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New study shows prenatal chemical exposure can slow development in boys

Boys exposed to a group of common chemicals while still in the womb may experience slowed development in childhood, according to a new study by researchers at UC Berkeley School of Public Health.

The chemicals, called phthalates, are widely used in personal care products such as shampoo, hair spray, and soap, as well as plastic packaging and other consumer goods. They have long been known to disrupt the endocrine system, which can set the stage for a wide range of developmental and health problems.

This study, recently published online ahead of print in Environmental Research, is the first evidence that prenatal exposure to DEHP, a common phthalate, is also associated with decreased epigenetic age acceleration at age seven; meaning that the boys’ development lagged behind their chronological age.

“This is one of the very few studies in general of epigenetic acceleration in children, and the very first cohort in the world looking at prenatal phthalate exposure,” said Nina Holland, a co-author and research professor emeritus of environmental health. “It’s a hot new research area.”

In addition, Holland said, no previous research has examined changes in epigenetic acceleration in children at multiple points in time, as the investigators have in this study, examining children at birth, and at ages 7, 9, and 14.  No significant impacts were observed aside from 7-year-old males. They are now analyzing data to determine whether there is any effect on males or females at age 18.

“We’ve demonstrated that it’s really important to look at the different stages of growth and development, because findings of exposure, prenatal exposure may only become evident several years after the child is born,” she said. “This is very critical in understanding what it all means for epigenetic acceleration.”

The work is an expansion of the epigenetic studies in children conducted in Holland’s Laboratory of Children’s Environmental Health over the past 15 years.

Earlier studies by researchers at Berkeley Public Health and elsewhere have found that environmental exposures to tobacco smoke, organochlorine pesticides, ambient air pollution, and certain industrial chemicals were associated with greater epigenetic age acceleration. But there was a lack of literature on prenatal exposure to phthalates and epigenetic age acceleration during childhood.

The first author of the paper, doctoral candidate Dennis Khodasevich, said he sought to fill the knowledge gap by utilizing 15 years of longitudinal data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort. CHAMACOS,  launched in 1999 and led since then by Brenda Eskenazi, director of the UC Berkeley School of Public Health’s Center for Environmental Research and Community Health,  is a unique study that contains 20 years of data and nearly 300,000 biological samples for analysis of children’s development and environmental exposures in a Latino farmworker community.

In 2022, graduate student Saher Daredia led an investigation, published in Epigenetics,  that found similar epigenetic age acceleration at birth in relation to several maternal factors, including serum lipid levels, preterm birth, and the number of live births prior to the current pregnancy.

For the new study, Investigators drew on the CHAMACOS “library” to test associations between prenatal urinary concentrations of 11 common phthalate metabolites and epigenetic age acceleration in early life.

“The epigenetic clock starts ticking at birth and continues throughout the life course,” said Khodasevich. “The clocks are very responsive to genetic factors and also to cumulative environmental exposures, as well as various social factors.

“We’re still trying to understand what it means if they slow down or speed up in children—most of the focus has been on adults,” he said.

The prenatal exposures to phthalate occurred around 1999 to 2000. Since then, some phthalates have been phased out due to their carcinogenicity and endocrine-disrupting effects. The Consumer Product Safety Improvement Act of 2008 permanently prohibited children’s toys or child care articles containing concentrations of more than 0.1 percent of three types of phthalates. In 2022, the Food and Drug Administration revoked authorization for several phthalates for use in materials that are in contact with food. Some states and the European Union have also banned certain phthalates.

But phthalate use continues to be widespread. One of the biggest sources of exposure to phthalates and other endocrine-disrupting chemicals is in personal care products and cosmetics.

“We’re especially concerned with the higher concentrations of these toxic compounds in products targeted towards women of color,” Khodasevich said. “These products often contain the most endocrine-disrupting chemicals, and it contributes to existing health disparities.”

The study will appear in the August 15, 2023, issue of Environmental Research.

Additional authors include: Alan Hubbard, Kim Harley, Julianna Deardorff and Brenda Eskenazi from UC Berkeley School of Public Health; and corresponding author Andres Cardenas, formerly at BPH, now at Stanford University School of Medicine.

Funding was provided by the National Institute of Environmental Health Sciences (NIESH), the National Institute on Aging, and the National Institute on Minority Health and Health Disparities.