Issue 31 – DEHP, Inflammation

The role of DEHP in inflammation and compromised immune responses in neonates

Neonatal Intensive Care Unit

Premature infants can be exposed to high levels of pthalates. There is concern about the reproductive toxicity of DEHP, but also about its effect on the immune system. (Image: Bob J Galindo, Wikimedia)

Classified as a CMR (carcinogenic, mutagenic or reprotoxic), DEHP has been banned in Europe from use in children’s toys. In 2003, the American Academy of Pediatrics expressed concern about the potential reproductive and developmental toxicity of DEHP (Shea 2003). In 2009, DEHP became one of the first chemicals to be listed under the European Union’s REACH chemicals legislation as a Substance of Very High Concern (SVHC).

DEHP is, however, still widely-used in medical devices. Premature infants undergoing intensive care are probably the group most highly-exposed to DEHP. Depending on the intensity of medical care, researchers have found evidence of exposure up to 100 times higher than what is considered to be a safe daily level (Koch et al. 2006).

In addition to concerns about its reproductive toxicity (Martino-Andrade & Chahoud 2010) and effects on the thyroid system (Ghisari & Bonefeld-Jorgensen 2009), a growing body of research suggests that DEHP also creates problems around neonatal immune responses, potentially leading to a range of immediate health complications, particularly in neonates undergoing intensive medical treatment.

Inflammation increases blood-flow to sites of infection or injury. This allows more components of the immune response such as white blood cells to move to the site of infection and ensures the infection stays local, preventing entry to the blood and spreading to other tissue compartments.

Neutrophils are the most common type of white blood cell. Once at the target site they ingest pathogens and then die; the main component of pus, they give it its off-white colour. It is vital for proper immune response that neutrophils die immediately upon ingesting pathogens otherwise inflammatory responses can be made worse rather than better.

DEHP is known to encourage inflammation in both rats and humans (Gourlay et al. 2003). Researchers have also found that MEHP, the main metabolite of DEHP in the body, suppresses signals which encourage proper anti-inflammatory responses in the body, increasing neutrophil activity and slowing the rate at which they die (Vetrano et al. 2010).

Increased neutrophil activity and delayed neutrophil death both exacerbate inflammatory responses. Inappropriate inflammation can result in allergic reactions, anaphylaxis, autoimmune problems and recurrent or chronic infections. In addition, neutrophils contain substances for killing pathogens which, if released on healthy tissue, will cause oxidative damage to healthy cells and make inflammation worse.

Inflammation is a major risk factor in a range of neonatal health problems including bronchopulmonary dysplasia (BPD), a chronic lung disorder most common among premature children undergoing prolonged mechanical ventilation, and necrotising enterocolitis (NEC), a condition where portions of the gut undergo tissue death.

Research has implicated DEHP in both BPD (Roth et al. 1988) and NEC, where infants who have succumbed to NEC have been found to have significantly higher levels of DEHP in gastrointestinal tissue than those without the disease (Hillman et al. 1975).

Phthalates are still widely-used in medical devices, though alternatives are increasingly available for almost all uses except blood bags. Premature infants undergoing total parenteral nutrition (TPN) have been found to be less likely  to suffer from cholestasis, a condition in which the bile duct becomes blocked and for which inflammation is a risk factor, after substitution of DEHP-containing equipment for a PVC-free alternative (von Rettberg et al. 2009).

The presence of DEHP metabolites has also been associated with preterm birth (Adibi et al. 2009 and Meeker et al. 2009). This has been linked to the inflammatory effect of DEHP on the placenta (Latini et al. 2003). Birth weight is a very significant determinant of infant health.

5&5: Key news and science from September

News

Biosolids Tracking Efforts a Jumble of Research With No Clear Answers: The NYT with a very detailed article on the challenges faced by a nascent research programme into the possibility that using sewage sludge on fields might be harming health.

In Feast of Data on BPA Plastic, No Final Answer: The NYT reports on the BPA debate, saying “where science has left a void, politics and marketing have rushed in… with one side dismissing the whole idea of endocrine disruptors as junk science and the other regarding BPA as part of a chemical stew that threatens public health.”

New York to Require Disclosure of Chemicals in Cleansers: For the first time, the State of New York will begin requiring household cleaning companies to reveal the chemical ingredients in their products and any health risks they pose.

Weight Loss May Release Stored Toxins: Environmental pollutants trapped in fat cells could be released back into circulation when people shed a lot of weight, researchers have said. Compared with participants who reported large weight gains over the previous decade, those claiming large losses had 50% higher serum levels of six pollutants.

Child’s cancer risks rise ‘before pregnancy’: WHO expert recommends “parents seek to reduce their baby’s risk of cancer as an adult by steps such as eating less tinned food, reducing exposure to chemicals, limiting their child’s television viewing to encourage active play habits.”

Science

Bisphenol A Exposure during Pregnancy Disrupts Glucose Homeostasis in Mothers and Adult Male Offspring: Study finding that BPA exposure aggravates the insulin resistance that occurs during pregnancy. 4 months postpartum, BPA-treated mice weighed more and had more severe insulin resistance, changed altered levels of sugar homeostasis hormones, and molecular changes indicating reduced insulin sensitivity in skeletal muscle and liver.

Low Dose of Some POPs Predicts Type 2 Diabetes: Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity.

Neonatal Exposure to Bisphenol A and Reproductive and Endocrine Alterations Resembling Polycystic Ovarian Syndrome in Adult Rats: Study in rats finding a potential link between neonatal exposure to high doses of BPA and development of polycystic ovarian syndrome.

Higher PFOA and PFOS levels associated with higher cholesterol levels: Study consistently observing associations between increasing PFOA and PFOS and elevated total cholesterol and LDL-C levels, with authors stating this warrants further study.

Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure: New study (AOP) finding firstly, that animal models of BPA metabolism are applicable to humans, and secondly that human exposure is likely much higher than thought.

See our on-line archive of news and science for the latest studies and media reporting around how environmental chemicals affect health.

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  1. […] Issue 31 – DEHP and Inflammation […]


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