M. Wassermann

Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue

by M. WASSERMANN 1, D. P. NOGUEIRA 2, L. TOMATIS a, A. P. MIRRA, 4 H. SHIBATA 5, G. ARIE 8, SIMILICA CUCOS OE a n d DoRA WASSERMANN x i Department oJ Occupational Health, Hebrew University.Hadassah Medical School, Jerusalem, Israel ; 2 School oj Public Health, University oJ Sao Paulo, Brazil ; s lVorld Health Organization--Internationa1.4gency Jor Research on Cancer, Lyon, France; ~ Cancer Register of Sao Paulo, Brazil ; 5 Medico-Legal Institute of Sao Paulo, Brazil ; 8 In Memoriam Hospital A. C. Camargo, Foundation Antonio Prudente Sao Paulo, Brazil

Premature delivery and organochlorine compounds: polychlorinated biphenyls and some organochlorine insecticides.

Abstract Some organochlorine compounds (OCC), DDT and metabolites, γ-HCH, dieldrin, heptachlor epoxide and polychlorinated biphenyls were assessed in the serum of 17 women with premature delivery (PD) and 10 women with normal, third-trimester pregnancy. Out of 17 cases of PD, 8 cases were associated with high PCB serum levels (128.0 ppb versus 19.25 ppb in the control group), and 5 cases with high DDT serum levels (119.6 ppb versus 26.5 ppb in the control group). Two of the cases with high PCB serum levels also had high total DDT serum levels. The 5 cases with high total DDT serum levels also had high γ-HCH and heptachlor epoxide serum levels and 4 out of these 5 cases also had high dieldrin serum levels. The higher chlorinated PCB isomers constituted a higher percentage of total PCBs in the study group in comparison with the control group (about 30% versus 8.94%). At the same time, the percentage of total o,p ′-DDT was unusually high (50% of total DDT in the study group versus 30% in the control group[tiThe possible role of the relatively high serum levels of the organochlorine compounds assessed in this study, in the occurrence of PD, is discussed.

Organochlorine compounds in mother and fetus during labor

Abstract Some features of the storage of organochlorine compounds in mother and fetus as assessed during labor are reported in this paper. Organochlorine insecticides (DDT and metabolites, dieldrin, y-BHC, and heptachlor expoxide) and polychlorinated biphenyls were assessed in maternal adipose tissue, maternal blood, fetal blood, maternal uterine muscle, placenta, and amniotic fluid. The concentration of total DDT, y-BHC, and PCBs was greater in extracted lipids of fetal blood than in maternal blood and still higher in the uterine muscle. The concentration of dieldrin and heptachlor expoxide was higher in extracted lipids of fetal blood and placenta than in maternal blood and uterine muscle. The metabolites of DDT were found in different ratios in mother and fetus. The ratios for individual polychlorinated biphenyl compounds were similar for maternal and fetal plasma on the one hand and placenta and uterine muscle on the other. These facts suggest quantitative differences in the ability of these tissues to metabolize and/or store organochlorine compounds. These data emphasize the importance of the maternal organism in protection of the fetus against environmental hazards.

EFFECTS OF ORGANOCHLORINE INSECTICIDES ON BODY DEFENSE SYSTEMS

The study of the biological effects of organochlorine insecticides has revealed numerous experimental (Cueto & Brown, 1958 a. b; Falk ef ul., 1965; Gerebzoff el al., 1950; Hart & Fouts, 1963, 1965; Juchau et al., 1966; Nelson & Woodard, 1949; Ortega e ta! . . 1956; Straw et al., 1965; Vilar & Tullner, 1959) and clinical data (Geyer, 1962; SQnchez-Medal et ul., 1963; Weisenfeld et al., 1964), many of them in accordance with one another and others apparently contradictory. If the opinions regarding the acute effects are generally agreed on, the effects of chronic exposure to small amounts of insecticides still remain vaguely outlined. We consider that the often contradictory biological effects of these substances, which represent consistently encountered constituents of the animal body in our times (Wassermann et al., 1966 a, b) should be dynamically investigated by placing the organism in circumstances requiring defense to various environmental conditions. Studies on the following topics were carried out:

Immunological and detoxication interaction in p,p-DDT fed rabbits

SummaryThirty-one rabbits were immunized against Salmonella or SRBC. These rabbits had an impaired immunological response when they received 200 ppm p,p′-DDT in their drinking water during a period of 38 days. The total gamma globulins as reflected by the 7 S fraction were significantly decreased in the p,p′-DDT-Salmonella receiving rabbits when compared with the rabbits receiving only Salmonella. This decrease was not statistically significant in the p,p′-DDT-SRBC receiving rabbits when compared with the rabbits receiving only SRBC.The antibody titer against Salmonella was significantly decreased in p,p′-DDT-Salmonella receiving rabbits when compared with the rabbits receiving only Salmonella. The decrease of the SRBC antibody titer in the p,p′-DDT-SRBC receiving rabbits was not statistically significant.The plasma total DDT level differed significantly in the two groups receiving p,p′-DDT (p,p′-DDT-Salmonella and p,p′-DDT-SRBC receiving rabbits). This finding may explain the different degree of impairment of the immunological response, the higher plasma DDT level having a more marked effect. These differences in total DDT plasma level in the two groups of rabbits which received the same amount of p,p′-DDT in their drinking water may be considered as a consequence of the concomitant presence of a different kind of foreign antigen in the internal milieu.The bi-directional relationship between a detoxication process and an immunological response is emphasized.

Function of adrenal gland-zona fasciculata in rats receiving polychlorinated biphenyls.

Abstract The corticosterone plasma level and the storage of organochlorine compounds (OCC) were assessed in mature male rats receiving 250 ppm polychlorinated biphenyls (PCBs)-1221 for 10 wk. The storage of PCBs in the adipose tissue of rats which received 250 ppm PCBs-1221 reached a level of 5.8 ppm as against 0.065 ppm in controls. Organochlorine insecticide storage was also increased in rats receiving PCBs-1221 (0.65 ppm DDT as against 0.29 ppm in controls and 0.15 ppm Dieldrin as against 0.02 ppm in controls) although they did not receive extra amounts of these OCI except the amount currently present in food and water. These data confirm some of our previous findings, i.e., the presence in the animal body of a larger quantity of an organochlorine compound may influence the metabolic clearance rate of other organochlorine compounds. The mean level of corticosterone in these rats was 12.3 μg/100 ml as against 6.2 μg/100 ml in control rats. The difference between the two groups was statistically significant (P These findings comply with morphological features of hyperfunction of the adrenal zona fasciculata in rats receiving PCBs-1221 which we described in a previous study. The results are interpreted as evidence of the need for a higher level of glucosteroids in defense against the stressor character of PCBs-1221 and perhaps also of the need for catatoxic activity of glucosteroids.

Effects of Pregnancy on Storage of Organochlorine Insecticides

This paper reports on the concentration of or-ganochlorine insecticides in the tissues of 35 pregnant women, 33 nonpregnant women in the fertile period of life, and 23 neonates. In pregnant women, fat tissue, placenta, uterus, and blood were examined; in nonpregnant women, fat tissue only was analyzed; and in neonates, the umbilical blood. All the samples were analyzed by gas liquid chromatography. The findings of this study indicate that in pregnancy a lower storage of the following organo-chlorine insecticides occurs in the adipose tissue: p,p′-DDT, p,p′-DDD, o,p′-DDT + o,p′-DDD, o,p′-DDE, and total o,p′-DDT. The same phenomenon is observed for BHC isomers and dieldrin. All the organochlorine insecticides found in the fat tissue of pregnant women were present both in maternal and fetal blood in all the cases studied. These findings suggest that in pregnancy the metabolism of organochlorine insecticides is enhanced, and that organochlorine insecticides pass the placental barrier.

ORGANOCHLORINE COMPOUNDS IN THE GENERAL POPULATION OF THE SEVENTIES AND SOME OF THEIR BIOLOGICAL EFFECTS (IN MAN AND ANIMALS)

ABSTRACT The interaction of an organism and its environment is determined, to a significant degree, by the composition of the environment and the biochemical individuality of the given organism. A characteristic of the living organism is to carry the foreign compounds which enter them through continuous cycles of activity like their own constituents. Some of the compounds of the environment accumulate to some extent in the animal body. This storage constitutes a dynamic process. At a certain storage level, effects on the metabolism of normal constituents of the animal body, on the genetical make-up, and on its defence mechanisms (detoxication processes, neuro-endocrine, and immunologic processes) are observed. This paper reports on the size of Organochlorine Insecticides and Poly-chlorinated Biphenyls storage in the human general population in the seventies and some of the biological effects of these compounds on humans and experimental animals.

The effect of organochlorine insecticides on serum cholesterol level in people occupationally exposed

SummarySerum cholesterol was determined in 206 workers occupationally exposed to organochlorine insecticides (OCI) and in 86 workers non-occupationally exposed to these chemicals.In both groups of workers the serum cholesterol level increased with age. The increase was greater in exposed workers but the difference between the two groups was statistically significant only in the over 45 years age group.It is thought that OCI induce an increase of cholesterol synthesis, but this process is masked by a concomitant breakdown. In the over 45 years age group a diminished reactivity of homeostatic processes may explain the finding of enhanced cholesterol synthesis which is no longer masked by concomitant catabolism.

Epidemiology of mesothelioma in Israel.

Abstract During the period 1960–1972, 65 cases of mesothelioma were registered at the Israel Cancer Registry. In 13 cases the histologic diagnosis was not considered as definite and they were, therefore, excluded. A review of the medical and occupational histories where available of the remaining 52 cases reported. The diagnosis was made by biopsy in 34 cases (65%) and by autopsy in 18 cases (35%). Twenty-seven cases (52%) were located in the pleura and 25 (48%) in the peritoneum. There were 30 males (58%) and 22 females (42%). The age at diagnosis ranged from 1.5 to 85 years and the highest age-specific rate (5.0/million) corresponded to the age group 60–74 years. The average annual incidence rate for the total population was 1.5 cases per million. Distribution by country of origin showed that Jews born in Europe or America had the highest incidence rate (3.4/million) and the lowest rate (0.6/million) was found among Jews born in Israel. The age-standardized rates indicated that these differences were due to a dissimilar age distribution among the country of origin groups. Only one case had a definite occupational history of exposure to asbestos. It is suggested that, in addition to occupational exposure other etiological factors may play an important role in the epidemiology of mesothelioma in Israel.