Three generations affected by one DDT exposure

DDT (dichlorodiphenyltrichloroethane) a weed killer long recognized as a health threat to the human endocrine system — banned in 1972 — is still carried in third and sometimes fourth generation exposed descendants.

During her presentation at the Endocrine Society annual meeting in Boston, Massachusetts, Dr. Cohn discussed some of the ways the CHDS is using multiple generations of data. Her talk: “ Endocrine Genetic and Epigenetic Control of Development: Bases for Human Health and Disease” was given on Sunday morning at EMBO 2016.

The original cohort — or cluster of people studied — was approximately 20,000 pregnant patients at the Kaiser Permanente Medical Group in Northern California. Successive generations of researchers have followed that original group, their children, grandchildren, and great-grandchildren. CHDS has data on each pregnancy, health records for the six months prior to pregnancy for each woman in the original group, as well as data collected during well baby and acute medical visits and exams at age five, nine to eleven, 15 to 17, 33, 44, and 50. Similar data is still being collected for individuals in successive generations, but current research focuses on the F1 cohort, the first generation offspring.

Of the 65,000 serum samples taken from 1960 to the present, the most striking initial finding was the ubiquitous presence of DDT in the 20,000 pregnant women studied.

DDT was banned in the United States in 1972.

Barbara A. Cohn: “There are NO women in the F0 cohort [1960] who do not show exposure to DDT in blood samples. There are actually three different DDT exposures: the insecticide itself, its metabolites, and its contaminants. What we found is that impact varies by type of exposure, (insecticide, metabolite, or contaminant), and by timing of exposure, gestational, peripubertal, or during pregnancy.”

Each of three forms of DDT is identified as an endocrine disruptor in animal studies. Earlier studies of women in the F0 cohort (1960) found similar evidence of endocrine disruption for years following DDT being banned. Exposure waned as the insecticide, its metabolites, and contaminants began to degrade. But more recent studies have identified links to breast cancer, reduced fertility, testicular cancer, increased breast density, DNA methylation (modification in DNA activity), and hypertension in children born to the original cohort.

“The F1s are a spectacular midlife cohort,” Dr. Cohn said. “What makes them so spectacular is that we have in utero data on each of them as well as complete medical histories.”

The odds ratio for breast cancer in the original (F0) cohort and in their offspring (F1) is linked to the timing of each groups' exposure.

Women exposed at four years of age or younger had up to a 12-fold increase in risk for breast cancer. Risk decreased with increasing age at exposure, but never disappears.

F1 generation women with only in-utero DDT exposure still had up to a four-fold increased risk for breast cancer. Increasing in-utero exposure is also associated with increased risk for higher breast tissue density.

The effect of time on pregnancy in the F1 generation varied by the type of exposure. In-utero exposure to DDT itself increased fecundity, Dr. Cohn reported. But exposure to DDE, a persistent metabolite of DDT, reduced fecundity and increased time to becomming pregnant.

Higher exposure to DDT and its metabolites increased the risk for testicular cancer in male offspring, she also found. While greater exposure to DDT and metabolites increased the risk of hypertension in both male and female offspring by their age of 50.

“We are finding and exploring multiple pathways by which DDT might exert its disruptive action. What we know is that different forms of DDT affect different metabolic pathways and all of them seem to affect lipid metabolism. Animal testing is helping determine the mechanisms involved.”

Barbara A. Cohn PhD

lipids are molecules that contain hydrocarbons and make up the building blocks of the structure and function of living cells. Examples: fats, waxes, sterols, fat-soluble vitamins (such as A, D, E, and K), monoglycerides, diglycerides, triglycerides, phospholipids, and more. The main biological function of lipids includes storing energy, signaling, and being components of cell membranes.

Talk Description:
New discoveries of multigenerational health consequences of developmental exposure to endocrine disrupting chemicals will be reviewed. Consequences for reproduction, neurodevelopment, metabolic disorders, cardiovascular disease and cancer will be addressed. The significance of these new findings for the future of biomedical research, public health prevention and social policy will be discussed.

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This DDT powder contained 50% Dichloro Diphenyl Trichloroethane (DDT)
Note: "Use on potatoes, peas, corn and ornamentals" circa early 1960s.
Image Credit: Wikipedia