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Multiple Studies Links Pesticide Exposure to Altered Cytokine Expression and Non-Hodgkin’s Lymphoma

The Pesticide Chlordane is Implicated

Scientists have documented the dangers of in utero pesticide exposure for many years. A study published in 2011 outlined specific risks from fetal exposure to two specific pesticides.

Researchers with the National Cancer Institute, Johns Hopkins Bloomberg School of Public Health, Emory University, Johns Hopkins School of Medicine and Arizona State University found a connection between fetal exposure to chlordane and permethrin and potentially harmful inflammatory cytokine levels.

The study, “Fetal exposure to chlordane and permethrin mixtures related to inflammatory cytokines and birth outcomes (Neta),” examined umbilical cord serum to find what effects pesticide exposure could have on inflammatory cytokines. They also looked for effects on birth size, head circumference, body fat to length ratio and gestational age.

The Neta researchers collected umbilical cord serum specimens from 341 babies born at Johns Hopkins Hospital. Scientists successfully analyzed 297 samples for chlordane-based pesticides and 185 for permethrin pesticides. The scientists took into account the mother’s age, race, body mass index, maternal medical history and smoking status when determining those pesticides’ potential effects on birth metrics.

The scientists found trans-nonachlor, a chlordane isomer in 93% of the serum samples, and the chlordane metabolite oxychlordane in 84% of the serum samples. They also found permethrin isomers trans-permethrin and cis-permethrin in 52% and 41% of the samples respectively.

The Neta researchers found chlordane and permethrin concentrations may be associated with altered specific inflammatory cytokine levels, as well as lower birth weight.

Inflammatory cytokines are signaling molecules which regulate the body’s inflammation response. They are divided into two broad categories: proinflammatory cytokines which encourage inflammation, and anti-inflammatory cytokines, which mitigate it. When working together, they ensure the body inflammation processes serve their purpose and respond correctly to injury or infection. When thrown out of balance, inflammation can become chronic and cause myriad health problems ranging from rheumatoid arthritis and bowel diseases to increased cancer risk.

The researchers found chlordane exposure was associated with lower IL-1ß cytokine expression, which affects tumor suppression. Lower IL-1ß levels diminish the body’s natural tumor-fighting ability.

They also found a link between permethrin exposure and lower anti-inflammatory cytokine IL-10 levels.

“IL-10 is an anti-inflammatory and immunoregulatory cytokine produced by a variety of immune cells including T cells, B cells, monocytes and mast cells,” the Neta scientists wrote. “Diminished IL-10 expression has been found to be associated with asthma and allergic rhinitis.”

The 2008 study Interleukin-10: New Perspectives on an Old Cytokine (Mosser) called IL-10 the “founding member of a family of cytokines” including IL-19, IL-20, IL-22 and several others. These cytokines regulate the body’s immune response but also skin development, blood creation, epidermal cell function and mucosal, cutaneous and antiviral immunity.

A 1999 study, Prenatal Immunotoxicant Exposure and Postnatal Autoimmune Disease (Holliday), states prenatal exposure to chlordane has a more persistent and dramatic effect than adult exposure. The Holliday study showed prenatal chlordane exposure caused lifelong immunosuppression in mice.

“Selective and persistent immune alterations have been observed in mice following gestational exposure to the organochlorine insecticide chlordane, including a significant depression of cell-mediated immunity still present 101 days after birth,” the Holliday study states. “Mice exposed to chlordane during fetal life also display reduced numbers of granulocyte-macrophase colony-forming units and colony-forming units in the spleen at 200 days of age as well as long-term depression of both delayed-type hypersensitivity and mixed lymphocyte reactivity.”

The Holliday researchers noted similar immune effects were not seen in adult mice exposed to chlordane.

Numerous studies link chlordane exposure to increased non-Hodgkin lymphoma (NHL) risk. A 2008 study entitled Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma (Colt) examined carpet dust extracted from the homes of National Cancer Institute – Surveillance, Epidemiology and End Results (NCI-SEER) case study participants for organochlorine-based pesticides, including chlordane. The Colt scientists found the participants were more likely to develop NHL if their carpets contained elevated chlordane levels, or if their homes were treated with chlordane before its 1988 ban in the United States.

“There is a substantial amount of data, predominantly experimental, showing that these compounds can influence immune function,” the Colt researchers state. “Both cis-nonachlor and trans-nonachlor led to an increased susceptibility for mice to bacterial infection, suggesting that the chemicals are immunosuppressing. In humans, exposure to chlordane was associated with decreased lymphocyte responsiveness and the frequent presence of autoantibodies.”

The Colt scientists said their findings suggest organochlorines, including chlordane, affect NHL risk through biological mechanisms involving the immune system.

“Interaction between organochlorine exposure and immune gene variation is plausible, given the observed effects of organochlorines on the immune system, the known relation between immune alteration and NHL risk, and the observed associations between common variants in immune and inflammatory response genes and NHL risk,” the Colt authors state.

Another study published a year earlier, Organochlorines And Risk of Non-Hodgkin Lymphoma (Spinelli), examined six pesticide-related chemicals and their NHL connection. Oxychlordane, a chemical created when the body breaks down chlordane, showed a strong association.

Subjects with elevated levels of oxychlordane in their bloodstream were up to 69% more likely to have NHL. “Oxychlordane remained statistically significant after adjustment for all other organochlorine compounds,” the Spinelli study states.

Chlordane’s dangers aren’t limited to homeowners. The 2007 study Occupational Exposure to Organochlorine Insecticides and Cancer Incidence in the Agricultural Health Study (Purdue) examined the link between pesticides and their health effects on their applicators.

The Purdue scientists used data from the Agricultural Health Study, a prospective study of 57,311 Iowans and North Carolinians licensed to apply restricted-use pesticides. Researchers surveyed participants on their use of certain pesticides, and then tracked cancer incidence within the group over time to find potential connections.

The scientists found a statistically significant risk of rectal cancer among participants who reported chlordane use, as well as higher than normal leukemia risk for those who use both chlordane and related chemical heptachlor.

“Chlordane and heptachlor are established carcinogens in animal models, with orally administered doses clearly demonstrated to induce liver tumors in mice and rats,” the Purdue study states.




Chlordane was sold in the United States from 1948 to 1988 as an insecticide. It was used in approximately 30 million households to protect homes from termites, as well as on crops including corn and citrus, and on lawns and domestic gardens.

Following the World War II building boom, home builders pumped thousands of gallons of chlordane into the ground to protect homes against termites. When the Formosan termite, an aggressive new breed, appeared Stateside the 1960s, exterminators sought permits to use even stronger chlordane concentrations to keep the bugs out of homes. This use eventually fell out of favor when it was discovered chlordane didn’t wipe out termite colonies. The chemical merely acted as a barrier, allowing termite colonies to flourish outside homes and eventually pierce the barrier through sheer numbers. Termites kept out of homes through chlordane use would also damage living trees outside the barriers.

The U.S. Environmental Protection Agency (EPA) banned all chlordane usage in 1983 except for termite control. It was banned entirely by 1988. Chlordane breaks down very slowly and sticks strongly to soil particles, remaining in the environment for many years. Air tests in government housing found 10 to 15 times the minimal chlordane risk levels, 32 years after the last chlordane treatment.

Velsicol Chemical Corporation, headquartered in Rosemont, Illinois, was the only U.S. chlordane manufacturer. The company ceased selling chlordane for consumer use in 1987, but continues to export the chemical overseas. A Mother Jones report said, the company “phased out” chlordane manufacturing, citing market pressures. Chlordane’s trade names include Chlor-Kil, Chlortox, Corodane, Gold Crest, Kilex, Kypchlor, Niran, Octachlor, Synchlor, Termi-Ded, Topiclor, Chlordan, Prentox and Penticklor. The chemical was part of many pesticide products sold in home improvement stores and also used by exterminators.

Private equity firm Arsenal Capital Partners acquired Velsicol in 2005. The company also manufacturers flame retardants, food additives and plasticizers.

Chlordane is highly fat soluble, meaning humans can ingest it via eating high-fat foods from animals contaminated with the pesticide and then unknowingly store the chemical in their fat cells. It is excreted slowly from the body and bio-accumulates in body fat with age.

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