e t by r e g u l a t i o n (a s e v e r a l - m o n t h p r o c e s s u n l e s s t h e y a r e a d e q u a t e l y s p e c i f i e d on t h e l a b e l ) ; (8) m e d i c a l s u p e r v i s i o n may be r e q u i r e d by r e g u l a t i o n ; and/or (9) d e t a i l e d s a f e t y t r a i n i n g may be r e q u i r e d f o r s p e c i f i c pesticides.


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I f h a z a r d s o f u s e c a n n o t be m i t i g a t e d by means t h a t c a n be r e a s o n a b l y employed, the product w i l l not be r e g i s t e r e d .


CONCLUSIONS E x c e s s i v e unnecessary warnings on e v e r y use o f e v e r y product c o u l d l e a d to workers t a k i n g a c a s u a l a t t i t u d e i n t h e i r use of a l l p r o ducts. On the o t h e r hand, t h e r e has been so much s c r u t i n y and c o n c e r n about t h e use o f p e s t i c i d e s i n r e c e n t y e a r s t h a t i t i s i m p o r t a n t t o w a r n o f r e a l h a z a r d s and t o b a s e i n f o r m a t i o n on how t o reduce exposure t o p e s t i c i d e s on t h e best p o s s i b l e t e c h n i c a l i n f o r m a t i o n . T h i s i n f o r m a t i o n c l e a r l y s t a t e d on the product i s o f bene fit to: (1) t h e manufacturer who has spent m i l l i o n s o f d o l l a r s i n d e v e l o p i n g a p r o d u c t and who wishes t o s e l l a n d / o r c o n t i n u e t o s e l l i t ; (2) t h e u s e r s who may c o l l e c t i v e l y r e c e i v e f i n a n c i a l b e n e f i t s or a more c o m f o r t a b l e p e s t - f r e e s i t u a t i o n f r o m t h e p r o p e r u s e o f t h e p r o d u c t ; (3) t h e person who h a n d l e s t h e p e s t i c i d e , s i n c e he i s t o l d e x a c t l y what t h e use hazards a r e and how t o a v o i d them; as w e l l a s , (4) t h e many members o f t h e g e n e r a l p u b l i c who h a v e c o n c e r n s t h a t p e s t i c i d e s a r e n o t b e i n g used c a r e f u l l y enough.

Literature Cited 1. Knaak, J.B.; Schlocker, P.; Ackerman, C.R.; and, Seiber, J.N. Bull. Environ. Contam. Toxicol. 1980, 24. 2. Iwata, Y.; Knaak, J.B.; Spear, R.C.; and, Foster, R.J. Bull. Environ. Contam. Toxicol. 1977. 18. 649. 3. Spencer, W. F.; Iwata, Y.; Kilgore, W.N.; and, Knaak, J.B. B u l l . Environ. Contam. Toxicol.1977. 18. 656. 4. Iwata, Y.; Knaak, J.B.; Carman, G.E.; Dusch, M.E.; and, Gunther, F.A. Journal of Agricultural and Food Chemistry 1982, 30, 215. 5. Kahn, E. Residue Reviews 1979, 70, 27. 6. Squire, R.A. Science 1981, 214. 877. 7. Wang, R.G. 1984, In-House Document, Worker Health and Safety Unit. State of California. 8. Wang, R.G. 1984, In-House Document, Worker Health and Safety Unit. State of California. 9. Armitage, P. J. Nat'l. Cancer Inst. 1959, 23, 1313. 10. Crump, K.S.; Guess, H.A.; and, Deal, K.L. Biometrics 1977, 33, 437. 11. Van Ryzin, J . ; and, R a i , K. In H.R. Witschi (ed.), Elvesier/North Holland Biomedical Press 1980, 273-290. 12. Crump, K.S. Biometrics 1979, 35, 157. 13. Armitage, P. Biometrics (Supplement) 1982, 38, 119-129. 14. Mantel, N.; Bohidar, N.R.; Brown, C.C.; Ciminera, J.L.; and, Tukey, J.W. Cane. Res. 1975, 35., 865.


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Appendix One: Dermal Exposure M o n i t o r i n g o f M i x e r s , L o a d e r s , and A p p l i c a t o r s o f P e s t i c i d e s i n C a l i f o r n i a

Some p e s t i c i d e s p o s s e s s t h e p o t e n t i a l t o c a u s e a d v e r s e h e a l t h e f f e c t s i n workers who are exposed to these c h e m i c a l s d u r i n g the application process (1-3). Concerns about these h e a l t h h a z a r d s have l e d to the development o f e x p o s u r e m o n i t o r i n g techniques designed to h e l p u n d e r s t a n d the f a c t o r s i n f l u e n c i n g pesticide exposure. Data generated from these t e c h n i q u e s a s s i s t i n the development o f p r e v e n t i v e measures i n c l u d i n g the use o f p r o t e c t i v e c l o t h i n g and e q u i p m e n t , m e d i c a l s u p e r v i s i o n o f e m p l o y e e s , increased awareness o f the need for proper personal hygiene practices, improved label statements and government r e g u l a t i o n s . E a r l y attempts at m o n i t o r i n g worker exposure to p e s t i c i d e s d u r i n g a p p l i c a t i o n were performed by B a t c h e l o r and Walker (4) and Durham and W o l f e (5^). T h e y m e a s u r e d d e r m a l e x p o s u r e by p l a c i n g s m a l l f i l t e r pads on the s k i n o f the workers i n a r e a s not p r o t e c t e d by c l o t h i n g . A n a l y s i s o f the c o l l e c t e d r e s i d u e s and e x t r a p o l a t i o n o f the r e s u l t s to the e n t i r e u n p r o t e c t e d s u r f a c e a r e a gave r i s e t o an e s t i m a t e d t o t a l dermal e x p o s u r e . P o t e n t i a l i n h a l a t i o n exposure was a l s o monitored by a n a l y z i n g r e s p i r a t o r pads o f f a c e masks f o r pesticide residue. R e s u l t s i n d i c a t e d that dermal exposure to p e s t i c i d e s b e i n g a p p l i e d o u t d o o r s t o f o l i a g e was by f a r , o f g r e a t e r c o n c e r n than i n h a l a t i o n exposure d u r i n g a p p l i c a t i o n f o r i t s p o t e n t i a l to cause a c u t e h e a l t h e f f e c t s . These r e s u l t s a r e c o n s i s t e n t w i t h those o b t a i n e d from o t h e r s t u d i e s ( 6 - 8 ) . Durham and Wolfe (5) assumed t h a t workers i n v o l v e d i n p e s t i c i d e a p p l i c a t i o n s u s u a l l y wore shoes, socks, long t r o u s e r s , a s h o r t s l e e v e d open-necked s h i r t , but no h a t , r e s p i r a t o r , o r g l o v e s . They reasoned t h a t the m a j o r i t y o f the dermal exposure o f the workers w o u l d o c c u r on t h e u n p r o t e c t e d s k i n a r e a s o f t h e f a c e , h a n d s , forearms, back o f neck, f r o n t o f neck, and the "V" o f the c h e s t . Exposure to o t h e r a r e a s i s p r o t e c t e d by c l o t h i n g , a l t h o u g h some p e n e t r a t i o n may s t i l l occur (9-11). The c a p a c i t y t o p e n e t r a t e c l o t h i n g depends on the i n d i v i d u a l c h e m i c a l , as w e l l as i t s f o r m u l a t i o n , the amount used, and the s p e c i f i c f a b r i c used i n the c l o t h i n g . C a l i f o r n i a r e g u l a t i o n s r e q u i r e d a i l y p r o v i s i o n and use o f c l e a n c o v e r a l l s o r o t h e r c l e a n o u t e r c l o t h i n g to m i x e r s , l o a d e r s , f l a g g e r s , and a p p l i c a t o r s o f any p e s t i c i d e i n t o x i c i t y C a t e g o r i e s I and I I (12). These r e q u i r e m e n t s s e r v e to reduce the p o t e n t i a l dermal exposure o f workers to p e s t i c i d e s by d e c r e a s i n g the a r e a o f b a r e s k i n a v a i l a b l e f o r c o n t a c t w i t h the c h e m i c a l s . The C a l i f o r n i a Department o f Food and A g r i c u l t u r e (CDFA) has attempted to e s t i m a t e p e s t i c i d e exposure o f body a r e a s p r o t e c t e d by clothing. T h i s r e p o r t summarizes e x p e r i m e n t a l s t u d i e s which attempt to e s t i m a t e t o t a l dermal exposure and the d i f f e r e n t amounts o f t h i s exposure which o c c u r on v a r i o u s p a r t s o f the body.


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California

455


Methods CDFA conducted dermal exposure monitoring of workers involved in the application of parathion, mevinphos (Phosdrin), n i t r o f e n (TOK), DEF/Folex, and chlorobenzilate (Acaraben) ( 1 3 - 1 8 ) . Exposures of mixers/loaders, ground applicators, mixers/loaders/ground applicators (workers performing a l l three a c t i v i t i e s during a single applicat i o n ) , a e r i a l applicators, and flaggers were determined in a t o t a l of 102 individual exposure situations. In a l l the exposure situations, workers wore cloth coveralls. Rubber or some other type of waterproof gloves were worn by a l l workers except the a e r i a l applicators and flaggers. Respirators and other protective devices were used when required by pesticide labels. Hand exposure was determined by r i n s i n g the hands i n a predetermined s o l v e n t c o n t a i n i n g e i t h e r water, soap and water, ethanol, or a combination of the three. Hands were rinsed prior to and upon completion of the applications. Wettable and soluble powders are usually well removed with soap and water; for other formulations, solvents such as ethanol often were more e f f i c i e n t . Exposures to the head, face, and neck were estimated by placing small cloth pads on the upper c o l l a r of the coveralls i n the front and back, or, i n some cases, placing smaller pads d i r e c t l y on the face. Amounts of chemicals in these pads were extrapolated to the entire surface areas of these body parts. Potential exposure to skin p r o t e c t e d by cotton coveralls was measured with pads measuring 49 cm made of an outer l a y e r o f seven-ounce 65 percent dacron polyester, 35 percent cotton t w i l l , and an inner layer of 100 percent cotton gauze backed by aluminum foil. The p e s t i c i d e found on the gauze p o r t i o n was assumed to simulate the amount which would penetrate the coverall material and reach the skin. The composition of the outer pad was c o n s i s t e n t with most commercially available c o v e r a l l s . As i n the case of the head, face, and neck exposures, values were extrapolated to estimate exposures of the t o t a l surface area. Results Tables I, II, and III summarize the average percentage of total dermal exposure found on various regions by individual chemical and job a c t i v i t y , respectively. The hands are not considered to be a protected area, as such, even though waterproof gloves were usually worn. Table IV summarizes the amounts of p e s t i c i d e that were estimated to have reached the skin. Discussion The results presented in the Tables show that estimated exposure to p r o t e c t e d body areas r e p r e s e n t e d , on the average, 23.3 percent of the t o t a l dermal exposure. S t a t i s t i c a l analysis u t i l i z i n g one-way analysis of variance was performed to determine whether the average percentage of t o t a l dermal exposure found on the unprotected areas



456


d i f f e r e d by chemical or job a c t i v i t y . Calculated F-values of 1.84 and 1.21, respectively, were below the value of 2.49 required for s t a t i s t i c a l significance at the p=0.05 l e v e l . It was concluded, that the average contribution of the unprotected areas to the t o t a l dermal exposure did not appear to strongly depend upon the chemical or job a c t i v i t y involved in the situations monitored by CDFA. The f a c t that hand exposure exceeded exposure to a l l other areas was not surprising; other studies have shown similar results (10, 11, 19) even when gloves were worn. Workers who wore waterproof gloves s t i l l experienced hand exposures, representing 40.9 percent of their t o t a l dermal exposure. Possible explanations for the r e l a t i v e ineffectiveness of the gloves include: (1) contamination of the inside material of the gloves; (2) removal of gloves during mechanical adjustments to the application equipment; and, (3) the handling of the outside of contaminated gloves while putting them on or taking them o f f . This does not imply that the wearing of gloves would be expected to increase exposure to pesticides; the data merely suggests that the potential for waterproof gloves to prevent exposure of the hands i s not routinely maximized. Quantitative data for actual penetration of glove materials by s p e c i f i c chemicals i s often not available to CDFA, but there i s some evidence that this i s only a minor factor i n contamination of the hands. Questions arise as to the necessity of monitoring protected areas i f only 23.3 percent of the t o t a l dermal exposure occurs i n these areas. A q u a l i t a t i v e study of worker exposure using fluorescent tracers led to the conclusion that "results depend c r i t i c a l l y on knowing where to place the pads" (11) . This study also demonstrated that the principal exposure was to the face, hands, and neck. In some studies, p a r t i c u l a r l y screening studies, more attention should be given to the monitoring of the hands, head, face, and neck, and less attention to monitoring protected areas. The a b i l i t y of a chemical to penetrate protective clothing and, thus, present hazards to protected skin areas, could be quantitated in the laboratory prior to the commencement of a f i e l d study i n order to determine whether sampling protected areas might be necessary. Current techniques in hand monitoring could be improved by performing additional handwashes and calculating the extraction e f f i c i e n c i e s of the various solvents used (19). Thin cloth gloves can be used as inserts in the usually-worn waterproof gloves to be e x t r a c t e d p e r i o d i c a l l y to estimate the amount of chemical which reaches the skin. Direct methods for face and neck monitoring, such as swabbing (6) or skin washing (20), are p o s s i b i l i t i e s for improving accuracy over the current pad exposure techniques. These techniques would place less emphasis on extrapolâtive methods, and would also enable i d e n t i f i c a tion of the protective c a p a b i l i t i e s of faceshields, goggles, and respirators i n the reduction of dermal exposure. The actual b i o l o g i c a l monitoring of workers to detect evidence of exposure such as a drop i n blood cholinesterase levels or the presence of a urinary metabolite i s superior to the indirect techniques employed i n t h i s study. R e a l i z i n g the d i f f i c u l t i e s i n accurately determining the dermal exposures of mixers, loaders, and applicators to pesticides, the employment of simpler monitoring techniques than the ones performed by CDFA i n this report might



s t u d i e s as r e f e r e n c e d

25% WP EC 25% EC 24%, WP 50% 70% EC 45% EC

F o r m u l a t i o n Type

f o r more d e t a i l s .

A i r Blast-Ground Airplane/Helicopter Boom-Ground Airplane O s c i l l a t i n g Boom/Hand wands

Parathion Mevinphos TOK DEF/Folex Chlorbenzilate

See s p e c i f i c

A p p l i c a t i o n Type

Chemical

Acres Treated P e r Hour 4 50 t o 12 175 2

Pounds Per A c r e of Active Ingredient 2.5 0.5 t o 1 3.5 1.5 2.2 t o 2.7

T a b l e I . P e s t i c i d e s Used i n 102 D i f f e r e n t A p p l i c a t i o n s t o Farm F i e l d s i n C a l i f o r n i a D u r i n g Which Exposure o f Workers I n v o l v e d i n t h e A p p l i c a t i o n s Were M o n i t o r e d



Chemical Mixer/Loader, Ground Applicator Mixer/Loader Aerial Applicator Ground Applicator Flagger Total

Chemical Parathion Mevinphos TOK DEF/Folex Chlorobenzilate Total

4 36 18 25 19 102

Number of Exposures Monitored

Number of Exposures Monitored 3 22 24 32 21 102

18.1 50.7 54.6 30.4 38.7 42.9

t o T o t a l Dermal

57.5 22.0 27.4 47.9 38.6 33.8

Average Percentage on Head, Face, and Neck

75.6 72.7 82.0 78.3 77.3 76.7

Average Percentage on Hands and Head, Face, and Neck

Exposure

Average Percentage on Hands and Head, Face, and Neck 90.8 82.6 71.9 70.5 86.5 76.7

of Body Areas by Job A c t i v i t y

Contributions

Average Percentage on Head, Face, and Neck 67.4 34.6 22.7 23.7 59.4 33.8

Relative

Average Percentage on Hands

Table I I I .

Average Percentage on Hands 23.4 48.0 49.2 46.8 27.1 42.9

Table I I . Relative Contributions to Total Dermal Exposure of Body Areas to Pesticides as Studied by the C a l i f o r n i a Department of Food and Agriculture

24.4 27.3 18.0 21.7 22.7 23.3

Average Percentage on Protected Areas

Average Percentage on Protected Areas 9.2 17.4 28.1 29.5 13.5 23.3


Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985. 1.837

091.787

1.400

2.641

0.767

0.866

Mixer/Loader Only

A e r i a l Applicator

Ground Applicator Only

Flagger For Airplane

078.910

08.400

015.960

0.09791.787

0.148 19.106

1.030

0.850

0.200

1.662

6.168

0.634

023.072

0.03020.650

03.989

012.950

1.71373.396

0.08720.650

0.05323.072

0.0234.9896

0-1.691

0.953

0.606

1.663

0.425

3.653

0.262

2.139

0.707

0

Ο ΙΟ.241

07513.000

02.629

024.516

1.9406.736

07688.000

0.40324.516

0-3.967

0-6.951

Protected Areas Median Range 3.042 1.9406.736

5.111

3.5

6.027

5.853

14.803

12.775

10.240

5.285

Range 14.22699.238

029.389

0.1757523.425

017.733

0.29994.500

6.63 99.238

0.1757523.425

4.08740.190

0.25929.883

0-8.856

Total

0.254

Median 15.380

— Studies were based on 102 use s i t u a t i o n s . Amounts are expressed i n milligrams of active ingredient that reached the s k i n . Absorption rates are not given.

6.145

Activity Mixer/Loader, Ground Applicator

.96

0.29317.270

4.626

De f/Fol ex

Chlorobenzilate

1.811

0.14825.255

0.943

0.028

TOK

0-3.383

0.081

Phosdrin

Head, Face, & Neck Median Range 7.332 5.00373.396

Median 7.335

Hands Range 4.954 19.106

E s t i m a t e d Dermal Exposure o f Workers t o P e s t i c i d e s A d j u s t e d f o r a Seven-Hour Work P e r i o d as S t u d i e d by the C a l i f o r n i a Department o f Food and A g r i c u l t u r e - /

Mg/Day Chemical Parathion

T a b l e IV.


D E R M A L E X P O S U R E R E L A T E D TO PESTICIDE U S E


460

y i e l d useful results p a r t i c u l a r l y for p i l o t studies or range-finding studies. For example, since hand exposure was, on the average, responsible for more than 42 percent of the t o t a l dermal exposure, estimates of t o t a l dermal exposure could be derived by multiplying the hand exposure by a factor of 2.5. This rough estimate should be accurate within one order of magnitude and, as such, would generally enable adequate determination of potential health risks for regula tory purposes. Caution should be exercised in comparing the dermal exposure values found in these studies with other studies. These dermal exposure levels are as much as one-tenth of the amount found for other similar applications of similar pesticides outside of C a l i fornia. A l l persons were working in accord with C a l i f o r n i a Worker Safety and Restricted Materials Regulations and a l l applications were made by trained employees of C a l i f o r n i a Pest Control Operators. A l l of these formulations studied were C a l i f o r n i a Restricted P e s t i cides and almost a l l were t o x i c i t y Category I liquids which are required to be mixed and loaded through closed systems. A l l workers put on clean outer clothes d a i l y and a l l wore impervious gloves when contact with the concentrate was a p o s s i b i l i t y . On the other hand, caution was exercised to avoid special t r a i n i n g , extra instructions or excessive observation because the employers and employees had been instructed to apply the pesticides in the usual manner.

References 1. Kay, K. L.; Monkman, L.; Windish, J. P.; Doherty, T.; Pare', J.; and Racicot. C.A.M.A. Arch. Indust. Hyg. 1952, 6, 252. 2. Sumerford, W. T.; Hayes, W. J . ; Johnston, J. M.; Walker, K.; and Spillane, J. A.M.A. Arch. Indust. Hyg. 1953. 3. Jegier, Z.: Health Hazards in Insecticide Spraying of Crops. Arch. Environ. Health 1964, 8, 670. 4. Batchelor, G. S. and Walker, K. C. A.M.A. Arch. Indust. Hyg., 1954, 10, 522. 5. Durham, W. F. and Wolfe, H. R. Bull WHO 1962, 26, 75. 6. Durham, W. F. Arch. Environ. Health 1965, 10, 842. 7. Hartwell, W. V.; Hayes, G. R.; and Funckes, A. J. Arch. Environ. Health 1964, 8, 820. 8. Durham, W. F.; Wolfe, H. R.; and Elliott, J. W. Arch. Environ. Health 1972, 24, 381. 9. Davies, J. E.; Freed, V. H.; Enos, H. F.; Duncan, R. C.; Barquet, Α.; Morgade, C.; Peters, L. J . ; and Danauskas, J. X. J. Occup. Med. 1982, 24, 464. 10. Leavitt, J. R.; Gold, R. E.; Holcslaw, T.; and Tupy, D. Arch. Environ. Contam. Toxicol. 1982, 11, 57. 11. Franklin, C. Α.; Fenske, R. Α.; Greenhalgh, R.; Mathieu, L.; Denley, H. V.; Leffingwell, J. T.; and Spear, R. C. J . Toxicol. Environ. Health 1981, 7_, 715. 12. California Administrative Code, Title 3, Sect. 2477 (h) , Sacramento, California. 13. Maddy, K. T.; Winter, C. K.; Saini, N.; and Quan, V. HS-888, Worker Health and Safety Unit 1982. State of California. 14. Maddy, K. T.; Winter, C.; Cepello, S.; and Fredrickson, A. S. HS-876, Worker Health and Safety Unit 1981. State of Cali fornia. Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985.

32.

15. 16.


17. 18. 19. 20.

M A D D Y ET

AL.

Excess Pesticide Exposure to Workers in California

461

Maddy, K. T.; Winter, C.; Cepello, S.; and Fredrickson, A. S. HS-889, Worker Health and Safety Unit 1982. State of California. Maddy, K. T.; O'Connell, L. P.; Winter, C. K.; and Margetich, S. HS-903, Worker Health and Safety Unit 1982. State of California. Maddy, K. T.; Johnston, L.; Smith, C.; Schneider, F.; and Jackson, T. HS-745 Worker Health and Safety Unit 1980. State of California. Peoples, S. Α.; Maddy, K. T.; Datta, P. R.; Johnston, L.; Smith, C.; Conrad, D.; and Cooper, C. HS-676, Worker Health and Safety Unit 1981. State of California. Davis, J. E. Residue Reviews 1980, 75, 34. Keenan, R. R. and Cole, S. B. Am. Ind. Hyg. Assoc. J. 1982, 43, 473.


D E R M A L E X P O S U R E R E L A T E D TO PESTICIDE USE

462

Appendix Two: Cancer R i s k Assessment f o r Persons I n v o l v e d i n A p p l i c a t i o n o f Chlordimeform as a P e s t i c i d e to Cotton F i e l d s i n C a l i f o r n i a


Summary C h l o r d i m e f o r m i s used as a p e s t i c i d e on c o t t o n f i e l d s i n two count i e s i n C a l i f o r n i a under a c l o s e l y r e g u l a t e d worker exposure c o n t r o l program. Animal t e s t data i n d i c a t e s that t h i s chemical i s a c a r c i nogen. U r i n a r y m e t a b o l i t e s ( a n i l i n e d e r i v a t i v e s ) of t h i s c h e m i c a l w e r e m e a s u r e d i n w o r k e r s who w e r e i n v o l v e d i n t h i s a p p l i c a t i o n . These v a l u e s were used i n e s t i m a t i n g cancer r i s k o f exposed workers. I t was d e t e r m i n e d t h a t w i t h v e r y c l o s e a t t e n t i o n t o m i m i m i z i n g i n h a l a t i o n and dermal exposure t o t h i s c h e m i c a l , i f exposure were l i m i t e d t o f i v e d a y s a week, 10 weeks a y e a r , f o r o n l y 10 y e a r s , c a n c e r r i s k m i g h t be k e p t as l o w as one c h a n c e i n 500,000 o f an e x t r a case of cancer i n the l i f e t i m e o f such an exposed person. On t h e o t h e r hand, i f o n l y average a t t e n t i o n were g i v e n t o m i n i m i z i n g e x p o s u r e f o r t h e same number o f d a y s and y e a r s , t h e r i s k o f an exposed worker a c q u i r i n g cancer might r i s e t o as h i g h as one chance i n 24,000. Analysis A c c o r d i n g t o t h e d a t a s u b m i t t e d by t h e r e g i s t r a n t t o t h i s D e p a r t ment, when m i c e w e r e f e d c h l o r d i m e f o r m , a s i g n i f i c a n t i n c r e a s e i n t h e i n c i d e n c e o f m a l i g n a n t h e m a n g i o e n d o t h e l i o m a s was o b s e r v e d as compared t o the c o n t r o l mice. T h i s tumor i n c i d e n c e i s p r e s e n t e d i n Table I. Table I . M a l i g n a n t Hemangioendothelioma I n c i d e n c e Induced by Chlordimeform i n Mice Dose L e v e l 0 20 100 500

(pom)

Male 1/42 0/42 15/47 39/47

Female 1/41 2/44 22/44 35/46

Combined 2/83 2/86 37/91 74/93

Dr. Bernard Hanes, our C o n s u l t i n g B i o s t a t i s t i c i a n , a s s i s t e d us i n c a r r y i n g out a s e r i e s of r i s k e s t i m a t e s based on t h i s mouse b i o assay d a t a , u s i n g t h r e e r e c o g n i z e d m a t h e m a t i c a l models ( m u l t i - h i t , m u l t i - s t a g e , and o n e - h i t ) . T a b l e I I p r o v i d e s a p r i n t - o u t of " p o i n t e s t i m a t e " doses a t g i v e n response v a l u e s ( r i s k ) . W i t h t h e d a t a p r e s e n t e d i n T a b l e I I , i t i s p o s s i b l e t o make r i s k e s t i m a t i o n s , by i n t e r p o l a t i o n , f o r workers who are exposed t o c e r t a i n l e v e l s of chlordimeform. T a b l e I I I shows cancer r i s k assessments f o r c h l o r d i m e f o r m exposure based on u r i n a r y e x c r e t i o n of c h l o r d i m e f o r m i n man and m a l i g nant tumor i n c i d e n c e from the mouse b i o a s s a y study (male and f e m a l e mice d a t a combined). T h r e e commonly u s e d m a t h e m a t i c a l m o d e l s ( m u l t i - h i t , m u l t i - s t a g e , and o n e - h i t ) a r e used i n the r i s k e s t i m a tions.


32.

M A D D Y ET A L .


463

Table I I . Computer Output of Risk Assessment Data


L·—From Risk ÏÔ; 10"; 10 ; 10 ;? 10"; 10"; 10

Male Mpuse Dafra Multi-Hit 7798 1.44 2.62 χ 10"* 4.79 χ 10"; 8.74 χ 10"; 1.60 χ ΙΟ"* 2.91 χ 10"

Estimated Dose (ppm) Multi-Stage One-Hit 3765 " 3TÔÔ " 3.64 χ 10"J 2.99 χ 10"* 3.64 χ 10", 2.99 χ 10"; 3.64 χ 10"; 2.99 χ 10"; 3.64 χ 10"* 2.99 χ 10"* 3.64 χ 10"f 2.99 χ 10"* 3.64 χ 10 2.99 χ 10

I I . From Both Sexes Combined Data Estimated Dose (ppm) Risk Multi-Hit Multi-Stage One-Hit 10", 2.79 2.89 2.89 io"; 2.72 χ i o " ; 2.88 χ i o " i 2.88 χ i o " i 10"; 2.66 χ 1 0 " ; 2.88 χ i o " ; 2.88 χ i o " ; lO'l 2.60 χ 10"; 2.88 χ 10"; 2.88 χ i o " ; 10"° 2.54 χ 10"; 2.88 χ 10"; 2.88 χ 10"; 10"; 2.49 χ 10"f 2.88 χ 10"^ 2.88 χ 10 ;? 10" 2.43 χ 10 2.88 χ 10 2.88 χ 10

Table I I I . Worker's Cancer Risk Due to Chlordimeform Exposure Chlordimeform Levels i n Urine 50 ppb (0.05 ppm)

Multi-Hit 2.2 χ 10" (1 i n 450 Κ)

Multi-Stage One-Hit 2.1 χ 1 0 " 2 . 1 χ 10" (1 i n 480 Κ) (1 i n 480 Κ)

100 ppb (0.1 ppm)

4.4 χ 10" (1 i n 230 Κ)

4.2 χ 10" (1 i n 240 Κ ) *

4.2 χ 10" (1 i n 240 K)

250 ppb (0.25 ppm)

1.1 χ 10" (1 i n 91 Κ)

1.0 χ 10" (1 i n 100 Κ)

1.0 χ 10" (1 i n 100 K)

500 ppb (0.5 ppm)

2.2 χ 10" (1 i n 45 Κ)

2.1 χ 10" (1 i n 48 Κ)

2.1 χ 10" (1 i n 48 K)

1,000 ppm

(1 ppm)

6

6

5

5

5

6

5

5

Ό

6

5

5

4.4 χ 10" 4.2 χ 10" 4.2 χ 10" (1 i n 23 Κ) (1 i n 24 Κ) (1 i n 24 K) *For instance, this means a p r o b a b i l i t y of 1 i n 240,000 of inducing cancer i n one worker due to chlordimeform exposures. 5

5


5

D E R M A L E X P O S U R E R E L A T E D TO PESTICIDE USE

464 The f o l l o w i n g a s s u m p t i o n s estimates : 1)


2)

3) 4) 5) 6) 7)

w e r e made t o c a l c u l a t e t h e a b o v e r i s k

Humans a r e as s e n s i t i v e t o the c a r c i n o g e n i c e f f e c t s of c h l o r d i meform as are the l a b o r a t o r y mice. F o r t h e mouse, 1 ppm c h l o r d i m e f o r m i n t h e d i e t e q u a l s 0.1 mg c h l o r d i m e f o r m per k i l o g r a m o f body weight based on average f o o d intake. A v e r a g e worker weight i s 70 kg (154 pounds). The average amount of u r i n e e x c r e t e d per day i s 1.5 l i t e r s . E x p o s u r e t o c h l o r d i m e f o r m w i l l o c c u r f i v e d a y s p e r week, 10 weeks i n a y e a r , and f o r 10 y e a r s of a 70-year l i f e span. C a r c i n o g e n i c e f f e c t i s d e t e r m i n e d by t h e t o t a l a c c u m u l a t e d dose, i . e . , (dose) χ ( t i m e ) = tumor y i e l d . Based on human and l a b o r a t o r y a n i m a l d a t a , t h e amount o f c h l o r dimeform measured i n u r i n e r e p r e s e n t s 35% of the d e r m a l l y a b s o r b e d dose.

D u r i n g t h e summer o f 1982, t h e C a l i f o r n i a D e p a r t m e n t o f Food and A g r i c u l t u r e ' s W o r k e r H e a l t h and S a f e t y U n i t s t a f f m o n i t o r e d w o r k e r ' s e x p o s u r e a s s o c i a t e d w i t h t h e u s e o f c h l o r d i m e f o r m as a p e s t i c i d e on c o t t o n i n I m p e r i a l C o u n t y , C a l i f o r n i a , u n d e r a v e r y t i g h t l y r e g u l a t e d exposure r e d u c t i o n program. T a b l e IV g i v e s a summary o f c h l o r d i m e f o r m (as a n i l i n e d e r i v a t i v e s ) m e a s u r e d i n t h e u r i n e of workers i n v o l v e d i n a p p l i c a t i o n s of t h i s p e s t i c i d e . Table IV. Summary of t h e L e v e l s o f Chlordimeform Measured i n the U r i n e of Workers I n v o l v e d i n A p p l i c a t i o n s of t h i s P e s t i c i d e i n I m p e r i a l County i n 1982

T o t a l Number of Samples

U r j n e Sample

Average Chlordimeform L e v e l s ppm**

"A" samples o n l y ( u r i n e c o l l e c t e d at end of workshift)

537

0.12

"B" samples o n l y ( u r i n e c o l l e c t e d 8-12 hours a f t e r end of w o r k s h i f t )

556

0.10

"A" and "B" samples

1,093

0.11

"A" and "B" samples ( h i g h e r of the two values only) **A11 n o n - d e t e c t e d l i m i t of d e t e c t i o n .

598

0.13

l e v e l s w e r e g i v e n t h e v a l u e o f 0.05

ppm,

the

T a b l e IV shows t h a t the a v e r g e c h l o r d i m e f o r m l e v e l s among t h e u r i n a r y s a m p l e s t a k e n a r e i n t h e r a n g e o f 100 t o 130 ppb (0.10 t o 0.13 ppm). The cancer r i s k f o r a worker h a v i n g been exposed t o t h i s amount o f c h l o r d i m e f o r m can be e s t i m a t e d from t h e d a t a p r e s e n t e d i n



32.

M A D D Y ET A L .


465

T a b l e I I I . For e x a m p l e , i f a worker has a u r i n e c o n c e n t r a t i o n of 100 ppb o f c h l o r d i m e f o r m , t h e e x t r a r i s k o f a c q u i r i n g cancer due t o c h l o r d i m e f o r m e x p o s u r e i s a p p r o x i m a t e l y 1 i n 240,000 a c c o r d i n g t o the m u l t i - s t a g e model. For t h e m a j o r i t y of the m o n i t o r e d workers whose u r i n a r y c h l o r d i m e f o r m l e v e l s w e r e b e l o w 50 ppm, their i n c r e a s e d r i s k might be as low as 1 i n 500,000. Due t o the i n t r i n s i c u n c e r t a i n t y a s s o c i a t e d w i t h t h e mathematic a l e x t r a p o l a t i o n , f r o m a few a n i m a l d a t a p o i n t s t o a l o w d o s e r e s p o n s e , t h e r i s k shown i n T a b l e I I I f r o m e x p o s u r e t o a s p e c i f i c l e v e l o f c h e m i c a l s h o u l d be c o n s i d e r e d as a p r o b a b i l i t y d i s t r i b u t i o n or r i s k p r o f i l e . For example, f o r a r i s k w i t h a "best p o i n t - e s t i m a t e " o f 10" , t h e r e m i g h t be a f i v e p e r c e n t c h a n c e t h a t t h e t r u e l e v e l o f r i s k m i g h t be one o r two o r d e r s o f m a g n i t u d e g r e a t e r o r s m a l l e r than the p o i n t - e s t i m a t e v a l u e . Thus, f o r t h e person e x c r e t i n g an a v e r a g e l e v e l o f 1 ppm c h l o r d i m e f o r m i n u r i n e , f o r t h e c o n d i t i o n s t h a t a p p l y i n T a b l e I I I f o r the m u l t i - s t a g e model, the i n c r e a s e d r i s k of a c q u i r i n g cancer has a 95% p r o b a b i l i t y of b e i n g i n the range between 1 chance i n 240 and 1 chance i n 2,400,000. A l t h o u g h t h e s e s t a t i s t i c a l methods are c u r r e n t l y b e i n g used t o e s t i m a t e cancer r i s k , because o f the s m a l l number of a n i m a l s exposed and t h e s m a l l numbers o f d o s e l e v e l s u s e d , c o n s i d e r a b l e c a u t i o n s h o u l d be e x e r c i s e d not t o o v e r - i n t e r p r e t t h e s e s t a t i s t i c a l e s t i mates o f what w i l l happen i n a b i o l o g i c a l system such as the exposed person. An a d d i t i o n a l v a r i a b l e not d e a l t w i t h c o m p l e t e l y i n these r i s k a n a l y s e s , i s t h e expected type o f tumor. The tumors produced i n t h e mouse w e r e h e m a n g i o e n d o t h e l i o m a s i n t h e a b d o m i n a l o r g a n s and t i s s u e s . A n i l i n e r e s i d u e s p a s s i n g t h r o u g h t h e human b l a d d e r a r e suspect as h a v i n g the p o t e n t i a l of p r o d u c i n g more s e r i o u s tumors at t h i s s i t e . T h i s v a r i a b l e adds t o t h e u n c e r t a i n t y o f c a n c e r r i s k assessment f o r human exposure based on l a b o r a t o r y a n i m a l data.

R E C E I V E D N o v e m b e r 14, 1984


Risk Assessment of Excess Pesticide Exposure to Workers in

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