4-n-Nonylphenol and bisphenol A are endocrine disrupting chemicals that are mainly detoxified through glucuronidation. A factor that may modulate their glucuronidation rates is co-exposure to pharmaceuticals.

This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors. Nonylphenol and bisphenol A were co-incubated in freshly isolated rat hepatocytes with, drugs at a high concentration.

Statistically significant metabolic inhibition of bisphenol A and nonylphenol biotransformation was observed with nine drugs (>50% inhibition by naproxen, salicylic acid, carbamazepine and mefenamic acid). Inhibition assays of UGT activity in rat liver microsomes revealed: 1) competitive inhibition by naproxen (K(i)(app) = 848.3 muM) and carbamazepine (K(i)(app) = 1023.1 muM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition.

Detoxification of nonylphenol and bisphenol A was shown to be impaired by excessive concentrations of many drugs and health risk assessment should therefore address this issue.

Reference: Verner MA, Magher T, Haddad S., High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol A and nonylphenol in rats, Xenobiotica. 2009 Nov 16.

A study of 145 preschool children reports, for the first time, that when the concentrations of two common phthalates in mothers’ prenatal urine are elevated their sons are less likely to play with male-typical toys and games, such as trucks and play fighting.

The University of Rochester Medical Center-led study is published in the International Journal of Andrology.

Because testosterone produces the masculine brain, researchers are concerned that fetal exposure to anti-androgens such as phthalates “which are pervasive in the environment“ has the potential to alter masculine brain development, said lead author Shanna H. Swan, Ph.D., professor of Obstetrics and Gynecology, director of the URMC Center for Reproductive Epidemiology, and an expert in phthalates.

“Our results need to be confirmed, but are intriguing on several fronts,” Swan said. “Not only are they consistent with our prior findings that link phthalates to altered male genital development, but they also are compatible with current knowledge about how hormones mold sex differences in the brain, and thus behavior. We have more work to do, but the implications are potentially profound.”

Phthalates are chemicals used to soften plastics. Recent studies have shown that the major source of human exposure to the two phthalates of most concern (DEHP and DBP) is through food. These phthalates are used primarily in polyvinyl chloride (PVC), so any steps in the processing, packaging, storage, or heating of food that use PVC-containing products can introduce them into the food chain.

Phthalates are also found in vinyl and plastic tubing, household products, and many personal care products such as soaps and lotions. Phthalates are becoming more controversial as scientific research increasingly associates them with genital defects, metabolic abnormalities, and reduced testosterone in babies and adults. A federal law passed in 2008 banned six phthalates from use in toys such as teethers, play bath items, soft books, dolls and plastic figures.

In Swan’s study, higher concentrations of metabolites of two phthalates, di(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP), were associated with less male-typical behavior in boys on a standard play questionnaire. No other phthalate metabolites measured in-utero was linked to the less-masculine behavior. Girls’ play behavior was not associated with phthalate levels in their mothers, the study concluded.

Swan’s interest in phthalates stems from an investigation into the environmental causes of reproductive health problems. Since 1998 she has led the federally funded, multi-center Study for Future Families (SFF), which established a large database from which to explore various scientific questions about toxins.

The current study focused on a small sample of SFF mothers who delivered children between 2000 and 2003. The mothers provided urine samples around the 28th week of pregnancy. The urine was analyzed for phthalate metabolites by the Centers for Disease Control and Prevention (CDC).

Swan hypothesized that phthalates may lower fetal testosterone production during a critical window of development – somewhere within eight to 24 weeks gestation, when the testes begin to function – thereby altering brain sexual differentiation.

To explore the question, researchers reconnected with mothers from the SFF sample and asked them to complete a standard research questionnaire, called the Preschool Activities Inventory (PSAI), for their children ages 3 1/2 to 6 1/2 years.

The PSAI is designed to discriminate play behavior within and between the sexes, and in the past has been shown to reflect the endocrine-disrupting properties of other toxins, such as PCBs and dioxins. The PSAI addressed three aspects of play: types of toys children choose (trucks versus dolls), activities (rough-and-tumble play, for example), and child characteristics.

However, researchers were concerned about how the choice of toys available in any given household might skew results, so in addition they asked about parental views toward atypical play. For example, the survey asked, “What would you do if you had a boy who preferred toys that girls usually play with?” The possible answers included “strongly encourage” (him to play this way) to “strongly discourage.”

The final survey scores are designed to reflect sex-typical play. Higher scores meant more male-typical play and lower scores meant more female-typical play.

Researchers then examined boys play-behavior scores in relation to the concentration of phthalate metabolites in their mothers’ prenatal urine samples, finding that higher concentrations of DEHP and DBP metabolites were associated with less masculine play behavior scores.

Earlier studies by Swan and others have shown that phthalate exposure during pregnancy might affect the development of genitals of both male rodents and baby boys. Scientists refer to this cluster of genital alterations as the “phthalate syndrome,” and research suggests that in rodent pups, the syndrome can have adverse consequences for later sexual development.

If endocrine disrupters such as phthalates can impair genital development and hormone levels in the body, the play-behavior study noted, then a deeper examination of how these chemicals impact the brain is warranted.

Reference: University of Rochester Medical Center, Pilot study relates phthalate exposure to less-masculine play by boys, Nov. 16, 2009

If it hadn’t been for the Big Macs that Joannie ate pretty much three times a week, she wouldn’t have gotten fat.  If she hadn’t been exposed while in her mother’s womb to chemicals x, y and z, Joannie wouldn’t have had the propensity to get fat.  And if Joannie’s mom had eaten more sensibly, both waistlines would be slimmer.

Fat people most likely are programmed to become fat before taking their first sip of milk.

Today’s news is, that pesticides are among the chemicals responsible for this reprogramming.

Two of three U.S. adults are now classified as overweight.  Type II diabetes has increased in like measure over the same decades, and so has heart disease.  This is not a coincidence.  These illnesses share common characteristics: they are triggered while in the womb by exposure to the same kinds of chemicals and the outcomes show up in adulthood.  Scientists now call this pattern “the fetal origins of adult diseases”.

The most likely culprits are chemicals now grouped together under the rubric “endocrine disrupters.” It’s been known for about two decades, though disputed by the manufacturers, that these chemicals alter the normal signaling pathways of hormones.  Think of Bisphenol A (BPA), right now the nation’s most celebrated endocrine disruptor.

Pesticides, though not specifically thought of as endocrine disruptors nor regulated as such, can similarly knock normal development off track.  Research has just found that a family of pesticides among the most widely used in the world is connected to these three adult illnesses.  This is the family of organophosphates, concocted from petroleum with an addition of phosphoric acid.

When lab rats are exposed to these pesticides through the mother’s diet, at a time in their development equivalent to a human baby’s second trimester in the womb, their metabolism changes in two ways: their cholesterol and triglycerides rise.  These abnormal and lasting changes resemble the major factors that predict and lead, later in life, to obesity, diabetes and cardiovascular heart disease (specifically, atherosclerosis, a condition in which fatty material collects along the arteries and hardens artery walls).

These changes in metabolism happen at low levels, within the levels we are uniformly exposed to, which the Environmental Protection Agency declares as “safe” but are evidently not.  The changes are the strongest when the mother rats are fed a high-fat diet.  Human babies may even be underweight at birth (and there’s an epidemic of underweight babies in the U.S.), but quickly become overweight

Humans run into these pesticides in our food and water.  Of course, children continue to be exposed once they are born and are in fact exposed more than adults because they eat and drink more in relation to their body weight and have a higher ratio of skin.

The other groups of people exposed most to organophosphates and other pesticides are the same groups with the highest rates of obesity – people who live in run-down inner-city neighborhoods, the poor, and farmworkers.  Again, not a coincidence but a connection, a trigger.

Dr. Ted Slotkin of Duke University, the researcher responsible for these discoveries, found another compelling clue: exposure caused harm to the rodent’s brain, as well as its metabolism.  Once the exposed lab animal was born and started to eat at will, its consumption of a high-fat diet reduced the adverse symptoms in its brain functioning.  As Dr. Slotkin muses, “If you’ve got neurofunctional deficits, and they can be offset by continually eating Big Macs, then you will naturally (but unconsciously) select that kind of food because it will make you feel better.”  Unfortunately, increased fat will further harm the animal’s, or human’s, metabolism.

What this means for you:

Particularly while trying to conceive, during pregnancy, while nursing, and for your children, avoid pesticides; eat organic foods.

For information about endocrine disruptors, read the new booklet published by the nonprofit Learning and Developmental Disabilities Initiative.

Author: Alice Shabecoff for CSN – Chemical Sensitivity Network, November 5, 2009

Alice Shabecoff is the co-author with her husband Philip of Poisoned Profits: The Toxic Assault on our Children, published by Random House last year.  See their website, www.poisonedprofits.com

Related article from Alice Shabecoff:

• Our planet, our children – How are your children doing?

Plumes of harmful air pollutants can be transported across oceans and continents — from Asia to the United States and from the United States to Europe — and have a negative impact on air quality far from their original sources, says a new report by the National Research Council.  Although degraded air quality is nearly always dominated by local emissions, the influence of non-domestic pollution sources may grow as emissions from developing countries increase and become relatively more important as a result of tightening environmental protection standards in industrialized countries.  

“Air pollution does not recognize national borders; the atmosphere connects distant regions of our planet,” said Charles Kolb, chair of the committee that wrote the report and president and chief executive officer of Aerodyne Research Inc.  “Emissions within any one country can affect human and ecosystem health in countries far downwind.  While it is difficult to quantify these influences, in some cases the impacts are significant from regulatory and public health perspectives.” 

The report examines four types of air pollutants: ozone; particulate matter such as dust, sulfates, or soot; mercury; and persistent organic pollutants such as DDT.  The committee found evidence, including satellite observations, that these four types of pollutants can be transported aloft across the Northern Hemisphere, delivering significant concentrations to downwind continents.  Ultimately, most pollutants’ impacts depend on how they filter down to the surface.  

Current limitations in modeling and observational capabilities make it difficult to determine how global sources of pollution affect air quality and ecosystems in downwind locations and distinguish the domestic and foreign components of observed pollutants.  Yet, some pollutant plumes observed in the U.S. can be attributed unambiguously to sources in Asia based on meteorological and chemical analyses, the committee said.  For example, one study found that a polluted airmass detected at Mt. Bachelor Observatory in central Oregon took approximately eight days to travel from East Asia.  

The health impacts of long-range transport vary by pollutant.  For ozone and particulate matter — which cause respiratory problems and other health effects — the main concern is direct inhalation.  While the amount of ozone and particulate matter transported on international scales is generally quite small compared with domestic sources, neither of these pollutants has a known “threshold,” or concentration below which exposure poses no risk for health impacts.  Therefore, even small incremental increases in atmospheric concentrations can have negative impacts, the committee said.  For instance, modeling studies have estimated that about 500 premature cardiopulmonary deaths could be avoided annually in North America by reducing ozone precursor emissions by 20 percent in the other major industrial regions of the Northern Hemisphere. 

For mercury and persistent organic pollutants, the main health concern is that their transport and deposition leads to gradual accumulation on land and in watersheds, creating an increase in human exposure via the food chain.  For example, people may consume mercury by eating fish.  There is also concern about eventual re-release of “legacy” emissions that have been stored in soils, forests, snowpacks, and other environmental reservoirs. 

In addition, the committee said that projected climate change will lead to a warmer climate and shifts in atmospheric circulation, likely affecting the patterns of emission, transport, transformation, and deposition for all types of pollution.  However, predicting the net impacts of the potential changes is extremely difficult with present knowledge. 

In the coming decades, man-made emissions are expected to rise in East Asia, the report says.  These increases could potentially be mitigated by increasingly stringent pollution control efforts and international cooperation in developing and deploying pollution control technology. 

To enhance understanding of long-range transport of pollution and its impacts, the committee recommended a variety of research initiatives, such as advancing “fingerprinting” techniques to better identify source-specific pollutant characteristics, and examining how emissions from ships and aircraft affect atmospheric composition and complicate the detection of pollution from land-based sources.  The committee emphasized developing an integrated “pollution source-attribution” system that improves capabilities in emissions measurements and estimates; atmospheric chemical and meteorological modeling; long-term, ground-based observations; satellite remote sensing; and process-focused field studies.  

Moreover, the committee stressed that the United States, as both a source and receptor of long-range pollution, has an interest in remaining actively engaged in air pollutants that travel abroad, including support of more extensive international cooperation in research, assessment, and emissions control efforts. 

The report was sponsored by the U.S. Environmental Protection Agency, National Oceanic and Atmospheric Administration, NASA, and National Science Foundation.  The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies.  They are independent, nonprofit institutions that provide science, technology, and health policy advice under an 1863 congressional charter.  Committee members, who serve pro bono as volunteers, are chosen by the Academies for each study based on their expertise and experience and must satisfy the Academies’ conflict-of-interest standards.  The resulting consensus reports undergo external peer review before completion.  For more information, visit National Academies  A committee roster follows. 

Reference: National Academy of Sciences, Air Pollutants From Abroad a Growing Concern, Says New Report, Washington, September 29. 2009

A group of chemists from the University of Santiago de Compostela (USC) has developed a method to quantify the fragrance allergens found in baby bathwater. The researchers have analysed real samples and detected up to 15 allergen compounds in cosmetics and personal hygiene products. 

A team of scientists from the Department of Analytical Chemistry, Nutrition and Bromatology at the USC has developed a method to detect and quantify the 15 most common fragrance allergens included in soap, gel, cologne and other personal hygiene products.   

“Applying the method to eight real samples obtained from the daily baths of a series of babies aged between six months and two years old, we discovered the presence of all the compounds under study in at least one of the samples,” co-author of the study published this month in Analytical and Bioanalytical Chemistry, María Llompart, explained to SINC. 

The scientists found at least six of the 15 compounds in all the samples. In some cases, concentrations were “extremely high”, exceeding 100ppm (parts per million = nanograms/millilitre). Some of the substances that appeared were benzyl salicylate, linalol, coumarin and hydroxycitronellal. 

“The presence and levels of these chemical agents in bathwater should be cause for concern,” Llompart said, “bearing in mind that babies spend up to 15 minutes or more a day playing in the bath and that they can absorb these and other chemicals not only through their skin, but also by inhalation and often ingestion, intentional or not.”

New Method to Detect Fragrances

Allergens were able to be detected due to the high level of sensitivity of the method, which for the first time applies the Solid-Phase Micro Extraction (SPME) technique to determining the ingredients of cosmetics and child hygiene products. This technique makes it possible to concentrate and isolate chemical components from a sample by absorbing them into fibres with a certain coating. 

The researchers have also employed gas chromatography to separate compounds and mass spectrometry to identify and measure the abundance of each of the fragrances. 

European regulations stipulate that the presence of such substances should be indicated on the label of the product when levels exceed a certain limit (0.1 or 0.01%, depending on the type of compound), but some associations believe these limits are excessively tolerant, particularly where child hygiene and baby and child care products are concerned. 

References: J. Pablo Lamas, Lucia Sánchez-Prado, Carmen Garcia-Jares y María Llompart. “Solid-phase microextraction gas chromatography-mass spectrometry determination of fragrance allergens in baby bathwater”. Analytical and Bioanalytical Chemistry 394 (5): 1399-1411, julio de 2009.