Blood levels of organochlorine pesticides in Argentina: Occupationally and nonoccupationally exposed adults, children and newborn infants

TOXICOLOGY

AND

APPLIED

Blood Levels Occupationally

20, 186-193

PHARMACOLOGY

(1971)

of Organochlorine Pesticides in Argentina: and Nonoccupationally Exposed Adults, Children and Newborn Infants1

JACK L. RADOMSKI, EMILIO ASTOLFI*, WM. B. DEICHMANN, AND ALBERTO A. REY Department

of Pharmacology University of Miami, *Far&tad de Universidad

and the Research and Teaching Center of Toxicology, School of Medicine, Miami, Florida, and the Medicina, Universidad de1 Salvador y National de Buenos Aires, Argentina

Received

November

30, 1970

Blood Levels of Organochlorine Pesticides in Argentina: Occupationally and Nonoccupationally Exposed Adults, Children, and Newborn Infants. RADOMSKI, JACK L., ASTOLFI, EMILIO, DEICHMANN, WM. B., and REY, ALBERTO A. (1971).Toxicol. Appl. Pharmacol. 20, 186-193.Determination of the concentration of organochlorinepesticideshasbeenmadein adults, children, newborn infants, and various groups of occupationally exposed individualsin Argentina. /%HCH levelsin adultsin Argentina areapproximately 16 timeshigher, on the average,than the levelsof /%HCH found in the U.S. In contrast, the concentrations of p,p’-DDE, dieldrin, and p,p’-DDT arecloselysimilarto thosein the U.S. Concentrationsof B-HCH in children in Argentina are lower, but still higher than in adults in the U.S., and much higher than in U.S. children. Pesticidelevels in workers handling HCH were extremely high, as were the levels of DDT and isomersin thoseoccupationally exposedto this pesticide.No dieldrin was detectedin theseworkers-a possibleindication that microsomalstimulation by DDT may have beenresponsiblefor clearing the tissues. The DDE:DDT ratio appearedto be an accurate measurementof a recent exposure to DDT. Pesticidespassedthe placental barrier, but transmissionwas apparently somewhatretarded. Concentrationsof p,p’DDE,p,p’-DDT, dieldrin, and /%HCH in the newbornwereapproximately 40% of the pesticideconcentration in the blood of the mother. This percentagewas higher for c+HCH, and lindane. In recent years new, highly sensitive, and rapid techniques for measuring chlorinated hydrocarbon pesticide levels in the blood have been developed. Studies involving the blood concentrations of these substanceshave been conducted in certain European countries and in the United States. Becauseregulatory controls governing the usage of pesticides in South American countries are frequently lessrigid and lesseffective than those in the U.S. and European countries, there is someconcern as to the possible health hazards that may result from the excessive pesticide exposure of these Latin populations. This possibility led to the initiation of an investigation of pesticide blood 1This investigationwassupportedby Public Health ServiceGrant No. 5 PO1ES 0005244,05, and06. 186

ORGANOCHLORINE

PESTICIDE

HUMAN

BLOOD

LEVELS

187

levels of various groups of individuals in 3 areas of Argentina: (1) In Catamarca Province, 3 groups were studied : (a) a group of individuals involved in administrative work (with no occupational pesticide exposure), representative of the general adult population; (b) workers occupationally exposed to hexachlorocyclohexane for at least the past 5 yr; (c) ex-pesticide workers, who had used DDT in a malaria control program, but who had not handled this pesticide occupationally for at least 5 yr. (2) In Salta Province, 3 groups were studied: (a) nonoccupationally exposed administrative workers; (b) workers occupationally exposed to hexachlorocyclohexane for at least 5 yr (similar to the group in Catamarca Province); (c) workers occupationally using DDT in a malaria control program for at least the past 5 yr. (3) In Ciudadela, blood samples were taken from 3 groups : (a) children ranging in age from 1 to 10 yr; (b) a series of mothers from whom blood samples were taken immediately following delivery and whose pesticide levels were compared with those found in the blood of(c) their newborn infants. METHODS

Procedures Blood was drawn utilizing vacutainers containing sodium oxalate and packed in dry ice for shipment by air express to Miami, Florida. It should be noted, however, that while the sampleswere not decomposed upon arrival, considerable hemolysis had occurred in transit. The analyseswere carried out by a gas chromatographic procedure utilizing the electron capture detector (Radomski and Rey, 1969, 1970). It constitutes a simplification and modification of the procedure of Dale et al. (1966). In comparative study of the pesticide concentrations of the mothers and their newborn infants, the blood was drawn from the mother as promptly as was feasible after the delivery and from the umbilical cord of the infant immediately after birth. CaseSelection From Catamarca Province. (a) A group (9 female, 1 male) of white administrative workers (secretaries, typists, nurses) who had no occupational exposure to any pesticide. Ages ranged from 25 to 58, heights from 1.50 to 1.70 m, weights from 58.5 to 88 kg. (b) A group (10 male) of white pesticide workers (sprayers, spray truck drivers, supervisors)all of whom were currently involved in the spraying of crude HCH and who had been so occupationally employed for 5 yr or more. All admitted to the extensive private use of this pesticide in their own homes and gardens. Ages ranged from 39 to 56, heights from 1.66 to 1.83 m, weights from 64 to 91 kg. (c) A group (10 male) of white former pesticide workers (formerly employed assprayers in a malaria control program) who had not used pesticides occupationally for at least the past 5 yr. They were currently employed as maintenance workers and parking attendants. None admitted to the personal use of pesticidesin the home. Ages ranged from 44 to 55, heights from 1.52 to 1.82 m, weights from 64 to 106 kg. From Salta Province. (a) A group (3 female, 7 male) of white administrative workers, maintenance workers, laboratory technicians, secretaries and office boys with no occupational exposure to pesticides. Ages ranged from 21 to 35, heights from 1.55 to 1.71 m, weights from 51 to 70 kg. None admitted to the home use of pesticides. (b) A group (10 male) of white pesticide workers, sprayers, and their supervisorsall of whom

188

RADOMSKI

ET AL.

were currently using crude HCH and had been so employed for 5 yr or more. None admitted to the home use of pesticides. Ages ranged from 27 to 40, heights from 1.65 to 1.87 m, weights from 60 to 90 kg. (c) A group (10 male) of white workers currently employed in the malaria control program spraying DDT. All have been so employed for the last 5 yr or longer. None admitted to the home use of pesticides. Ages ranged from 29 to 48, heights from 1.45 to 1.78 m, weights from 53 to 91 kg. The children selected for this study were 1 to 10 yr of age, white, and equally divided as to sex. None had any out-of-the-ordinary recognized exposure to pesticides in the home or otherwise. The mothers selected were 19 to 34 yr of age, employed as domestics, white, and admitted to no out-of-the-ordinary pesticide exposure. RESULTS

Pesticide Blood Levels in Nonoccupationally Exposed Adults and Children The most striking observation immediately apparent from our data was the markedly elevated levels of the isomers of hexachlorocyclohexane, particularly the p-isomer, found in both children and adults (Table 1). In the U.S. we found a mean of 1.40 pg/l (ppb) in the 26 adults (males and females) studied. In a comparable group of adults from the 2 provinces of Argentina, Salta and Catamarca, a mean of 23.01 pg/l (ppb) of the &isomer was found. In the U.S. it is rare to detect y-HCH (Lindane) in either adults or children, whereas, an average level of close to 1 pg/l was observed in the adults of Argentina. In contrast, however, concentrations of dieldrin, p,p’-DDE, and p,p’-DDT were very similar to those observed in the U.S. 1

TABLE PESTICIDE

CONCENTRATIONS NONOCCUPATIONALLY

Subjects United States Adults

[pg/l (ppb) &SD] EXPOSED

No. of subjects &HCH 26

1.40

IN POPULATION

Lindane (y-HCH)

20

Children 5-10 yr

18

Children l-5 yr

19

23.01 It10.14

6.61 13.93 6.72 rk6.57

OF MEMBERS AND U.S.A.

OF

THE

Dieldrin

p,p’-DDE

p,p’-DDT

0

1.49 rtl .oo

15.72 16.51 __.--

4.18 11.83

0.98 *1.16

1.43 -cl.21

14.53 &6.76

3.18 1-1.70

0.43 xko.34 0.32 10.24

0.94 zkO.92

8.13 &4.06 5.56 14.83

4.21 -1.41

50.46

Argentina Adults

WHOLE BLEND IN ARGENTINA

0.54 10.29

2.49 +2.26

Pesticide Levels in the Newborn In order to investigate the extent of transport across the placental barrier of the various pesticidespresent in human blood, 13mothers and their newborn were selected

ORGANOCHLORINE

PESTICIDE

HUMAN

BLOOD

LEVELS

189

190

RADOMSKI

ET AL.

for study. Mean pesticide blood concentrations obtained in these mothers were closely similar to those obtained from the general population in Argentina. Blood levels in the newborn were lower for each pesticide (Table 2) except in a few instances. The ratio of pesticide blood concentration in the blood of the newborn infant to the mother was computed for each pesticide. With /I-HCH, dieldrin, p,p’-DDE, and p,p’-DDT, ratios were closely similar: 0.44,0.44,0.39, and 0.41, respectively. With c(-HCH the ratio was 0.84. The ratio for lindane was even higher (0.73). However, this ratio was based on relatively few measurements, since only zero or trace amounts of lindane were found in many of the newborn. The DDE-DDT ratio was computed for all mothers and newborn infants. This ratio did not differ significantly in the newborn as compared to the mother. Pesticide Concentrations

in the Occupationally

Exposed

Pesticide concentrations were measured in pesticide workers using, or having used in the past, either hexachlorocyclohexane or DDT. This experiment was carried out in two provinces of Argentina-Catamarca and Salta. Blood levels obtained from these occupationally exposed individuals were compared with administrative workers, in each province, who had no occupational exposure. In Catamarca Province, pesticide workers currently using crude hexachlorocyclohexane had remarkably high blood levels of both P-HCH and y-HCH (Table 3). On the other hand, the blood concentrations of dieldrin, p,p’-DDE, and p,p’-DDT in these men were normal. However, pesticide workers who had formerly used DDT in the malaria control program, but who had not worked with pesticides for 5 yr or more, had approximately 5 times as much blood DDE and approximately 3 times as much DDT as normal. The dieldrin levels were essentially normal; however, the levels of y-HCH, while much lower than in the pesticide workers who were currently using this material, were approximately 2.5 times the normal. In Salta Province, the blood concentrations of pesticides in the nonoccupationally exposed administrative workers were essentially the same as the similar group in Catamarca Province. Pesticide workers who were currently using hexachlorocyclohexane had levels of /3-HCH almost as high as the similar group in Catamarca Province, but a much lower although still elevated level of the y-isomer. The fourth group of the occupationally exposed have been working with DDT in the malaria control program in Salta Province for 5 yr. This group had remarkably high blood levels ofp,p’-DDE andp,p’-DDT, while their levels of dieldrin, /L?-HCH, and lindane were essentially normal, or perhaps somewhat lower than normal. Comparison of the DDE:DDT ratio of some of these groups is interesting. This ratio in the group of pesticide workers from Salta Province who were currently working with DDT was 1.08 ; in workers from Catamarca Province who had worked occupationally with DDT, but were not currently doing so, this ratio was 7.62. In the nonoccupationally exposed, the ratio is commonly approximately 4. These observations are consistent with the premise that DDE is a relatively stable, long-lived metabolite of DDT in fat, and the blood DDE: DDT ratio is a measurement of the recency of the exposure to DDT. A similar relationship seems to exist between the /?-isomer of hexachlorocyclohexane and the y-isomer. In workers in Catamarca Province currently using crude HCH, the ratio of /3 to y was 11.3 for the administrative personnel (nonoccupationally exposed), and 3.4 for the occupationally exposed. However, the

TABLE

3

9

10

10

10

10

10

0.51 10.65

3.47 zt2.99

0.25 +0.25

0

70.38 f67.73

1.71 .I.26

Lindane b-H=0

13.65 120.06

182.33 1107.21

26.66 -+I].19

50.53 zt27.51

237.70 k139.92

19.35 17.88

p-HCH

& SD] IN WHOLE BLEND IN OCCUPATIONALLY EXPOSED PEOPLE IN ARGENTINA

No. .--~-.------

(ppb)

0

1.16 kO.72

0.77 hO.74

2.81 It3.59

1tO.60

1.09

2.09 11.25

Dieldrin

AND

’ Workers who have been using HCH for 5 yr or more. * Former malaria-control personnel who previously used DDT but have not worked with it for 5 yr or more ’ Pesticide workers who have been working with DDT for 5 yr or more (malaria-control program).

M

Pesticide workers’

M, F M

personnel

Pesticide workers”

Salta Province Administrative

M

Ex-pesticide

workersb

M

Pesticide worker@

M,F

Catamarca Province Administrative personnel

[&I

Sex

CONCENI.RATIONS

Subjects

PESTICIDE

363.00 k367.78

17.01 18.88

13.30 Xt3.64

86.11 zt44.32

14.49 16.43

15.78 h8.94

p,p’-DDE

NONOCCUPATIONALLY

346.36 5348.39

2.31 ztl.93

2.47 11.70

11.28 rt5.41

3.86 10.90

3.88 zt1.64

p,p’-DDT

192

RADOMSKI

ET

AL.

occupationally exposed workers who were using HCH in Catamarca Province did not have as much y-isomer in their body relative to /3 as those in Salta Province. DISCUSSION It is apparent from these results that a potential health hazard exists for people of all ages in Argentina related to the promiscuous use of crude hexachlorocyclohexane. Mean levels of the @-isomer, chronically the most toxic in the blood of adults, were 16 times higher than those found in the U.S., where crude HCH is not permitted to be used on foodstuffs and is not commonly used as a household pesticide. Similar blood levels have been found in Asiatics, principally the Japanese and Formosans (Radomski et al., 1971). Results obtained from blood samples of Formosans and Japanese who have left their islands and come to the U.S. for scientific study indicate that /3-HCH levels are remarkably persistent, for although the levels in these individuals were lower than the general population of the area from which they came, they persisted to a markedly elevated degree for 2-5 yr after the apparent cessation of exposure. Elevated blood levels of the HCH isomers were present also in children and in newborn infants in Argentina, although to a lesser extent. Conversely, the levels of dieldrin and DDT and its metabolites in all individuals in Argentina-children, adults and newborn-not occupationally exposed, were quite comparable to those found in the U.S. Most pesticide levels in the newborn were approximately 407” of those found in the mother, demonstrating conclusively that pesticides do cross the placental barrier (although apparently there is some protection). Rather remarkable results were obtained in the study of pesticide levels of the occupationally exposed in Argentina. In every case these levels reflected with remarkable accuracy of the various groups. Where DDT was in current use by these workers, remarkably high blood levels of DDE and DDT were observed. When the use had been discontinued 5 yr previously, lower but still elevated levels, particularly of DDE, were observed. Workers using crude HCH had tremendously elevated levels of both y and /l isomer. However, these workers had perfectly normal levels of DDT and isomers, as well as of dieldrin. These results substantiate the premise that &-DDE is the storage isomer of DDT and is rather persistent. It is apparent that the DDE: DDT ratio is a reflection of the recency of exposure to DDT. All these observations confirm the concept that pesticide blood measurements are an accurate index of the pesticide body burden and the exposure to pesticides, and provide an easily utilized and extremely valuable technique for the study of the effects of pesticides in man. Obviously, these individuals in Argentina who have such markedly elevated levels of the isomer of HCH would provide a rich source for human studies of the effects of chronic exposure to these substances. The chronic toxicity of the isomers of HCH in rats have been investigated by Fitzhugh et al. (1950). /%HCH was the most toxic, producing retardation of growth at feed concentrations as low as 100 ppm. This isomer, also produced a moderate degree of liver damage at 100 ppm and detectable liver changes at 10 ppm. Significant liver enlargement was also produced at the 10 ppm feed concentration. The tissue distribution and accumulation of the isomers of HCH was investigated by Davidow and Frawley (1951) in the rat and dog. At

ORGANOCHLORINE

PESTICIDE

HUMAN

BLOOD

LEVELS

193

feed concentrations of 100 ppm, the p-isomers accumulated in the fat to the greatest extent (an average concentration of 2000 ppm). Feeding the same concentration of the cc-isomer produced fat concentrations in a range of 100-400 ppm and the y and 6 isomers, yet produced lower fat concentrations. When feeding was discontinued, the p-isomer was also the most persistent. If one extrapolates from the above results on the basis of the minimal chronic toxic dose of 10 ppm in the diet, one might estimate that one might find about 100 pg/g (ppm) in the fat or 300 pg/l (ppb) in the blood of humans suffering a similar degree of exposure. While such extrapolations are subject to considerable error, it seems that the concentrations of /3-HCH observed in the occupationally exposed are in the range of what might be associated with liver toxicity. It is interesting that we were unable to detect levels of dieldrin in pesticide workers who were working with DDT and had extremely high levels of DDT and DDE. Animal data (for rats) has suggested that the administration of DDT decreases the storage level of dieldrin, perhaps by microsomal stimulation. Our observation would tend to extend this hypothesis to humans. REFERENCES W. E., CURLEY, A., and CUETO, C. (1966). Hexane-extractable chlorinated insecticides in human blood. Life Sci. 5, 47. DAVIDOW, B., and FRAWLEY, J. P. (1951).Tissuedistribution, accumulationand elimination of the isomersof benzenehexachloride(18631).Sot. Exp. Biol. Med. 76, 780-783. FITZHUGH, 0. G., NELSON, A. A., and FRAWLEY, J. P. (1950). The chronic toxicities of technical benzenehexachloride and its alpha, beta and gammaisomers.J. Pharm. Exp. Ther. 100, 59-66. RADOMSKI, J. L., and REY, A. (1969).Determination of chlorinatedhydrocarbon pesticidesin humanand animaltissues.II. Blood, Brain, Liver, Kidney, Gonad and Fat. Znd. Med. Surg. DALE,

38, 53-59.

J. L., and REY, A. (1970). The electron capture detector in the analysis of chlorinated hydrocarbon pesticidesin tissueswith and without clean-up.J. Chromatogr. Sci. 8, 108-I 14. RADOMSKI, J. L., DEICHMANN, W. B., REY, A. A., and MERKIN, T. (1971). Human pesticideblood levelsas a measureof body burden and pesticideexposure.Toxicol. Appl. Pharmacol. 20, 175-185.

RADOMSKI,