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Advances in the Unified Field Model for Reentry Hazards WILLIAM J. POPENDORF Agricultural Medical Research Facility, University of Iowa, Iowa City, IA 52242 This paper summarizes the development and application of both a philosophic and quantitative framework for unifying research approaches and findings in residue decay, exposure assessment, and cholinesterase response (Popendorf & Leffingwell, Res. Rev. 82:125, 1982). Examples are provided for using this model to interpret the potential cholinesterase response from a known foliar residue and to establish reentry intervals to prevent excessive cholinesterase inhibi tion. The potential and limitations of extrapolating this approach to other settings i s also discussed, as are the needs for future research to support a compre hensive approach to pesticide use, residues, and exposure controls. Exposure o f h a r v e s t e r s t o p e s t i c i d e r e s i d u e s on c r o p s and t h e i r f o l i a g e has been d i s c u s s e d as a h a z a r d f o r 35 y e a r s ( 1 ) . This h a z a r d has come t o be c a l l e d the " r e e n t r y p r o b l e m " . Two y e a r s ago L e f f i n g w e l l and I p u b l i s h e d a comprehensive r e v i e w o f the r e s e a r c h and r e g u l a t o r y approaches s u r r o u n d i n g the " r e e n t r y p r o b l e m " i n an e f f o r t t o s y n t h e s i z e a u n i f y i n g framework t o the o t h e r w i s e d i v e r s e a s p e c t s o f t h i s f i e l d worker problem ( 2 ) . B o r r o w i n g from E i n s t e i n and v i e w i n g t h i s framework as a s e m i - e m p i r i c a l model r a t h e r than a t h e o r y , I c a l l e d t h i s s y n t h e s i s the " u n i f i e d f i e l d m o d e l " . T h i s paper w i l l d i s c u s s (a) how t o use t h i s model i n p r a c t i c e , (b) some r e c e n t r e s e a r c h r e l a t i n g t o t h i s m o d e l , and (c) new r e s e a r c h suggested by t h i s m o d e l . U s i n g the U n i f i e d F i e l d Model The c o n c e p t s comprised w i t h i n the " u n i f i e d f i e l d model" a r e embodied i n F i g u r e 1. The 1982 r e p o r t (2) d i s c u s s e d each o f the measurable c o n d i t i o n s o f r e s i d u e , d o s e , and response (the boxes i n F i g u r e 1) and the p r o c e s s e s o r mechanisms (arrows) w h i c h connect them. The u n i f i e d f i e l d model went beyond a concept to a sequence
0097-6156/ 85/0273-O323$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.
Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985.
MECHANISM
DECAY
IfeSIDUE
ENVIRONMENTAL MECHANISM
EXPOSURE DOSE
WORKER
Model. 1980,
MECHANISM
TOXICOLOGY
F i g u r e 1. C o n c e p t u a l diagram o f the U n i f i e d F i e l d (Reproduced w i t h p r e m i s s i o n from Ref. 15. Copyright American I n d u s t r i a l Hygiene A s s o c i a t i o n . )
APPLICATION
RESPONSE
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m
C/5
G
m
α
H
C/i
m
α
m
m r
73
m
73
C
> r m χ -α Ο
73
m
α
23.
Field Model for
Reentry
Hazards
325
o f f o r m u l a e w h i c h c h a r a c t e r i z e the mechanisms r e l a t i n g the o r i g i n a l r e s i d u e (R ) to the r e s i d u e a t r e e n t r y ( R ) , the d e p o s i t e d dose ( D ) , the p e r t i s s u e mass (D), and the a c e t y l c h o l i n e s t e r a s e r e s p o n s e (AAChE). Thus, the u n i f i e d f i e l d model f o r organophos phate (OP) p e s t i c i d e s was a l s o p o s t u l a t e d as E q u a t i o n s 1-4, T a b l e I. The form o f the r e s i d u e decay E q u a t i o n 1 i s s i m p l i f i e d from decay p a t t e r n s i n the r e a l w o r l d , b u t i t i s c h a r a c t e r i s t i c (2$3). Among the v a r i o u s r e s i d u e exposure assessment s t u d i e s , an e m p i r i c a l l i n e a r r e l a t i o n s h i p between r e s i d u e and dose has been found ( 2 ) . At l e a s t f o r OP p e s t i c i d e s , c h o l i n e s t e r a s e i n h i b i t i o n (ΔAChE) i s w e l l e s t a b l i s h e d and a c c e p t e d as a r e s p o n s e c r i t e r i o n ( 2 , 4 , 5 ) , a l t h o u g h not w i t h o u t e x c e p t i o n (2 p. 133).
8ose
1
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Unified
POPENDORF
Table
I . Q u a n t i t a t i v e Form o f U n i f i e d F i e l d R D D AAChE
1
where
= = =
Model
R exp (-k Τ) (1) k? t R (2) k D'/m (3) l - exp (-k D / L D ) (4) Γ
a
5Q
= the r e s i d u e a t any p o i n t i n time a f t e r a p p l i c a t i o n
R
= the i n i t i a l d e p o s i t e d r e s i d u e , e.g.
R
yg/cm
2
ο p e s t i c i d e s p e c i f i c r e s i d u e decay
k
coefficient
r Τ
reentry i n t e r v a l ,
days
D»
= d e p o s i t e d dose (mg)
k
= crop s p e c i f i c r e s i d u e t r a n s f e r c o e f f i c i e n t , cm /hr
on h a r v e s t e r ' s s k i n 2
d t
D
as
-
work (exposure) p e r i o d , h r a d s o r b e d o r absorbed dose p e r body mass, mg/kg
= a b s o r p t i o n c o e f f i c i e n t f o r f r a c t i o n absorbed
k a m AAChE
body mass (nominal
= f r a c t i o n o f RBC
kg)
cholinesterase inhibited
enzyme c o e f f i c i e n t
k
70
(use 6.0
when u s i n g
topical
e dermal dose and L D
50
k -1.0) a dermal dose t o k i l l h a l f o f a group o f t e s t r a t s
The t e m p o r a l sequence o f e v e n t s i n the r e a l w o r l d p r o g r e s s e s t h r o u g h F i g u r e 1 from l e f t - t o - r i g h t ; and i f one were t o make r e a l - t i m e d e c i s i o n s based on a known r e s i d u e , then one would use E q u a t i o n s 1 to 4 i n the same o r d e r as shown. However, from the p o i n t o f v i e w o f a r e e n t r y p o l i c y and s e t t i n g r e e n t r y i n t e r v a l s , one must p r o c e e d from r i g h t - t o - l e f t , and from E q u a t i o n 4 t o 1. In e i t h e r c a s e , one o f the b a s i c elements i n an o c c u p a t i o n a l h e a l t h d e c i s i o n i s e s t a b l i s h i n g an a c c e p t a b l e l e v e l o f r e s p o n s e ; i n t h i s c a s e , an a c c e p t a b l e AAChE. A c c e p t a b l e l e v e l s o f c h o l i n e s t e r a s e i n h i b i t i o n have been d i s c u s s e d b e f o r e C2,5) and have been a d o p t e d i n t o a t l e a s t one governmental s t a n d a r d ( 6 ) . The concept o f r e g u l a t i n g o c c u p a t i o n a l work p r a c t i c e s on the b a s i s o f a b i o l o g i c r e s p o n s e i s tenuous a t
Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985.
DERMAL EXPOSURE RELATED TO PESTICIDE USE
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326
best, especially i f the l e v e l of exposures i s highly variable and the time-frame and p o t e n t i a l f o r disabling or l e t h a l doses i s great. For instance i n C a l i f o r n i a , medical surveillance of pesticide manu facturers, formulators, and applicators i s l e g a l l y required, and RBC AChE i n h i b i t i o n i s r e s t r i c t e d to 40% of an i n d i v i d u a l ' s baseline a c t i v i t y (6). Using Equation 4 and data compiled i n the o r i g i n a l review (2), one can calculate that a single dose s u f f i c i e n t to i n h i b i t 40% AChE i s only a factor of 2 less than would begin to cause disabling c l i n i c a l symptoms (60%) and 3x less than the LD^ ( l e t h a l to 1% of exposed group of r a t s ) ( 7 ) . On the other hand elaborating on Equation 4 and depending upon the b i o k i n e t i c s of enzyme reversion (reversible i n h i b i t i o n ) f o r a given OP, 2 to 3 consecutive d a i l y doses each s u f f i c i e n t to i n h i b i t 40% of the AChE w i l l also produce 60 to 80% i n h i b i t i o n and s i m i l a r c l i n i c a l symptoms. And f i n a l l y i t w i l l be shown i n Figure 3, that consecutive d a i l y i n h i b i t i o n s of less than 2% may result i n a progressive depletion of 40% AChE after 8 weeks. Based on a general knowledge of the frequency of medically monitored workers being administratively removed from further ex posure and a cursory review of the few f a t a l i t i e s reported i n C a l i f o r n i a , one might conclude that cholinesterase i n h i b i t i o n can occur both progressively and from acute over-exposures. Routine cholinesterase monitoring among harvesters would suffer the same limitations and require such extensive administrative procedures as to be as poorly received by labor as by farm managers. It i s , i n f a c t , the goal of a reentry i n t e r v a l policy to provide equivalent f i e l d worker protection without requiring blood monitoring. Establishing a control c r i t e r i o n should include a consideration of the same range of exposure patterns: from variable exposures with intermittent high peaks to consistent but low d a i l y exposures. There i s reason to believe that both acute and progressive i n h i b i t i o n has occurred among C a l i f o r n i a harvesters, that progressive i n h i b i t i o n can occur nationwide, and that condi tions f o r both probably exist worldwide. Examples of reentry-response calculations f o r several reported residues were provided i n my 1982 paper (2). A more generalized and p r a c t i c a l set of examples w i l l be followed here. To begin with, l e t us f i r s t discuss issues related to R · Some general l i m i t s and guidelines can be constructed based on plane geometry and mass balance. For instance, a 1 pound pesticide a p p l i c a t i o n distributed uniformly onto a f l a t 1 acre f i e l d (1 lb ΑΙΑ) would result i n an average i n i t i a l residue of 11 yg/cm . The amount of foliage per acre varies by crop, size of plants, and plant spacing; f o r instance, data by T u r r e l l (8) indicate c i t r u s foliage can comprise roughly 1.5 to 4 times the land surface area upon which the trees are planted. Thus, such i n i t i a l deposits on c i t r u s foliage might i d e a l l y range from 7 to 3 pg/cm . Other mechanisms such as d r i f t , f o l i a r versus ground deposition, gallonage of water and runoff, evaporation while drying, f o l i a r absorption, etc w i l l further reduce i n i t i a l residues. Reported f i e l d measurements vary from near the i d e a l to well below: an a p p l i c a t i o n of 1 lb ΑΙΑ captan on strawberries (9) i s l i k e l y to result i n an i n i t i a l residue of 6 to 10 yg/cm of projected leaf area (or 3 to 5 yg/cm counting both sides); f o r parathion on c i t r u s (3), 1 yg/cm (or 0.5 counting both sides); and some more closely planted, t a l l crops such as tobacco (10,11) may range from 1.0 to 0.1. 2
2
2
2
2
Honeycutt et al.; Dermal Exposure Related to Pesticide Use ACS Symposium Series; American Chemical Society: Washington, DC, 1985.
23.
POPENDORF
Unified
Field
Model for
Reentry
327
Hazards
Hazard assessments can be made of t h i s i n i t i a l residue using the u n i f i e d f i e l d model with decay time, T, set equal to zero days. Figure 2 provides an overview of the anticholinesterase potential calculated from known residues as follows: (1) Find R from Equation 1 or equivalent tables or figures. In our case, T>0, therefore R=R =1.0 pg/cm , corresponding to c i t r u s . (2) Find the skin dose, D', from Equation 2 . The dosing c o e f f i c i e n t k i s crop (and work practice) s p e c i f i c , and may also be affected by residue penetration through clothing worn i n d i f f e r e n t regions. Table II provides a summary of known and extrapolated values of k,. For p r a c t i c a l purposes i n our example, l e t ^=5000 cm /hr and t=8 hours, the nominal U.S. customary workday, even though i n any given s i t u a t i o n i t may be more or l e s s . (3) Find the tissue dose, D. The use of Equations 3 and 4 depends upon the chemical, i t s target organ, and the e f f e c t . For OPs when using dermal L D ^ Q i n Equation 4, the absorption c o e f f i c i e n t (k ) must be assumed to be 1.0 since f r a c t i o n a l dermal absorption rates are accounted f o r within the dermal LD_ versus say intraperitoneal or intravenous · The use of an o r a l L D ^ Q adds even more confounding differences and should be avoided within t h i s setting. For other non-cholinergic e f f e c t s , a known f r a c t i o n a l absorption c o e f f i c i e n t could be incorporated ( 2 , pp 157). A nominal 70 kg (154 lb) average man should be assumed i f dosing calculations are to be based on one of the nominal 1.9 m skin area models C 2 , pp 155). (4) Find the cholinesterase response using k =6. This response i s a change from whatever pre-exposure a c t i v i t y was present (possibly already depressed from previous exposures). For multiple, simultaneous OP exposures the sum of the individual doses over t h e i r respective L D ^ Q S i s calculated (e.g. -k D./LD_ .) before taking the exponent ( 2 ) . 2
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0
2
n
2
n
2
Table I I . Summary of K, dosing c o e f f i c i e n t values (cm /hr) to predict harvester dose mg/hr from residue pg/cm based on projected leaf area ( r e f . 2^JL) t o t a l leaf area (ref. 13) 2
o r
via
Crop citrus peach grape strawberry tomato (mechanical) a) b) c) d)
projected A a
5,000 1,900, 1,600° 4,ooo
