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UCSF Team Uses Mass Spec to Test Pregnant Women for Chemical Exposures

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(NEW YORK) 360Dx – Using high-resolution mass spectrometry, researchers at the University of California, San Francisco, have detected a variety of environmental chemicals in blood from pregnant women.

In a study published this week in Environmental Health Perspectives, the scientists detected an average of 56 possible environmental organic acids (EOAs) present in each subject and confirmed the presence of six of them.

The work is the first to use mass spec to screen for EOAs in pregnant women and is part of a larger effort to develop the technology for use in monitoring people for exposure to environmental chemicals, said Tracey Woodruff, professor of obstetrics, gynecology, and reproductive sciences at UCSF and senior author on the paper.

Mass spec is commonly used for testing environmental samples like drinking and waste water or soil for exposure to potentially harmful chemicals or contaminants, but Woodruff said the technology has not been as widely used for screening biological samples.

She added that while organizations like the US Centers for Disease Control and Prevention do regularly test biological samples for chemical exposure, this work is typically done using targeted methods looking for several hundred predetermined analytes. However, she said, there are tens of thousands of chemicals currently registered for use in the US, with around 8,000 produced or imported in quantities greater than 25,000 pounds per year.

"We have this large potential chemical universe that people are exposed to, but we don't have a good method to scan for what those exposures are, and we're kind of stuck right now," Woodruff said. "CDC has the capacity to measure about 350 [chemicals], but it's not all in the same run. They do a sample, and then they do a different sample. With this, we put one blood sample in, and we can run it all at once. [The process] could be more efficient, and it could be a broader scan of chemicals."

To address the wide range of potential chemical exposures and the lack of targeted mass spec assays to the vast majority of them, Woodruff and her colleagues aimed to develop an untargeted mass spec screening approach. Using an Agilent QTOF 6550 instrument, they screened serum collected from 75 pregnant women and identified 696 potential EOAs based on successful matches (based on accurate mass) to candidates in the researchers' EOA database, which they compiled using data from public sources including the Environmental Protection Agency, the California Department of Pesticide Regulation, and literature searches.

They then set out to prioritize potential EOAs for further confirmation based on several criteria designed to identify EOAs that have not been previously monitored in people.

First, they ranked the suspect compounds based on the frequency of their detection and prioritized those that differed in detection frequency or the quantity of their presence across different demographic groups.

Next, they excluded candidates that were phthalate metabolites, as most of those have been monitored by either the California Biomonitoring program or the CDC's National Health and Nutrition Examination Survey. They also excluded candidates predicted to be pesticide metabolites due to the difficulty of matching those compounds to their EOA database and the fact that commercial standards were not available for these metabolites.

Then they searched various biomonitoring and chemical databases to eliminate from consideration candidate compounds that were currently being biomonitored, were not used in consumer products, or were not considered potential human carcinogens.

Having winnowed down their list in this manner, Woodruff and her colleagues sought out chemical reference standards for the remaining candidates, purchasing those that were available, which amounted to 20 total candidates. Comparing the retention time, accurate mass, and MS/MS spectra for the reference standards to those of the endogenous molecules, they identified with high confidence six EOAs — 2,4-di-tert-butylphenol, pyrocatechol, 2,4-dinitrophenol, 3,5-di-tert-butylsalicylic acid, 4-hydroxycoumarin, and 20-hydroxyacetophenone — as present in maternal serum, the first two of which, the authors noted, "are high-production-volume chemicals in the United States."

While the confirmed EOAs represent just a fraction of the potential chemicals people could be exposed to, the study provides proof of principle that an untargeted, high-res mass spec method can identify compounds in human samples not previously screened for. Woodruff suggested this was notable given the limitations biomonitoring studies have traditionally faced.

"A lot of epidemiological studies wanted to use biomonitoring to look at the relationships between human exposures and [health outcomes]," she said. But, in many cases, such studies were limited by measurement capabilities.

"We could [develop a study] based on what the chemical we thought was most important in terms of what we're most interested in, pregnancy outcomes," she said. "We had to do it based on what labs we could find could measure what chemical. And that's really not a good way to do science."

Key to further developing the method will be building out the search database the researchers used to identify their suspected compounds. Currently, that database contains mass spec data on around 3,000 chemicals, but ultimately the UCSF team hopes to push its contents to around 8,000 chemicals, Woodruff said.

While her team's biomonitoring work is still focused largely on technology development at this point, Woodruff said her long-term goal is to better understand the effect of different chemical exposures and the interactions of those exposures on human health.

"There's a lot of exciting work [to be done] in terms of comparing different populations with different types of health effects and the [different] chemical exposure between diseased [and] not diseased," she said. "And then, ultimately, we want to identify those that are harmful and stop those exposures."

In the near-term, Woodruff said she and her colleagues are testing the approach in a larger cohort of around 200 patients and also looking at cord blood to investigate fetal exposure to different chemicals. They also plan to compare the chemical profiles of women with children with lower and higher birth weights to determine if there are any differences in their levels of exposure.