Growing up with pesticides

SALINAS VALLEY, CALIFORNIA—It's a sunny July day, sweltering by midmorning. Fields with meticulously maintained rows of lettuce and bushy, berry-laden strawberry plants stretch to the horizon. Farm workers wearing brightly shaded headscarves and layers of clothing—most of them low-income Mexican immigrants—dot the fields. This is "America's salad bowl," a region that grows much of the produce found in grocery stores throughout the country.

At about 3 p.m. in the afternoon, Guillermina Aguilar walks into a small office with her husband and their 12-year-old son Eric, who's about to undergo a series of tests. Aguilar and her family are part of a long-term study into the effects of pesticides and other environmental chemicals at the Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS, which is also Mexican slang for "little kids."

Aguilar enrolled in the study when she was pregnant with Eric. At the time, the family lived two blocks from the fields, where the pungent, sweet odor of pesticides often hung heavy in the air. "Sometimes in the mornings I remember I would ask my husband, 'What's that smell?'" Aguilar recalls. But they became accustomed to it. "That was normal for us at that time," Aguilar says. Today she lives in Arkansas; Eric's 12-year assessment takes place during a family visit.

The program, run by the University of California (UC), Berkeley, is one of three U.S. studies that have followed children since the late 1990s to investigate the impact of chemicals in the environment on their brains. The Berkeley program focuses on an agricultural area in California; studies at Columbia University and Mount Sinai School of Medicine look at multiethnic, low-income inner city families in New York City.

The outcomes so far are troubling, although they have been questioned by the pesticide industry. The studies suggest that organophosphates, a widely used class of pesticides that act on the central nervous system, hamper the development of some parts of the brain in children, leading to lower IQs and attention problems. Preliminary evidence also suggests that pesticide exposure may affect sexual differences in certain brain regions during early childhood development.

A main culprit in the Columbia study, chlorpyrifos, was phased out in 2001 for most residential use, and urban exposure in the United States has dropped dramatically—but it's still widely used in agriculture. And a whole generation may already be suffering subtle but prolonged effects, says epidemiologist Virginia Rauh, deputy director of the Columbia Center for Children's Environmental Health.

Critical stages

Research in lab animals and farm workers has shown that chronic exposure to high doses of pesticides is associated with neuro-degenerative diseases such as Parkinson's disease and cognitive deficits. More recently, researchers started looking at how exposure in the womb and in infancy affects the developing brain—a quest spurred in part by a growing awareness of neurobehavioral and neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) and learning disabilities. In the 1990s, "we realized that we needed to understand what children were being exposed to in the womb and in the early months and years of their lives," says Frederica Perera, director of the Columbia center.

All three studies recruited hundreds of pregnant mothers in the late 1990s, measured their exposure to environmental chemicals, and gave their kids a battery of tests at various intervals. The Columbia researchers also obtained umbilical cord blood samples directly after birth, allowing them to measure fetal exposure to several pesticides directly; the Berkeley team collected urine samples during pregnancy and early childhood, and searched for pesticides' breakdown products. The researchers compared the intellectual development of children with varying levels of pesticide exposure within each group, controlling for confounding variables such as sex, race or ethnicity, maternal education, family income, and other toxic exposures.

Early on in the Berkeley study, infants with high fetal exposures showed abnormal reflexes. At age 2, the highly exposed children had lower mental development, and the researchers found an increase in ADHD-like behaviors at age 5. At age 7, highly exposed children scored 7 points lower on the fulls-cale IQ score, which includes tests of verbal comprehension, working memory, processing speed, and perceptual reasoning—a drop similar to that found in studies of childhood lead exposure. It translates to about a 6-month developmental lag, says reproductive epidemiologist Kim Harley of the UC Berkeley center.

While the California study looked at a range of organophosphates used in agriculture, the Columbia team zoomed in on chlorpyrifos, which was widely used indoors to kill ants, termites, and cockroaches. Even after indoor use largely ended in 2001, it's still used to control agricultural pests under the Dow Chemical trade name Lorsban. The company also continues marketing chlorpyrifos for residential use in developing countries.

The Columbia team realized that chlorpyrifos might be important after they discovered detectable levels in the umbilical cord blood samples from 71% of their pregnant women in the late 1990s. "That was a wake-up call for all of us," says Columbia University molecular epidemiologist Robin Whyatt. "Whereas one generally thought about pesticides as an agricultural risk, it really became clear that in New York City, because of the cockroach problem, they are definitely an urban risk as well."

The team found that infants with high exposures to chlorpyrifos and another commonly used organophosphate called diazinon had lower birth weight and birth length, "on the order of what one would see with active cigarette smoking during pregnancy," Whyatt says. The team also reported abnormal reflexes in newborns, as well as deficits in IQ and attention, and behavioral problems as the children matured.

Rauh, along with Columbia developmental neuropsychiatrist Bradley Peterson, also performed an MRI study on the brains of 40 children aged 5 to 11, half of them from the high exposure group. In a 2012 paper in the Proceedings of the National Academy of Sciences, they reported that the volumes of a number of brain regions that are important in emotion, social cognition, and inhibition were altered in highly exposed children. What's more, some normal sex-specific differences in the sizes of certain brain regions were not seen in children with high prenatal exposure—findings consistent with effects seen in animals. That suggests chlorpyrifos may interfere with normal sexual differentiation of the brain, Rauh says—although what that means for the kids is unclear. The team is now conducting a study in 250 children to confirm the results.

Chlorpyrifos and other organophosphates work by inhibiting cholinesterase, a family of enzymes that break down acetylcholine, a neurotransmitter that plays many key roles in the brain. When exposure occurs during prenatal development, these compounds "essentially misdirect the assembly of the brain," says Theodore Slotkin of Duke University in Durham, North Carolina, who has extensively studied pesticides' effects on animals.

State of the art

Dow Chemical has long tried to poke holes in the research that finds detrimental effects from pesticides. In response to the imaging study, for instance, the company issued a statement pointing to what it says are limitations in the research, such as the fact that the scans "provide only a single snap-shot in time," and that confounding factors were controlled "only imperfectly or not at all." A company spokesman adds that "no mechanism of action has been determined by these researchers that would explain how these outcomes would come about."

Joseph Braun, an epidemiologist at Brown University, calls the imaging study "cutting edge and very novel" but cautions that replication is necessary. Bruce Lanphear, a pediatric epidemiologist at Simon Fraser University, Vancouver, in Canada, says that the MRI results weren't surprising. In 2008, he and others reported similar structural brain changes associated with childhood lead exposure. Lanphear calls the cohort studies "highly regarded" and "state of the art." "Pesticides were designed to be neurotoxic," he says. "Why should we be surprised if they cause neurotoxicity?" (Neither Braun nor Lanphear was involved in the study.)

The indoor regulation on chlorpyrifos has reduced exposure in some populations, and use of that compound and other organophosphates is steadily declining in U.S. agriculture as well. But researchers worry about the safety of their replacements, such as the pyrethroids, which now comprise the majority of household pesticides and are also heavily used on farms. Harley likens the succession of chemicals to a game of "whack-a-mole," in which one compound is banned, only to be replaced by another whose safety is not assured.

As noon approaches under the relentless California sun, workers—men and women—are bent over, quickly and methodically shaking the strawberry plants, plucking the reddest and ripest of the berries, then stacking them inside clear, plastic cartons labeled with common household names. It would be difficult to grow all of this produce at the current prices without pesticides; the CHAMACOS researchers are the first to admit that it's a complex problem. "Now that we've been in the Salinas Valley for 13 years, we get to see all sides of the issue," says Berkeley epidemiologist Brenda Eskenazi, who heads the study.

Harley agrees—but given the choice, she buys mostly organic produce. Not just to protect her own children, she says, but those of the men and women working in these fields.

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Amanda Mascarelli is a science writer based in Denver, Colorado. Her reporting was supported by the California Endowment Health Journalism Fellowships, a program of the University of Southern California's Annenberg School of Journalism http://www.reportingonhealth.org/.

Image by Andy Powell via Flickr