TOXICOLOGY OF ORGANOCHLORINE INSECTICIDES significantly higher than in the population protected by the spraying. Although

54 TOXICOLOGY OF ORGANOCHLORINE INSECTICIDES significantly higher than in the population protected by the spraying. Although

serum -gammaglutamyl transpeptidase was not statistically different from con- trols the mean in applicators was greater than the maximum laboratory mean level and alanine aminotransferase values were significantly greater in the applicators although not deemed clinically significant and possibly associated with alcohol consumption (Bouwman et al., 1991a, 1991b). Members of households that had been sprayed inside with DDT had significantly greater levels in their serum than people from non-sprayed households. Recent findings from studies in Costa Rica have linked declines in neurobehavioural functioning and an increase in neuro- psychological and psychiatric symptoms with DDT exposure of retired malarial sprayers, but no clinical differences were detected (Van Wendel de Joode et al., 2001). A possible association between maternal blood DDE levels and pre-term and small birth weight for babies has been proposed recently (Longnecker et al., 2001).

No significant overall cause of specific mortality excess among men potentially exposed at work to DDT from 1935 to 1976 was detected (Wong et al., 1984) and similarly, a population living downstream from a defunct DDT manufacturing plant showed no DDT-specific illnesses or ill health, but possibly some changes in clinical chemistry, despite total DDT serum levels three times the national mean (Kreiss et al., 1981). The induction by DDT level of microsomal enzymes of human liver was demonstrated first in workers and DDT may be more important than DDE in this regard (Poland et al., 1970).

Evidence regarding mutagenic activity of DDT and its significance in humans is uncertain (Smith, 2001). Although there is a lot of evidence against DDT causing liver cancer in humans in Western countries, there is still the possibility of it acting as a promoter of potent carcinogens such as aflatoxin. Many studies have deter- mined DDT levels in cases of cancer or other diseases but it is difficult to judge the significance of these (Cocco, Kazerouni, and Zahm, 2000; Smith, 2001; Snedeker, 2001; Turusov, Rakitsky, and Tomatis, 2002). A study of deaths that occurred among men who used DDT in an antimalarial campaign in Sardinia in the late 1940s showed that workers had a significant increased risk for liver and biliary tract cancers and multiple myeloma. However, non-exposed workers also showed ele- vated incidences of cancer (Cocco et al., 1997).

There have been reports that pancreatic cancer might be associated with exposure to DDT and ethylan in a nested case–control mortality study among workers at a chemical plant followed by interviews with next of kin and co-workers and exam- ination of work records (Garabrant, Held, and Homa, 1993; Garabrant et al., 1992; Malats, Real, and Porta, 1993). However, this has not been confirmed in wider non- occupational surveys (Cocco, Kazerouni, and Zahm, 2000).

Plasma and tissue levels of DDT have been particularly targeted as being linked with a rising incidence of breast cancer (Dewailly, Ayotte, and Dodin, 1997; Dewailly et al., 1994a, 1994b; Wolff et al., 1993). Much of the evidence has been reviewed in detail and is not supportive or is inconclusive (Ahlborg et al.,

55 1995; Cocco, Kazerouni, and Zahm, 2000; Key and Reeves, 1994; Snedeker,

DDT

2001; Wolff et al., 2000a, 2000b). Elevated levels of DDT or DDE were reported in cancerous breast tissue fat compared with tissue from benign mammary disease (Guttes et al., 1998). In contrast, a number of studies have found no relationship between blood levels of DDE and risk of, or progression of, breast cancer (Hunter et al. , 1997; Schecter et al., 1997; Snedeker, 2001). The study of Schecter et al. (1997) is of particular interest in that women in North Vietnam were examined who had generally high levels of DDT or DDE due to exposure from antimalarial use.

Levels in fat, blood, and milk The highest reported storage of DDT and related compounds was that of a healthy

worker whose fat contained DDT and DDE at concentrations of 648 and 483 ppm respectively, but most have been considerably lower (Smith, 1991, 2001). An im- portant point is that it has always been difficult to assess exposure. Considerable evidence suggests that with time the greatest proportion of DDT in people is as the metabolite DDE (Smith, 1991). Although each person without special exposure to DDT has relatively constant serum levels of DDT and DDE, DDE values differ more than the DDT values from person to person. Levels of DDT and its metabo- lites in the serum of adults rose over a 12-month period following application of the pesticide to their homes in KwaZulu, South Africa. In contrast, levels fell in the age group 3–20 years, showing the complexity of any pharmacokinetic interpretations (Bouwman, Becker, and Schutte, 1994). Surveys have demonstrated a gradual decline in the concentrations of DDT and related compounds in human fat (Smith, 1991; Snedeker, 2001; Turusov, Rakitsky, and Tomatis, 2002). Presumably

a similar decline has occurred in the levels of these compounds in human serum. Consumption of fish appeared to be a predictor of plasma DDE levels but most reliable were age and serum cholesterol (Laden et al., 1999).