190.
PESTICIDE RESIDUES I N MAMMALIAN
T I S S U E S , PROBLEMS, I N C I D E N C E , A N D CONTROLS
H.
U.S.
F.
KRAYBILL
PUBLIC HEALTH SERVICE
WASHINGTON.
D. C.
P R E S E N T E DB Y :
HOWARD BOflD
U.S. P U B L I C H E A L T H S E R V I C E
_ _ _ _ _ _ _ _ _ _ _ - - - - - _ - - - - - - - - I.
INTRODUCTION
The p r o l i f e r a t i o n of a g r i c u l t u r a l chemicals i n t o t h e environment
of man and animals has been accelerated by g r e a t technological advances of
t h e p a s t two decades. Considerable e f f o r t has been made i n o u r economy t o
a s s u r e man a more abundant supply of food and f i b e r through t h e u t i l i z a t i o n
of p e s t i c i d e chemicals. By c o n t r o l l i n g t h e environment of domestic animals
and man with chemical agents a concomitant problem of environmental p o l l u t i o n
has a r i s e n of which man has become acutely aware s i n c e it r e l a t e s t o t h e
h e a l t h of human populations, f i s h , w i l d l i f e , and domestic animals. Perhaps
public awareness of p e s t i c i d e environmental contamination was increased
through e a r l i e r recognition of hazards of f a l l o u t r a d i o a c t i v i t y . More r e c e n t l y research i n t h e f i e l d of environmental h e a l t h sciences has focused
a t t e n t i o n on n a t u r a l l y occurring contaminants such as fungal metabolites
and b a c t e r i a l t o x i n s . With increasing a t t e n t i o n t o problems of environmental p o l l u t i o n it i s not s u r p r i s i n g t h a t Rachel Carson's " S i l e n t Spring"
stimulated a t h r u s t f o r c o n t r o l programs a t l o c a l and Federal l e v e l s . Cert a i n l y a more balanced account of t h e o v e r a l l problem of environmental
p e s t i c i d e contaminants and residues w a s portrayed i n t h e P r e s i d e n t ' s Science
Advisory Committee Report on "Use of Pesticides" (1).
Environmental p o l l u t i o n may involve t o t a l exposure of man o r a n i mals t o a p a r t i c u l a r s t r e s s or a combination of s t r e s s agents. The r e s u l t a n t exposure and b i o l o g i c a l challenge can a r i s e from t h r e e sources: from
i n h a l a t i o n , absorption, or ingestion, o r a combination of a l l t h r e e exposure
routes simultaneously.
11. EQUILIBRIUM BETWEEN ENVIRONMENTAL AND BODY LEVELS OF PESTICIDES
There i s a balance between t h e l e v e l of a p e s t i c i d e i n t h e environment and t h e r e t e n t i o n i n t h e mammalian body, but t h i s i s dependent upon
s e v e r a l v a r i a b l e s which may o r may not permit a d i r e c t r e l a t i o n s h i p . Species
d i f f e r e n c e , influence of sex, age, 'and o v e r a l l metabolic d e v i a t i o n s i n cert a i n instances y i e l d some discontinuity i n e s t a b l i s h i n g an i d e a l l i n e a r r e l a t i o n s h i p a t l e a s t on t h e b a s i s of animal s t u d i e s . In a d d i t i o n , having
d a t a on t i s s u e r e t e n t i o n l e v e l s , intake l e v e l s , and b i o l o g i c a l responses
associated w i t h i n t a k e and r e t e n t i o n i n animals (and t h i s c e r t a i n l y holds f o r
meat animals) it might be possible t o e x t r a p o l a t e these f i n d i n g s t o t h e i r
e f f e c t s on man. These e f f e c t s might be delineated i n terms of a c u t e and
chronic t o x i c i t y , physiological response or ultimate r e t e n t i o n l e v e l s and
t o t a l body burden of p e s t i c i d e s .
191.
The introduction o f p e s t i c i d e s i n t o t h e environment of domestic
animals may occur through s e v e r a l procedures : (a) p e s t c o n t r o l operations
i n buildings and o t h e r protected s h e l t e r s , (b) mosquito abatement and f o r e s t
i n s e c t spray programs, ( c ) d i r e c t p a r a s i t e control programs i n animals, and
(d) i n s e c t c o n t r o l on p l a n t crops; t h e crops o r forage l a t e r u t i l i z e d as
animal feed which may contain a p e s t i c i d e residue, (e) contaminated water
s u p p l i e s . The exposure of domestic animals i s not too unlike t h a t of man
involving i n h a l a t i o n , absorption, o r ingestion, with t h e exception t h a t
a c c i d e n t a l exposure and acute poisonings may occur t o man through h i s occup a t i o n a l use of a wide spectrum of p e s t i c i d e s .
The low l e v e l prolonged exposure t o p e s t i c i d e chemicals of e i t h e r
man o r animal does not e l i c i t a s e a s i l y recognizable o r dramatic response o r
symptomology as acute exposure. Environmental c o n t r o l of t h e long term exposure may a l s o be somewhat d i f f i c u l t . Chronic e f f e c t s may u s u a l l y be ascribed t o those compounds having a "persistence" q u a l i t y o r extended r e s i d u a l
behavior. The c l a s s o f i n s e c t i c i d a l compounds described as organochlorine
o r "chlorinated hydrocarbons," because of t h e i r high s o l u b i l i t y and a f f i n i t y
f o r body depot f a t , where they are stored and not r e a d i l y metabolized, a r e
u s u a l l y considered f o r t h e i r p o t e n t i a l chronic e f f e c t s . b r e recently, however, t h e l e s s p e r s i s t e n t , r e a d i l y metabolizable organophosphorus compounds
which may present repeated challenges o r poisoning episodes, a r e now being
viewed as having c a p a b i l i t i e s f o r sustained adverse h e a l t h e f f e c t s . Because
of t h e p o t e n t i a l human h e a l t h hazard posed by p e s t i c i d e residues i n e d i b l e
t i s s u e s of meat animals, game, f i s h o r o t h e r food products, t h i s a r e a of
concern has f o s t e r e d comprehensive toxicological research programs.
Chlorinated hydrocarbon and organophosphorus i n s e c t i c i d e s which
a r e sprayed on meat animals may be absorbed through t h e s k i n and u l t i m a t e l y
s t o r e d i n t h e adipose t i s s u e . Through ingestion o f i n s e c t i c i d e contaminated
feeds, storage o f p e r s i s t e n t p e s t i c i d e occurs i n t h e body f a t o r i s excreted
i n the m i l k of d a i r y cows.
The U.S. Department o f Agriculture, cognizant of t h e need t o help
p r o t e c t t h e h e a l t h o f man and animals and t o preserve t h e food and f i b e r
supplies from t h e ravages of p e s t s , issued an o f f i c i a l policy on p e s t i c i d e s
i n 1964 ( 2 ) . In essence, it i s t h e policy of t h a t Department t o promulgate
and use p e s t c o n t r o l programs which provide t h e l e a s t p o t e n t i a l hazard t o
man and animals. If r e s i d u a l p e s t i c i d e s must be used t o control o r eliminate
p e s t s they a r e t o be used i n minimal e f f e c t i v e amounts applied only t o t h e
i n f e s t e d area and a t minimal e f f e c t i v e frequency. This d i r e c t i v e f u r t h e r
s t a t e s t h a t b i o l o g i c a l , ecological o r c u l t u r a l methods o r non-persistent
and low t o x i c i t y p e s t i c i d e s w i l l be used whenever such means a r e f e a s i b l e
and w i l l s a f e l y and e f f e c t i v e l y control o r eliminate t a r g e t p e s t s . A s a p a r t
of t h i s v i g i l a n c e i n p e s t control it i s a l s o emphasized that i n t h e protect i o n of human h e a l t h a l l users of p e s t i c i d e s w i l l avoid unnecessary exposure
of crops, l i v e s t o c k , f i s h and w i l d l i f e .
111. METABOLISM AND RETENTION OF INSECTICIDES
There i s a paucity of knowledge and data on t h e metabolic f a t e o f
p e s t i c i d e s . This l a c k o f understanding of t h e physiological processes involved with various chlorinated hydrocarbon compounds which leave residues
i n human and animal t i s s u e s and t h e blood and milk of marmnalian species i s
unfortunate. Most of t h e data accrued was developed i n support of various
p e s t i c i d e r e g i s t r a t i o n s where information was required relevant t o U.S.
Food and Drug Administration tolerances. The uncontrolled a p p l i c a t i o n of
i n s e c t i c i d e s with r e s u l t a n t contamination of feeds i s a grave economic and
h e a l t h problem s i n c e t h i s leads t o accumulation of p e r s i s t e n t type p e s t i c i d e s
o r t h e i r metabolites i n t h e t i s s u e s of meat animals. The organochlorine
i n s e c t i c i d e s such as a l d r i n , DDT, d i e l d r i n , endrin, and heptachlor repres e n t t h e most s e r i o u s problem in terms o f the high r e t e n t i o n rates of these
compounds i n animal adipose t i s s u e s as they a r e received through t h e food
chain s i n c e meat and meat products a r e consumed by humans and, i n t u r n ,
contribute t o t h e t o t a l body burden of these compounds i n man. According
t o Claborn e t a 1 ( 3 ) when i n s e c t i c i d e s a r e f e d t o beef c a t t l e and sheep a s
a feed contaminant a t dosages l i k e l y t o occur as residues on forage crops,
a l l except methoxychlor a r e s t o r e d i n t h e f a t . The order of t h e i r storage
i s as follows :
aldrin
-;z
d i e l d r i n ===- heptachlor epoxide > BHC
chlordane - 1 i n d a n e - a e n d r i n
DDT ==.
>heptachlor>toxaphene
The accumulation of t h e l i p i d soluble chlorinated hydrocarbons
i n adipose t i s s u e of animals can occur from d i r e c t treatment with i n s e c t i cides a s well as through ingestion of i n s e c t i c i d e contaminated forage crops
o r pasture. The U.S. Food and Drug Administration has granted tolerance
l e v e l s f o r p e s t i c i d e s i n t h e f a t from various animals including c a t t l e ,
goats, hogs, horses, p o u l t r y (malathion only) and sheep. These tolerance
l e v e l s a r e l i s t e d i n Table 1. Tolerance l e v e l s f o r p e s t i c i d e residues i n
forage (alfalfa) a r e presented i n Table 2 .
The Meat Inspection Division of the Consumer and Marketing
Service of t h e U.S. Department of Agriculture i s responsible f o r inspect i o n , approval, o r r e j e c t i o n of meat and meat food products from animals
slaughtered and/or processed a t Federally inspected p l a n t s , t o assure t h a t
such products w i l l be f r e e of o r within s a f e tolerances of harmful biologic a l agents and p e s t i c i d e residues. Memorandum No. 316 (Part 311.27 of t h e
Manual of Procedures) was issued by the Meat Inspection Division on Novemb e r 10, 1964. This memorandum provides f o r i n s t r u c t i o n s and standards o f
compliance f o r t h e inspectors i n charge of meat inspection, owners and
operators of o f f i c i a l establishments, and others t o be a b l e t o c a r r y o u t
t h e i r r e s p o n s i b i l i t i e s i n assuring t h a t meat and meat food products do not
exceed s a f e tolerances of p e s t i c i d e residues.
The Meat Inspection Division has a b i o l o g i c a l residue surveillance
program consisting of an objective, a s e l e c t i v e , and an i n v e s t i g a t i v e phase.
The objective phase i s t h e random s e l e c t i o n of t i s s u e s of animals slaughtered
a t Federally inspected establishments f o r a n a l y s i s of chemicals and drugs.
This program provides leads on trends and suggests need f o r s e l e c t i v e
sampling. The s e l e c t i v e phase i s t h e a n a l y s i s of animal t i s s u e s when a
s p e c i f i c b i o l o g i c a l residue problem has been i d e n t i f i e d through t h e object i v e phase of t h e program. Some f e a t u r e s of t h e s p e c i a l i n v e s t i g a t i v e work
w i l l be r e f e r r e d t o l a t e r under control and research programs on residues.
A s previously indicated, t h e r e i s l i t t l e information a v a i l a b l e i n
the l i t e r a t u r e on t h e metabolism o f organochlorine compounds with t h e
193.
TABU 1
OFFICIAL FDA TOLERANCES
FOR SOME PESTICIDE LEVELS I N MEAT FAT
Pesticide
A.
B
*
.
To l e ram e
PPm
Species
Organochlorine
DMI
7
C a t t l e , goats, hogs, horses
and sheep
Lindane
4
Hogs
Lindane
7
C a t t l e , goats, horses and sheep
Methoxychlor
3
C a t t l e , goats, hogs, horses
and sheep
Toxaphene
7
C a t t l e , goats, hogs, horses
and sheep
Carbophenothion
0.1
C a t t l e , goats, hogs and sheep
Dioxathion
1
C a t t l e , goats, hogs, horses
and sheep
Diaz inon
0.75
C a t t l e and sheep
Co-Ral (chlorinated)*
1
C a t t l e , goats, hogs, horses,
sheep and p o u l t r y
Guthion*
0.1
C a t t l e , goats and sheep
Linuron
1
C a t t l e , goats, hogs, horses
and sheep
Malathion*
4
C a t t l e , goats, hogs, horses,
sheep and p o u l t r y
Organophospho rus
Meat o r meat by-products
194.
TABLE 2
OF’FICIAL FDA TOLERANCES
FOR SOME PESTICIDE RESIDUES I N ALFALFA*
Pesticide
Tolerance (ppm)
Chlo r i n a t ed hydro carbons
Methoxychlor
100
Organophosphorus
Demeton
5
Diazinon
10
Guthion
2
Malathion
135
Parathion
1
Carbamates
Carbaryl (Sevin)
100
Miscellaneous
Diuron
*
2
P o s i t i v e l e v e l s only given, zero values f o r a l d r i n , d i e l d r i n , heptachlor
(epoxide)
exception of DDT (4). Considering t h e l a r g e group and c l a s s e s of p e s t i c i d e
compounds i n our environment, t h i s suggests t h e need f o r intensive research.
There a r e s i m i l a r i t i e s i n t h e metabolic f a t e of a few compounds i n a s i n g l e
species b u t one cannot extrapolate findings on a s i n g l e compound i n one
species t o a wider range of i n s e c t i c i d a l compounds. Q u i t e i l l u s t r a t i v e of
t h i s p o i n t a r e t h e d a t a of Claborn e t a 1 (5) shown i n Table 3, where a l d r i n
and d i e l d r i n were f e d t o c a t t l e and sheep, including both sexes, f o r f o u r
and e i g h t weeks. It i s o f i n t e r e s t t o note the v a r i a t i o n i n f a t l e v e l s of
a l d r i n and/or d i e l d r i n i n s t e e r s , h e i f e r s , wethers, and ewes a f t e r 4 t o 36
weeks following t h e feeding period. For t h e c a t t l e t h e v a r i a t i o n between
male and female body r e t e n t i o n l e v e l s was not a s marked a s t h a t f o r t h e
sheep, where t h e wethers appeared t o r e t a i n more of t h e p e s t i c i d e than t h e
ewes. The sheep appeared t o r e t a i n a higher l e v e l o f p e s t i c i d e f o r a longer
period of t i m e .
Further emphasis on t h e species difference i n t h e metabolism of
d i e l d r i n i s represented i n t h e d a t a of Gannon e t a 1 (6) shown i n Table 4,
where’lambs presented t h e l o w e s t residue of d i e l d r i n and p o u l t r y the highest
195.
TABLE 3
PPM OF PESTICIDE RESIDUES I N FAT OF VARIOUS MEAT ANIMALS
DURING AM) AFTER FEEDING ALDRIN AND DIELDRIN
Weeks of Feeding
4
8
A.
B.
4
Weeks a f t e r Feeding
8
20
32
36
Aldrin
Steers
70
63
68
55
25
10
Heifers
80
86
67
36
15
9
Wethers
39
70
58
37
32
33
Ewe 6
48
68
43
45
32
Steers
58
79
46
36
19
9
He if e rs
41
77
56
21
7
-
Wethers
60
77
-
36
46
25
31
33
Ewes
60
79
67
30
25
14
11
31
10
Dieldrin
-
Claborn, H. V., Ebwers, J. W., Wells, R. W., Radeleff, R. D. and
Nickerson, W. J . , Agr. Chemicals, 37-40, Aug. 1953.
r e t e n t i o n of d i e l d r i n i n body f a t . Some of the p e s t i c i d e residue i s , of
course, found i n the m i l k of l a c t a t i n g animals as w e l l as i n meat f a t .
The data from s t u d i e s o f Gannon e t a1 (7) shown i n Table 5 r e f l e c t the
comparative storage l e v e l s of d i e l d r i n i n milk and body f a t of cows experimentally f e d d i e l d r i n i n t h e i r r a t i o n .
These feeding experiments provide some assessment of t h e r e l a t i v e
r a t i o s of t h e amount of p e s t i c i d e deposited in body t i s s u e s , organs, and
body f l u i d s r e l a t e d t o l e v e l of p e s t i c i d e i n t a k e . For example, i n Table 6
t h e f a t storage r a t i o s f o r a l d r i n and d i e l d r i n f o r various species a r e
shown. These data a l s o i l l u s t r a t e that t h e r e i s a v a r i a t i o n in t h e metabol i s m o r r e t e n t i o n o f p e s t i c i d e s a m n g various mammalian and avian species.
Chickens apparently have a low turnover rate whereas t h e bovine, f o r example, have a much higher r a t e of excretion o r less r e t e n t i o n of p e s t i c i d e
residues. There a r e no experimentally controlled s t u d i e s on man which
would permit c a l c u l a t i o n of a f a t storage r a t i o , b u t f r o m c a l c u l a t i o n s on
d i e t a r y intakes and r e s u l t a n t adipose tissue l e v e l s o f organochlorine
i n s e c t i c i d e s it i s assumed t h a t man's f a t storage r a t i o i s similar t o t h a t
o f t h e r a t and t h e cow.
196.
TABLE 4
STORAGE OF DIELDRIN I N TISSUES OF DIFFERENT ANIMALS
Dieldrin i n
Diet
(PPd
Hens
Dieldrin i n F a t (ppm)
Hogs
Steers
Lambs
0.25
10.2
0.8
0.4
0.4
0.75
35.7
3.5
2.8
0.6
8.7
4.3
1.7
-
2.25
Gannon, N., Link, R. P., and Decker, G. C.
826-828 (1959)
-
J. Agr. Food Chem. 7
TABLE 5
BODY STORAGE I N COWS FED DIELDRIN I N THEXR DIET
Levels Fed (ppm)
Levels i n Milk (ppm)
(after 84 days)
Levels i n F a t (ppm)
( a f t e r 84 days)
0.10
0.02
0.20
0.25
@.06
0.90
0.75
0.11
1.70
2.25
0.28
4.80
Gannon, N.,
Link, R. P., and Decker, G. C.
824-826 (1959)
Agr. and Food Chem. 7
TABU 6
FAT STORAGE RATIO FOR INSECTICIDES FED TO MAMMALIAN AND AVIAN SPECIES’
Species
Pesticide fed
Dog
Dieldrin
R a t (Male)
Aldrin
R a t (Female)
Aldrin
Steers
Aldrin
COWS
Aldrin
Steers
Dieldrin
cows
Dieldrin
Chickens
Dieldrin
Wimm F a t Storage Ratio
ppm i n F a t
ppm i n Diet
17
3
5
6
5
4
3
40
k a l c u l a t e d frum various r e p o r t s on feeding s t u d i e s on p e s t i c i d e s .
197.
The a f f i n i t y of unmetabolized p e s t i c i d e s f o r c e r t a i n t i s s u e s i s
important i n evaluating residue l e v e l s encountered i n meat o r meat products
consumed by man. Visceral organs such as l i v e r , kidney, and h e a r t r e t a i n
l e v e l s of p e s t i c i d e s comparable t o t h e l e a n t i s s u e o r muscle. It i s assumed t h a t p e r s i s t e n t p e s t i c i d e s a r e occluded i n t h e f a t t i s s u e of these
organs. Kitselman e t a 1 (8) and Ely e t a 1 (9) have shown i n t h e i r d a t a
presented i n Table 7 t h a t c a t t l e f e d 1 . 5 ppm of d i e l d r i n i n hay deposited
one t e n t h t h a t amount i n l i v e r , kidney, and l e a n meat, b u t t h e d i e l d r i n
was concentrated a t twice t h i s l e v e l i n t h e adipose t i s s u e . Further conc e n t r a t i o n , a s might be expected, was r e f l e c t e d i n t h e b u t t e r made from
cream and m i l k from cows f e d d i e l d r i n .
The organophosphorus and carbamate i n s e c t i c i d e s , since they a r e
rapidly metabolized, do not present t h e residue problem of t h e organochlorine i n s e c t i c i d e s which r e a d i l y deposit i n depot f a t a r e a s .
TABU 7
STORAGE O F DIELDRIN I N CATTLE
FED HAY CONTAMINATED WITH 1 . 5 ppm OF DIELDRIN
0 rgan
Dieldrin Residue ppm
Liver
0.1
Kidney
0.2
Lean Meat (Muscle)
0.1
Adipose Tissue (Fat)
3 .O
Milk
->
Cream 4 Butter
Kitselman, C . H . ,
378 (1950)
Dahm, P. A.,
5.7
and Borgmann, A. R .
Ely, R. E., Moore, L. A., Hubanks, P. E.,
J. Dairy S c i . 37 294 (1954)
-
9.5
Am. J . o f Vet. Res. 1
1
-
Carter, R. H., and Poos, F. W.
Claborn e t a 1 (10) i n some experimental spray programs on c a t t l e , sheep,
goats, and hogs, using one percent Sevin ( c a r b a r y l ) , a carbamate spray
s o l u t i o n f o r control of t i c k s and horn f l i e s , found some absorption o f t h e
p e s t i c i d e . On t h e f i r s t day a f t e r spraying, t h e concentration i n t i s s u e s
of swine was q u i t e low a t 0.04 ppm b u t goats showed a higher l e v e l of
carbaryl i n muscle and b r a i n t i s s u e than c a t t l e , sheep, o r swine. O f significance i s t h e f a c t t h a t i n 7 days t h e p e s t i c i d e was metabolized i n a l l
t i s s u e s (adipose, muscle, l i v e r , kidney, and b r a i n ) t o very low l e v e l s
(Table 8 ) . Some i n s e c t c o n t r o l spray programs, p a r t i c u l a r l y those i n
rangelands o r f o r e s t s , have an e f f e c t on t h e residue levels in f i s h i n
streams contiguous t o the spray a r e a and a l s o t h e game animals. I n Table 9
198.
some data obtained by t h e Idaho Fish and Game Department, working coopera t i v e l y with t h e U.S. Department of Agriculture, demonstrate t h a t DDT l e v e l s
in body f a t of deer, goat, and e l k increased manyfold from t h i s exposure
(200-2000 f o l d i n c r e a s e ) . One beef animal i n t h e area showed a DDT body
f a t l e v e l approaching t h e tolerance value o f 7 ppm f o r t h i s p e s t i c i d e .
There i s now a t r e n d t o s h i f t away from p e r s i s t e n t p e s t i c i d e s i n these
a r e a s not only due t o t h e residue problem i n game b u t a l s o because of t h e
high r e t e n t i o n by s h e l l f i s h i n estuarine waters.
Surveillance o f market meat and meat product samples has been
q u i t e l i m i t e d . Y l s t monitoring o f slaughtered animals i s c a r r i e d o u t by
t h e Meat Inspection Division o f t h e U.S. Department of Agriculture,
TABLE 8
CARBARYL RESIDUES I N SOME TISSUES OF CATTLE, SHEEP, GOATS, AND
HOGS AFTER FOUR SPRAYINGS WITH 1.0% CARBARYL
Time After
Spraying
Oment a1
Fat
ppm Carbaryl i n Tissues
lhs c l e
Liver
Kidney
0.00
0.10
Brain
CATTLE
1 Day
7 Days
1 Day
7 Days
0.57
0.13
< 0.04
<0.04
0.21
0.07
C0.04
SREEP
(0.04
0.10
<0.04
<0.04
(0.04
0.04
0.15
<0.04
<0.04
<0.04
(0.04
0.06
23 .O
< 0.04
0.04
<O. 04
<0.04
<0.04
GOATS
1 Day
7 Days
0.38
0.70-0.90
0.18
(0.04
0.30
SWINE
1 Day
<0.04
<0.04
(0.04
Claborn, H. V . , Roberts, H. D., Nmn, H. D., Bowman, M. C . , Ney, M. C . ,
Weidenbach, C. P. and Radeleff, R . D. Agr. and Food Chem. 11 74-76
(1963)
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b u t l i t t l e of t h e s e d a t a has been released i n journal p u b l i c a t i o n s o r rep o r t s . The high tolerances f o r some chlorinated hydrocarbon i n s e c t i c i d e s
from a regulatory standpoint reduce t h e incidence of unlawful residue
l e v e l s . According t o S t r e e t (11)t h e S t a t e of C a l i f o r n i a made a survey of
p e s t i c i d e residues i n various meat products i n 1963. O f 94 samples t e s t e d
none was found wherein DIYT exceeded t h e tolerance and 22 were found t o be
negative. Some beef and pork f a t samples contained from 1 . 7 t o 8 . 8 ppm of
DDT + DDD + DDE. A similar survey conducted i n 1964 indicated t h a t 8 7 percent of 1 7 7 samples showed no more than a t r a c e (0.1 ppm) of DDT residue.
One sample of beef f a t showed DDT over t h e tolerance and another beef f a t
sample had 0.3 ppm heptachlor and 0 . 2 ppm heptachlor epoxide.
Samples of beef and pork assayed f o r DDT +DDE by t h e Milk and
Food Research Laboratories of t h e U.S. Public Health Service a t the
S a n i t a r y Engineering Center i n Cincinnati, Ohio, showed values corresponding t o t h e C a l i f o r n i a survey. The range i n values of DM' + D D E i n pork as
reported by Campbell e t a1 (12) f o r southeast, northeast, and northwest
USA was from 0.26 t o 0.53 ppm with mean values ranging from 0.093 t o 0.114
ppm (Table 1 0 ) . The l e v e l s of DDT + DDE reported by same i n v e s t i g a t o r s
f o r beef samples where somewhat lower ranging from 0.01 t o 0.25 ppm of
DDT + DDE with a mean of 0.14 ppm.
TABLE 10
ORGANOCHLORINE HYDROCARBONS I N BEEF
Location
No. of
Samples
Min
Southeast
7
Northeast
2
DDE 4 DDT (ppm)
Max
Mean
Det
0.25
0.14
De t
0.01
-
ORGANOCHLORINE COMPOUNDS I N PORK
DDE
DDT (pprn)
Ybx
Location
No. of
Samples
Min
Sou theas t
15
N.D.
0.53
0.109
No rthwe st
10
N.D.
0.22
0.093
Northeast
7
0.05
0.26
0.114
Camphel1,J. E.> Richardson, L. A . , and Schafer, M. L.
10 831-836 (1965)
Health -
+
Arch Environ
Mean
201.
IV.
REDUCTION OF RESIDUES AND DEPLETION OF INSECTICIDE STORAGE
Due t o t h e increased public h e a l t h concern r e l e v a n t t o t h e body
burden o f p e s t i c i d e s , p a r t i c u l a r l y t h e chlorinated cyclodiene i n s e c t i c i d e s
suck as a l d r i n , d i e l d r i n , endrin, and heptachlor, recent i n v e s t i g a t i o n s have
been accelerated and provide evidence of important developments i n t h i s
a r e a . A reduction o f 72 percent i n d i e l d r i n storage i n rat t i s s u e was
obtained by S t r e e t (13) through administration of DDT. Earlier workers
(14, 15) showed t h e influence of DDT i n d e t o x i f i c a t i o n o f a v a r i e t y of
drugs which p a r a l l e l s t h e e f f e c t i v e n e s s of DDT on d i e l d r i n s t o r a g e .
Various drugs were t r i e d by S t r e e t e l a1 (16) t o reduce d i e l d r i n
s t o r a g e and t h e s e were q u i t e e f f e c t i v e i n some experiments with rats. I n
Table 11 i t i s noted t h a t h e p t a b a r b i t a l , aminopyrine, and tolbutamide reduced t i s s u e d i e l d r i n i n rats f e d 1 ppm of d i e l d r i n i n t h e d i e t f o r 10 days.
Hence s u i t a b l e drugs might be used not only t o reduce i n s e c t i c i d e residues
i n animals, e s p e c i a l l y those providing meat, b u t might a l s o be q u i t e e f f e c t i v e i n reducing t h e i n s e c t i c i d e body s t o r e s i n man, p a r t i c u l a r l y i n t r e a t ment of i n d i v i d u a l s undergoing heavy occupational exposure t o p e s t i c i d e s .
The i n s e c t i c i d e a l d r i n and heptachlor a r e transformed i n t o t h e
expoxides d i e l d r i n and heptachlor epoxide, r e s p e c t i v e l y . Biologically,
as a c l a s s , epoxides a r e o f c ~ n c e r nbecause some epoxides a r e carcinogenic
TABLE 11
DRUG EFFECTS ON DIELDRIN STORAGE I N RATS
(Administration of 1 ppm Dieldrin i n d i e t f o r 10 days)
Storage
Reduction
T i s sue
u g h
Dieldrin
9 SE
Control
7.53
0.89
DDT 4 mg/kg
2.06
0.34
72
60 mg/kg
6.54
0.47
13
Tolbutamide 290 mg/kg
3.20
0.72
57
Aminopyrine
75 mg/kg
2.76
0.39
63
Aminopyrine 350 mg/kg
1.40
0.09
81
Heptabarbital
40 rg/kg
4.01
0.67
47
Heptabarbital 225 mg/kg
1.50
0.07
80
Treatment
Tolbutamide
S t r e e t , J. C .
6-15
(1966)
, Wang,
M. and Blau, A . D.
k
-
B u l l of Env Contam and Tox 1
202.
o r mutagenic. Toxic epoxides have been viewed as not undergoing d e t o x i f i c a t i o n b u t are considered as s t o r e d i n t h e depot f a t from which s i t e they
a r e u l t i m a t e l y excreted i n t h e f e c e s ( 1 7 ) . This has been pointed o u t i n
metabolic s t u d i e s conducted by T e r r i e r e e t a1 (18). Korte e l a1 (19) have
shown t h a t a major p o r t i o n of d i e l d r i n t h a t i s f e d i s excreted by way of t h e
b i l e as an u n i d e n t i f i e d hydrophilic compound.
A s mentioned e a r l i e r , t h e U.S. Department of Agriculture i s
carrying on an a c t i v e i n v e s t i g a t i v e program r e l a t i n g t o regulatory c o n t r o l
of chemical and/or b i o l o g i c a l residues i n t h e e d i b l e t i s s u e s of food producing animals. For example, feeding p o u l t r y l i t t e r t o l i v e s t o c k has been
s t u d i e d i n terms of residues l e f t i n meat animals a t time of ante-mortem
inspection. In t h e a p p l i c a t i o n of p e s t i c i d e s , p a r t i c u l a r l y by a e r i a l spraying which may include organochlorine and organophosphorus i n s e c t i c i d e s ,
e d i b l e t i s s u e s of animals have been checked t o a s c e r t a i n the e f f e c t s o f
a p p l i c a t i o n p r a c t i c e s on l i v e s t o c k . The p r a c t i c e of using paradichlorobenzene as a deodorant spray i n garbage f e d t o swine has been i n v e s t i g a t e d because t h i s chemical leaves a residue and odor i n pork. Some extensive
research i s a l s o being c a r r i e d o u t t o a s c e r t a i n t h e v a r i a t i o n i n organochlorine compounds such as DMI s t o r e d i n t h e f a t l o c a t e d a t various anatomic a l s i t e s of an a n i m a l ’ s body.
From a p r a c t i c a l viewpoint much can be done i n the way of control
toward reduction of residues i n e d i b l e t i s s u e s . Such considerations r e l e vant t o p e s t i c i d e s involve the a p p l i c a t i o n of presumed s a f e dosage l e v e l s
and s t r i c t observance of whatever time i n t e r v a l s may be necessary between
a p p l i c a t i o n of materials and s l a u g h t e r t o insure elimination of r e s i a d e s .
With r e s p e c t t o a p p l i c a t i o n , t h i s implies e i t h e r chemicals used on l i v e s t o c k
o r on p l a n t m a t e r i a l s which may be l a t e r consumed by l i v e s t o c k . Certainly
c l o s e s u r v e i l l a n c e must be maintained t o guarantee t h a t drinking water
f a c i l i t i e s and feed a r e not inadvertently contaminated.
Although t h e
p r a c t i c e of using so-called “ t r a s h feeds” such as apple o r vegetable pomace
has been discouraged because these products have exhibited highly concent r a t e d p e s t i c i d e residues, t h e r e must be continuous v i g i l a n c e t o p r o h i b i t
the use of such contaminated products. I d e a l l y , l i v e s t o c k producers could
maintain low residues by continuous assay of feeds, b u t t h i s requirement
may not be f e a s i b l e e s p e c i a l l y f o r average producers.
Various attempts have been made t o discover if any treatments a r e
e f f e c t i v e i n reduction of residues i n e d i b l e t i s s u e s t o be consumed by man.
In some recent unpublished r e p o r t s g a m a i r r a d i a t i o n processing of f i s h and
o t h e r marine products has been proposed f o r d e s t r u c t i o n of t h e chlorinated
hydrocarbon i n s e c t i c i d e residues. Despite any o p t i m i s t i c claims it i s q u i t e
u n l i k e l y from a t e c h n i c a l viewpoint t h a t ionizing r a d i a t i o n could e f f e c t i v e l y
degrade t h e molecule of DDT, f o r example, s i n c e the cross s e c t i o n of such a
compound does not provide a s u i t a b l e t a r g e t f o r e f f e c t i v e d e s t r u c t i o n . Heat
treatment of meats has been s t u d i e d and Ivey e t a 1 (20) have found t h a t t h e
cooked f a t from beef r o a s t s contained e s s e n t i a l l y t h e same d i e l d r i n concent r a t i o n as t h a t determined i n carcass body f a t (Table 1 2 ) .
V.
RELATIONSHIP OF ANIMAL TISSUE RESIDUES TO
BODY BURDEN O F PESTICIDE RESIDUES I N MAN
The s i g n i f i c a n c e of t h e residue problem i s evaluated u l t i m a t e l y i n
terms of man’s p o t e n t i a l source of exposure through ingestion of these
203.
ccmpounds i n t h e human d i e t . Although t h e general population receives some
exposure t o p e s t i c i d e s i n t h e environment v i a absorption, i n h a l a t i o n , and
i n g e s t i o n , Kraybill ( 2 1 ) has estimated t h a t 90 percent of t h e i n d i v i d u a l ' s
t o t a l ingested p e r s i s t e n t p e s t i c i d e arises from p e s t i c i d e i n t a k e i n food.
Drinking water i s estimated t o f u r n i s h only 0.02 percent of t o t a l ingested
pes t i c i d e s
.
O f t h e major d i e t a r y components such as d a i r y products, veget a b l e s , c e r e a l products, meats, seafood, and eggs, a l l o f which may have
d e t e c t a b l e l e v e l s of organochlorine i n s e c t i c i d e residues, meats, seafood,
and eggs as a c l a s s c o n t r i b u t e approximately 58 percent of t h e t o t a l
DDT 9 TIDE i n t a k e according t o Campbell and co-workers (12). Considering
t h e f a c t t h a t meat and meat products c o n s t i t u t e about 20 percent of man's
t o t a l d a i l y i n t a k e , with eggs and seafood representing only a minor f r a c t i o n
TABLE 1 2
DE3LDRIN I N FAT FROM BEEF CARCASSES COMPAFBD WITH
DIELDRIN LEVELS I N FAT FROM BEEF ROASTS
( C a t t l e Fed Varying Levels of Aldrin and Dieldrin)
Sample No.
Carcass Body F a t
Dieldrin
Renal F a t
PPm
Cooked Fat
from Roasts
1
0.99
0.88
1.40
2
3.38
2.90
3.23
3
8.50
7.84
7.80
4
39.20
44.50
33.30
Ivey, M. C . , Claborn, H. V., Mann, H. D.,
Agr. and Food Chem. 9 374-376 (1961)
Radeleff, R. D. and Woodard, G. T.
compared t o meats, it i s conceivable t h a t meat and meat products alone may
contribute a t l e a s t 50 percent of t h e t o t a l d a i l y d i e t a r y i n t a k e of ins e c t i c i d e residues (Table 13).
Various i n v e s t i g a t o r s have surveyed t h e t o t a l d i e t s i n s e l e c t e d
l o c a t i o n s and i n s t i t u t i o n s i n t h e United S t a t e s , including households,
r e s t a u r a n t s , and j a i l s , t o a s c e r t a i n the t o t a l d a i l y i n t a k e of DDT and DDE
( 2 2 , 23, 24 and 2 5 ) . Although t h e r e was some variance i n t h e t o t a l DDT i n take from household and r e s t a u r a n t meals, t h e household meals i n some a g r i c u l t u r a l a r e a s contained a somewhat higher l e v e l of DDT, due perhaps t o
s p e c i a l t y o r unprocessed home grown items of higher r e s i d u e s . The average
t o t a l d a i l y i n t a k e of DDT found by these i n v e s t i g a t o r s was 0.184 mg. Simil a r l y t h e average d a i l y i n t a k e of DMI f o r inmates o f a penal i n s t i t u t i o n was
0.202 mg.
204.
The f i n d i n g t h a t d i e t , and p a r t i c u l a r l y meat o r meat products,
has an influence on t o t a l DDT intake and r e s u l t a n t body l e v e l s i n man has
been f u r t h e r corroborated by i n v e s t i g a t i o n s o f Hayes e t a 1 (25). O f s i g nificance i s t h e f a c t t h a t Hayes and co-irorkers (25) found in eleven meatless
meals t h a t were sampled t h a t t h e mean t o t a l d a i l y intake was only 0.041 mg
(Table 14). Specimens of retained preserved adipose t i s s u e from 1 0 cadavers
c o l l e c t e d a t museums and h o s p i t a l s during t h e e r a preceding use of DDT have
shown on assay, as expected, zero l e v e l s of t h i s p e s t i c i d e . Since t h e
TABLE 13
ESTIMATED DDT
+
DDE CONTRIBUTIONS OF MAJOR DIETARY COMPONENTS
Weekly
Consumpt i o n (kg)
Commodity
Group
Conc
DDT + DDE
(PPd
9
Weekly
DET + DDE
Intake (mg)
of
Total
DDT +DDE
Milk
3.5
0.01
0.035
3.7
Other d a i r y products
0.3
0.50
Ve g e t ab 1e s
16.5
2.6
0.05
0.15
0.13
14.4
Meats, seafood, eggs
2.6
0.20
0.52
57.6
Cereals
0.9
0.03
0.027
2.9
0.05
*
0.045
4.9
0.9
-
Others
TOTAL
10.8
100.0
0.907
*Whole d i e t calculated t o contain 0.08 ppm DDT + DDE
Campbell, J. E . , Richardson, L. A., and Schafer, M. L .
Health 10 831-836 (1965)
-
Arch Environ
TABLE 1 4
PESTICIDE RESIDUES I N TOTAL DIET
SURVEYED AT VARIOUS INSTITUTIONS I N USA
No. of
Meals
Source
Penal I n s t i t u t i o n 1
Mean
Total Daily Intake
DDT
DDE
(md
(md
16
0.202
0.050
25
0.184
0.092
12
0.038
0.044
Household (1961-62)3
17
0.299
0.173
Meatless Meals4
1
1
0.041
Restaurant and I n s t i t u t i o n (1954)
Res t a u r a n t (1961-62)
2
-
1. Hayes, W. J . , Durham, W. F. and Cueto, C . J. J.A.M.A.
1 6 2 890 (1956)
2. Walker, K. C., Goette, M. B. and Batchelor, G. S. Ag and Food Chem 2
1035 (1954)
3. Curham, W . F., Armstrong, J . F. and Quinby, G. E. Arch Environ Health
11 641-647 (1965)
4 . Hayes, W. J . , Quinby, G. E., Walker, K. C . E l l i o t t , J. W. and Upholt,
W. M. Arch Ind Health 18
- 398 (1958)
205.
introduction o f DDT, however, the general population receiving an environmental exposure of t h i s p e s t i c i d e has shown i n 6 1 cases examined on unr e s t r i c t e d meat d i e t s t h a t t h e average DDT l e v e l i n adipose t i s s u e has been
observed t o be c o n s i s t e n t l y a t 4 . 9 ppm. However, f o r 1 6 cases surveyed who
had meatless d i e t s t h e body burden was 2 . 3 ppm o r roughly 50 percent of t h a t
shown f o r people on a meat d i e t . If meat was consumed only twice a month
the adipose t i s s u e l e v e l was approximately t h e same as f o r those who remained on a meatless d i e t . If t h e intake of meat was increased from twice
a month t o twelve times a month t h e r e was a s l i g h t r i s e i n the average bcdy
burden o f DDT, from 2.3 t o 2 . 8 ppm (Table 1 5 ) .
The introduction of organochlorine i n s e c t i c i d e s f o r p e s t vectored
d i s e a s e c o n t r o l and crop p r o t e c t i o n i n 1941 revealed an increase i n environmental l e v e l s o f these p e s t i c i d e s . Accordingly t h i s was r e f l e c t e d i n the
appearance of these chemicals i n t h e body t i s s u e s and a gradual increase i n
t h e body burden of t h e s e p e r s i s t e n t p e s t i c i d e s , as shown i n Figure 1. It
has been maintained by some i n v e s t i g a t o r s t h a t peak concentrations were
reached i n 1950, a f t e r which t h e r e w a s a steady decline and plateauing i n
p e s t i c i d e l e v e l s . However, others have held t h a t t h e maximum concentration
i n human adipose t i s s u e was reached i n 1955, followed by a decline and
TABLE 1 5
BODY BURDEN OF ORGANOCHLORINE PESTICIDES
I N MAN A S INFLUENCED BY DIET
Average Levels of Pesticides (ppm)
Dietary Exposure
No. Cases
DDT
DDE
P r i o r t o DDT Era
10
Zero
Zero
Meatless Diet
16
2.3
3.2
4
2.8
4.5
61
4.9
6.1
Meat l e s s than twice monthly
General Population
Unrestricted Meat Diet
Hayes, W. J . , Quinby, G. E., Walker, K. C . , E l l i o t t , J. W. and Upholt, W. M.
Arch Ind Health 18
- 398 (1958)
plateauing i n p e s t i c i d e l e v e l s representing t h e presence of these environmental contaminants continuously during t h e l a s t t e n y e a r s . A p l o t of mean
l e v e l s o f DDT derived materials i n adipose t i s s u e o f t h e general population
i n USA, a s shown i n Figure 1, would appear t o support t h e v a l i d i t y of t h e
l a t t e r concept (26, 27, 28, 29 and 30).
Curing t h e period 1958 t o 1965 various surveys i n Europe, Asia,
t h e Middle East, and t h e United S t a t e s have been made t o determine t h e
206.
average concentration of DDT derived materials i n the adipose t i s s u e of the
general populations i n various countries. A s i l l u s t r a t e d i n Figure 2,
England appears t o present t h e lowest body burden f o r DDT 9 DDE whereas
s e v e r a l areas i n India revealed 25 t o 30 ppm of DDT + DDE i n t h e body f a t
of t h e general population. In t h e l a t t e r case these higher body f a t l e v e l s
f o r DDT +DDE a r e c e r t a i n l y a r e f l e c t i o n of higher environmental contaminat i o n enhanced by vigorous p e s t control programs such a s mosquito abatement
p r o j e c t s . The lower l e v e l s of DDT
DDE i n body f a t of Europeans are i n d i c a t i v e of t h e s t r i n g e n t controls on t h e use of p e r s i s t e n t organochlorine
i n s e c t i c i d e s i n those countries which moreover i s r e f l e c t e d i n decreased
environmental l e v e l s and diminution of residues i n l o c a l l y grown food and
forage crops (30, 31, 32, 33, 34, 35, 36, 3 7 and 38).
The influence of a g r i c u l t u r a l chemicals and s p e c i f i c a l l y chemical
p e s t i c i d e s on the q u a l i t y o f o u r environment has been aore f u l l y recognized
r e c e n t l y due t o public concern regarding environmental p o l l u t i o n and i t s
r e l a t i o n s h i p t o t h e h e a l t h of man, f i s h , w i l d l i f e , and domestic animals.
Whether p e s t i c i d e exposure involving any o f these species occurs through
i n h a l a t i o n , absorption, o r ingestion, t h e r e appears t o be an equilibrium
between environmental and body l e v e l s of p e s t i c i d e s . The organochlorine
o r so-called p e r s i s t e n t type i n s e c t i c i d e s have been implicated i n t h e
residue problem. The more r e a d i l y metabolizable o r non-persistent organic
phosphate i n s e c t i c i d e s , although highly t o x i c t o man and animals, do not
present the v a r i e t y of problems encountered i n t h e u t i l i z a t i o n o f residue
producing i n s e c t i c i d e s . These l a t t e r types of compounds, although affording long-term p r o t e c t i o n i n p e s t control do, however, n e c e s s i t a t e s t r i n g e n t
c o n t r o l s i n t h e i r a p p l i c a t i o n and close surveillance with respect t o t o l e r ances. Wherever f e a s i b l e , l a r g e - s c a l e p e s t c o n t r o l programs have promulgated t h e use o f non-persistent p e s t i c i d e s t o obviate t h e occurrence o f
residues which have t h e c a p a b i l i t y f o r sustained adverse h e a l t h e f f e c t s .
For t h e p r o t e c t i o n of human h e a l t h , a l l u s e r s o f p e s t i c i d e s should be repeatedly i n s t r u c t e d t o avoid unnecessary exposure of crops, l i v e s t o c k ,
f i s h , and w i l d l i f e .
Despite extensive research on t h e t o x i c i t y of p e s t i c i d e s t h e r e i s
a l a c k of understanding and information on the physiological processes i n volved w i t h organochlorine i n s e c t i c i d e s which leave residues i n animal and
human t i s s u e s . The r a t e o f metabolism and f a t e of these compounds v a r i e s
i n c e r t a i n species and i s influenced by sex, hormones, c e r t a i n drugs, and
i n t e r a c t i o n s with o t h e r p e s t i c i d e s , a l l o f which r e l a t e t o t h e degree of
r e t e n t i o n i n adipose t i s s u e s and various organs.
The human d i e t controls t o a l a r g e degree the body burden of
r e s i d u a l p e s t i c i d e s , a t l e a s t among persons non-occupationally exposed. A
major d i e t a r y contributor t o p e s t i c i d e exposure by ingestion i s meat, which
represents approximately 50 percent of t h e ingested p e s t i c i d e . In some
l i m i t e d surveys of market meats a high percentage of samples had only t r a c e
amounts of DDT, with some few samples of pork and beef containing l e v l s
ranging from 1 t o 7 ppm of DDT which d i d not exceed the tolerance s e t f o r
this pesticide
.
207.
Various methods f o r reduction o f residues and depletion o f p e s t i cide storage have been t r i e d experimentally, such a s the use of DDT t o decrease body l e v e l s of d i e l d r i n , and t h e use o f drugs such as aminopyrine,
h e p t a b a r b i t a l , and tolbutamide, which have proved q u i t e e f f e c t i v e . There
a r e many o t h e r more p r a c t i c a l methods than these procedures t h a t can be
applied t o reduce residues i n meats, most o f which involve c o n t r o l of environmental contamination and s t r i c t adherence t o u t i l i z a t i o n of low residue
feed s t u f f s .
The t r e n d i n u t i l i z a t i o n o r discontinuance of p e r s i s t e n t p e s t i cides i s discussed i n terms of t h e a l t e r a t i o n of t h e body burden of these
p e s t i c i d e s i n man. The decrease i n body f a t l e v e l s of DDT over the p a s t
2 5 years can be ascribed t o reported reduction i n volume of u s e of these
r e s i d u a l p e s t i c i d e s i n a g r i c u l t u r a l and public h e a l t h c o n t r o l programs.
The p a t t e r n s of t h e use of the organochlorine i n s e c t i c i d e s a r e r e f l e c t e d
i n t h e body f a t l e v e l s o f DDT i n countries throughout t h e world. Countries
having more r e s t r i c t i v e programs on u t i l i z a t i o n and a p p l i c a t i o n of chlorina t e d hydrocarbon i n s e c t i c i d e s appear t o present a lower body f a t residue
of DDT and s i m i l a r organochlorine i n s e c t i c i d e s i n adipose t i s s u e sampling
of t h e general population than i n t h o s e areas where l e s s r e s t r i c t i v e use
occurs.
FIGURE I
Mean L e v e l s o f DDT C e r i v e d M a t e r i a l s i n Adipose T i s s u e
(1942-1965)
o f t h e General P o p u l a t i o n i n U.S.A.
20-
15
-20
- Hayes e t a l (1958)
- Laug e t a1 (1951)
- Hayes e t a1 (1956)
- Hayes e t (1958)
- Quinby e t a1 (1965)
- - Davies e t al (1965)
1942
1950
1955
1956
1961-62
1965
21
-15
- 10
\
Y L - - _ - --
1940
1945
I
1950
I
-5
\
1955
- - - & - - - - - -@-.
I
I
1960
1965
DDT +DDE
DDT
.
Y e a r s o f O b s e r v a t i o n and DDT E x p o s u r e
a-
o
- - CI
- - -A
- - -
-0
v)
.-Q
L
c
U
a =
E O
+ o
C Q )
o w
c
m
U
m
U
aJ
=
W
0
0
I-
9
n
a
a
U
d
Q:
0
cv
W
m
aJ
m
C
m
a
-
W
0
0
9
n
In
L
z
Q:
c3
S
a
z
-
W
m
Q)
C
m
E
ul
m
W
m
5
A
209.
W
+
a
a
n
n
c-
e
'TJ
(Q
I-
o
n
O
Y-
E
a
n.
210.
BIBLIOGRAPHY
Report on Use of P e s t i May 15, 1963 Washington, D. C.
1. The P r e s i d e n t ' s Science Advisory Committee:
c i d e s , G.P.O.
.
.
2.
Secretary, U. S Dept of Agriculture, Secretary' s Memorandum No. 1565,
USDA Policy on P e s t i c i d e s , December 23, 1964.
3.
Claborn, H. V., R. D. Radeleff and R. C. Buehland, P e s t i c i d e Residues
i n Meat and Milk, a Research Report, USDA Report ARS-33-63,
Dec. 1960.
4.
Hayes, W. J., DDT, t h e I n s e c t i c i d e Dichlorodiphenyltrichloroetbane
and Its Significance - (S. W. Simmons Ed) Vol. 11, Birkhauser,
Base1 1959.
5.
Claborn, H. V., J. W. BOwers, R. W. Wells, Radeleff, R. D. and
Nickerson, W. J. Agr. Chemicals 37-40 Aug. 1953.
6.
Gannon, N., R. P. Link, and G. C . Decker, J. Agr. Food Chem. 7 826-828
(1959)
7.
7 824-826
Gannon, N., R. P. Link and G. C. Decker, J. Agr. Food Chem. (1959)
8.
Kitselman, C. H., P. A. Dahm, and A. P. Borgmann Am J. of Vet. Res.
11 378 *l950)
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9.
Ely, R. E. , L. A. Wore, P. E. Ilubanks, R. H. C a r t e r and F. W. Poos,
J. Dairy Sci. 37 294 (1954)
.
H. D. Roberts, H. D. Mann, M. C. Bowman, M. C. Ney,
P. Weidenbach and R. D. Radeleff Agr. and Food Chem. 11 74-74
(1963)
10. Claborn, H. V.,
C
11. S t r e e t , J. C. Surveillance of P e s t i c i d e s i n t h e Environment (Domestic
Animals) Idaho Annual Health Conference Proceedings P e s t i c i d e s ,
People and Programs 64-71 (May 1965)
12.
Campbell, J. E., L. A. Richardson, and M. L. Schafer, I n s e c t i c i d e
Residues i n t h e Human Diet Archives Env. Health 10 831-836
(1965)
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S t r e e t , J. C.,
14.
Hart, L. G. and J. R. Fouts, Proc. SOC. EXp. Bio. Med. 114 388 (1963)
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Science 140 1580
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15. Remmer, H., Proc. F i r s t I n t . Pharmacological Meeting 6 235
Pergamon Press, Oxford
(1962)
16. S t r e e t , J. C . , M. Wang and A. D. Blau, Drug E f f e c t s on Dieldrin Storage
in R a t Tissue B u l l . of E m . Contamination and Toxicology 1 No. 1
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211.
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Chem. 4
T. J. DeCino, N. W. Earle and Y. P. Sun, J . Agr. Food
937-941 (1956)
18.
Terriere, L. C., G. H. Arscott, and U. Kiigemagi
502-504 (1959)
J. Agr. Food Chem. 7
19.
Kbrte, F., G. Ludwig and J. Vogel
20.
Ivey, M. C., H. V. Claborn, H. D. Mann, R. D. Radeleff and G. T.
Woodard Agr. and Food Chem. 9 374-376 (1961)
21.
Kraybill, H. F. P e s t i c i d e s and Public Health Proceedings o f the
Michigan S t a t e Medical Society Centennial, Detroit, Michigan,
Sept. 1965.
22.
Hayes, W. J . , W. F. Durham and C . Cueto, The E f f e c t o f Known Repeated
162 890 (1956)
Oral Doses of DDT i n Elan J.A.M.A.
23.
Walker, K. C., M. B. Goette and G. S. Batchelor, Dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene content of
prepared meals J. Agr. Food Chem. 2 1034 (1954)
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Ann. Chem. 656 135-140 (1962)
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-
24. Curham, W. F., J. F. Armstrong and G. E. Quinby, DDT and DDE Content
of Prepared Meals Arch. Env. Health 11 641-647 (1965)
25.
Hayes, W. J., G. E. QuPnby, K. C . Walker, J. W. E l l i o t t and W. M.
Upholt, Storage of DDT and DDE i n People with Different Degrees
of Exposure t o DMI A.M.A. Arch Industr. Health 18 398-406
(1958)
26.
Hayes, W. J., G. E. Quinby, K. C. Walker, J. W. E l l i o t t and W. M.
Upholt, A.M.A. Arch Industr. Health 18 398-406 (1958)
27.
Laug, E. P., Kunze, F. M., and P r i c k e t t , C . S.
Occup. Med. 3 245 (1951)
28.
Hayes, W. J., Ourham, W. F.,
(1956)
29.
Quinby, G. E.,
J.A.M.A.
30.
Davies, J. E., Welke, J. 0 . and Radomski, J. L. Report t o Am. Assoc.
I n d u s t r i a l Nurses 22nd Ann Meeting, Miami Beach, Apr. 1965.
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31. Hunter, C . G.,
(1963)
and Cueto, C . J.
A.M.A.
J.A.M.A.
Arch Ind. Hyg.
162
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890
Hayes, W. J., Armstrong, J. F. and Durham, W. F.,
191
- 175 (1965)
Robinson, J. and Richardson A.,
32. Maier-Bode, H., Angew. Chem. 71 188-189
33.
Hayes, W. J. and Dale, W. E.,
34.
Read, S. T. and McKinley, W. P.
-
B r i t . Med. J. 8 221-224
(1959)
Nature 199 1189-1191
(1963)
Arch. Env. Health 3 209-211
(1961)
212.
D i e Nahrung 6 48-56
35.
Danes, A.
36.
Quinby, G. E.,
J.A.M.A.
37.
Wasserman, M.
38.
Dale, W. E., Copeland, M. F., and Hayes, W. J., Chlorinated I n s e c t i c i d e s
33 471-477
i n t h e Body Fat of People i n India, B u l l . of WHO -
(1962)
Hayes, W. J., Armstrong, J. F. and Durham, W. F.
1 9 1 175 (1965)
- P r i v a t e Communication,
Sept. 1965.
(1965)
JAMES F. PRICE:
Thank you, D r . Bond.
I n discussing
t h i s , Bob S a f f l e d i d n ' t mention it b u t i n p u t t i n g t h i s t o p i c on
t h e program it was t o come under t h e commercial problem s e c t i o n .
The committee d i d n ' t intend t o imply that t h i s a r e a of p e s t i c i d e
residues i n meat w a s a commercial problem b u t we intended t o ask
these questions. What i s t h e incidence o r t h e problem of s u r v e i l lance i n t h e United S t a t e s ? I t h i n k l a t e r on i n t h e paper, which
I r e g r e t he d i d n ' t g e t t o , he mentioned some o f t h e differences
between countries i n t h e l e v e l s of some of these residues i n
meat products. So, we might a s k ourselves the question, if we
are going t o be faced with t h e problem of a n a l y s i s f o r p e s t i cides a r e we going t o be faced with something s i m i l a r t o t h e
cranberry s c a r e ? Certainly, t h e meat industry wishes t o avoid
t h i s . Perhaps we have time f o r one o r two questions, do we
have questions t o be d i r e c t e d t o D r . Bond? D r . S a f f l e .
DR. SAFFLE, Univ. of G a . : When you have a zero l e v e l ,
do you specify the method of a n a l y s i s ? I am p a r t i c u l a r l y int e r e s t e d from t h e standpoint of t h e work o f D r . Lisz, who gave
a more p r e c i s e method i n which he was picking up p a r t s p e r
b i l l i o n o r p e r t r i l l i o n of various p e s t i c i d e s . CO you specify
t h e m t h o d of analysis f o r zero tolerance?
DR. BOND: Let me say f i r s t o f a l l , i n t h e U. S.
Public Health Service we do not do any of t h i s s e t t i n g l e v e l s .
This i s a l l done by t h e Food and Drug Administration, an organi z a t i o n completely d i f f e r e n t from t h e one w i t h which I a m assoc i a t e d . The Food and Drug Administration, of course, has a bear
by t h e t a i l r i g h t now because of t h e recommendation t h a t was made
t o them a t t h e i r request by t h e National Research Council on t h i s
whole matter of zero tolerances. Some years ago before a n a l y t i c a l
procedures were accurate t o t h e degree t h a t they a r e now, the
allowable l i m i t was u s u a l l y s e t where it could not be detected.
But now a s methods g e t b e t t e r and b e t t e r , you can go down t o parts
p e r b i l l i o n and p a r t s p e r t r i l l i o n and even below t h a t i n some
cases, then you have t o decide a l e v e l t h a t i s allowable. The
Food and Drug Administration r i g h t now i s i n t h e furrows o f s e t t i n g allowable tolerances on many o f these p e s t i c i d e s down i n t h e
p a r t s p e r b i l l i o n l e v e l . Row j u s t t o do t h e s c i e n t i f i c work t o
213.
determine these p a r t s per b i l l i o n is going t o take, i n many cases,
y e a r s . J u s t t h e s e t t i n g up of t h e design of t h e experiment t o
guarantee t h a t t h e t o t a l environment f o r the experimental animals
i s indeed f r e e of t h e s u b j e c t p e s t i c i d e a t t h a t l e v e l i s a r a t h e r
f r i g h t e n i n g s i t u a t i o n . Say t h i s is a two-year feeding study,
any accident along t h e way can completely knock o u t your two-year
study and you have t o s t a r t over. The Food and Drug Administrat i o n i s well aware of a l l of the problems t h a t now f a c e them i n
having t o s e t allowable l e v e l s . Furthermore, they are q u i t e
aware of t h e f a c t that new a n a l y t i c a l procedures w i l l constantly
be developed which w i l l make it possible t o even go t o lower
l e v e l s , and t h e problem i s going t o g e t worse i n s t e a d of b e t t e r
a l l of the t i m e .
DR. PRICE: Thank you. If t h e r e a r e no more questions,
I w i l l turn t h i s back t o you, Bob.
DR. SAFFLE: Thank you, J i m . Our second t o p i c i s Experimental
Techniques f o r t h e Evaluation of Processing Equipment. I think i n the
processing a r e a up u n t i l t e n years ago we saw l i t t l e new machinery coming
on the market. However, t h i s has changed and i n t h e l a s t t e n years, part i c u l a r l y i n t h e l a s t f i v e years, we have seen a tremendous change i n new
machinery f o r processing; thus it becomes more important t o a l l of u s t o
have some method of evaluating t h e new machinery which i s coming on t h e
market. We asked Walter Urbain from Michigan S t a t e University t o cover
t h i s area and immediately following him R. B. S l e e t h of Armour and Company
w i l l handle t h e discussion period. Walter.
#####if#######