Hidden Toxicity in Neonatal Intensive Care Units: Phthalate Exposure in Very Low Birth Weight Infants.

OBJECTIVE: To determine exposure to endocrine-disrupting phthalates in preterm infants in neonatal intensive care units (NICU). METHODS: Urine samples (n=151) from 36 preterm infants (<32 weeks of gestation and/or <1500 g of birth weight) were collected on the first 3 days of admission to the NICU and biweekly thereafter. Diethylhexyl phthalate contents of indwelling medical devices used in various procedures and the concentrations of phthalate metabolites in the urine samples were analyzed. The relationships between urinary excretion, exposure intensity, postnatal age and birth weight were examined. RESULTS: The mean gestational age and mean birth weight of the study infants were 28.9±1.5 weeks and 1024±262 g, respectively. Diethylhexyl phthalate was detected in umbilical catheters, endotracheal tubes, nasogastric tubes, and nasal cannula. Monoethylhydroxyhexyl phthalate (MEHHP) was the most frequently detected metabolite (81.4%); its concentration increased during the first 4 weeks and then started to decrease but never disappeared. Patients who did not need indwelling catheters (except nasogastric tubes) after 2 weeks were classified as group 1 and those who continued to have indwelling catheters as group 2. Although not of statistical significance, MEHHP levels decreased in group 1 but continued to stay high in group 2 (in the 4th week, group 1: 65.9 ng/mL and group 2: 255.3 ng/mL). Levels of MEHHP in the first urinary samples were significantly higher in infants with a birth weight <1000 g (<1000 g: 63.2±93.8 ng/mL, ≥1000 g: 10.9±22.9 ng/mL, p=0.001). CONCLUSION: Phthalate metabolites were detected even in the first urine samples of very low birth weight newborns. Phthalate levels were higher in the first weeks of intensive invasive procedures and in preterm infants with a birth weight less than 1000 g. MEHHP was the most frequently detected metabolite and could be a suitable biomarker for the detection of phthalate exposure in preterm infants.

Reproductive and developmental effects of phthalate diesters in females.

Phthalate diesters, widely used in flexible plastics and consumer products, have become prevalent contaminants in the environment. Human exposure is ubiquitous and higher phthalate metabolite concentrations documented in patients using medications with phthalate-containing slow release capsules raises concerns for potential health effects. Furthermore, animal studies suggest that phthalate exposure can modulate circulating hormone concentrations and thus may be able to adversely affect reproductive physiology and the development of estrogen sensitive target tissues. Therefore, we conducted a systematic review of the epidemiological and experimental animal literature examining the relationship between phthalate exposure and adverse female reproductive health outcomes. The epidemiological literature is sparse for most outcomes studied and plagued by small sample size, methodological weaknesses, and thus fails to support a conclusion of an adverse effect of phthalate exposure. Despite a paucity of experimental animal studies for several phthalates, we conclude that there is sufficient evidence to suggest that phthalates are reproductive toxicants. However, we note that the concentrations needed to induce adverse health effects are high compared to the concentrations measured in contemporary human biomonitoring studies. We propose that the current patchwork of studies, potential for additive effects and evidence of adverse effects of phthalate exposure in subsequent generations and at lower concentrations than in the parental generation support the need for further study.

Human exposure to bisphenol A (BPA).

The plastic monomer and plasticizer bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in many consumer products. Here, we have outlined studies that address the levels of BPA in human tissues and fluids. We have reviewed the few epidemiological studies available that explore biological markers of BPA exposure and human health outcomes. We have examined several studies of levels of BPA released from consumer products as well as the levels measured in wastewater, drinking water, air and dust. Lastly, we have reviewed acute metabolic studies and the information available about BPA metabolism in animal models. The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.

Controversy: neonatal exposure to plasticizers in the NICU.

This article presents a review of extant literature that informs our current understanding of the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure on neonates. Phthalates such as DEHP add flexibility to plastics. DEHP is a major component in the manufacturing of polyvinyl chloride devices commonly used in the healthcare setting. Premature and critically ill neonates and infants in the NICU are exposed to DEHP and may be at an increased risk for adverse health outcomes as a result. DEHP has been shown to be a developmental and endocrine disrupting toxicant and is a major component in polyvinyl chloride plastics, which are commonly found in medical equipment used in the NICU. Potential toxicities to infants in the NICU are a concern because infants' small body size and compromised physical condition necessitate a multitude of medical interventions, each increasing exposure levels. Expanding nurses' knowledge regarding DEHP research is important for implementing a precautionary approach to reduce DEHP exposure among NICU patients.

Acute toxicity of tri-ortho-cresyl phosphate in sheep and swine.

Tri-ortho-cresyl phosphate (TOCP) was given orally or by subcutaneous (SC) injection to sheep and swine. Sheep given oral doses of 100, 200, or 400 mg of TOCP/kg of body weight developed an acute intoxication characterized by diarrhea dehydration, metabolic acidosis, and death within 6 days. Daily SC injections of TOCP in sheep caused either death or delayed neurotoxicosis depending upon the dosage. Increase of aspartate aminotransferase activity approximately 24 hours before the animal died and histopathologic changes confirmed that liver injury had occurred. Swine dosed with 100 to 1,600 mg of TOCP/kg had minimal signs of acute toxicosis, but developed severe delayed neurotoxicosis in approximately 15 days. Those given a 800 mg/kg dose by the oral route or SC injection had severely decreased serum acetylcholinesterase activity. In the swine which were euthanatized at 7 days after treatment, histopathologic examinations revealed no lesions (although the nervous system was not examined, because clinical neurologic signs were normal).