NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate

Di(2-ethylhexyl)phthalate (DEHP)

“…39 While DEHP does not currently warrant labeling as a human carcinogenic agent 40,41 the evidence against DEHP constitutes a realistic public health threat for highrisk populations. Citing the summary findings of the NTP report 3 -"Based on the morphological, functional and biochemical endpoints, the Sertoli cell is a cellular target for neonatal, pubertal, and adult [DEHP] exposures. Testicular toxicity in the postnatal phase of life resulting from DEHP exposure occurs because of the metabolism, to MEHP, the proximate toxicant."…”

“…43 "When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some causeand-effect relationships are not fully established satisfactorily." 44 This "precautionary" principle was cited in the NTP report 3 and was recently reviewed in detail by multiple environmental scientists. 45 Synonyms include the "foresight principle," primary prevention, "first do no harm," and prudent avoidance.…”

“…7 Neonates undergoing routine blood transfusions may be exposed to amounts of DEHP (and MEHP) that are 1-2 orders of magnitude above those noted in the general population who are exposed to the same agent. 3 Concentrations of DEHP in necropsy tissues (i.e., heart and GI) from premature infants who received varying quantities of blood products were significantly higher when compared to infants who had not received blood transfusions. 8 Regardless of transfusion history, autopsied tissues from adults exhibited similar DEHP concentrations.…”

“…16 The U.S. Environmental Protection Agency Science Policy Council took an interim position on the subject in 1998. 17 Further review regarding DEHP and human patients was issued by the National Toxicology Program's (NTP) Center for Evaluation of Risks to Human Reproduction 3 and the FDA via the Center for Devices and Radiological Health, 10 resulting in a formal FDA advisory warning to clinicians in 2002. 18 Additional evidence also implicates DEHP in causing pulmonary and hepatic effects via ECMO, parenteral nutrition and endotracheal tube use.…”

“…1 Primary routes of exposure to DEHP are inhalation, ingestion, dermal contact and through a variety of medical procedures. 3 Medical supplies containing PVC include disposable medical examination or surgical gloves, extracorporeal mem-brane oxygenation (ECMO) circuits, umbilical catheters, nasogastric tubes, intravenous (IV) and blood storage bags, and flexible medical tubing for administering parenteral products (Table 1). 3 Despite being listed as a possible human carcinogen in the 1980's, 1 recent concerns have focused on its potential reproductive toxicity as a result of leaching from medical devices into at-risk patient populations (most notably neonates) via the IV or enteral routes.…”