American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV): 5.0 mg/m3 TWA; Appendix A3 - Confirmed Animal Carcinogen with Unknown Relevance to Humans
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Limit (REL): 5 mg/m3 TWA; 10 mg/m3 STEL; Appendix A - NIOSH Potential Occupational Carcinogens (REL listed under Di-sec octyl phthalate)
Di-(2-Ethylhexyl)phthalate (DEHP) is an OSHA Select Carcinogen. However, the mechanisms of carcinogenesis (liver tumors) in rats and mice may not be relevant to human exposures.
Endocrine disrupting effects in rats including loss of spermatogenesis in males and anovulation in females, as well as teratogenicity in offspring, have been reported. However, evidence is lacking to indicate that DEHP-induced developmental and reproductive toxicity observed in animals (both sexes) can occur in humans.
DEHP-metabolizing enzymes include lipase, alcohol dehydrogenase, aldehyde dehydrogenase, UDP-glucuronyl transferase, and the cytochrome P450 system.
Five metabolites were quantified in urine after oral administration of labeled DEHP to a human volunteer, who excreted about 75% of the dose in urine in 44 hours. The most abundant metabolite was mono(2-ethyl-5-hydroxyhexyl)phthalate (24% of the dose).
EPA's oral reference dose (daily oral exposure likely to be without an appreciable risk of deleterious effects during a lifetime) for DEHP is 0.02 mg/kg/day.
Foster, P.M.D., Mylchreest, E., Guido, K.W. and Sar, M.: Effects of phthalate esters on the developing reproductive tract of male rats. Human Reprod. Update 7(3): 231-235, 2001.
Koch, H.M., Bolt, H.M., Preuss, R. and Angerer, J.: New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP. Arch. Toxicol. 79(7): 367-376, 2005.
Lovekamp-Swan, T. and Davis, B.J.: Mechanisms of phthalate ester toxicity in the female reproductive system. Environ. Health Perspect. 111(2): 139-145, 2003.
Pohanish, R.P. (editor): Di(2-Ethylhexyl)phthalate. In, Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, Fourth Ed., Vol. 1. Norwich, NY: Noyes Publications, William Andrew Publishing, 2002, pp. 873-876.
Shea, K.M. and American Academy of Pediatrics Committee on Environmental Health. Pediatric exposure and potential toxicity of phthalate plasticizers. Pediatrics 111(6 Pt. 1): 1467-1474, 2003.
Tickner, J.A., Schettler, T., Guidotti, T., McCally, M. and Rossi, M.: Health risks posed by use of di-2-ethyhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am. J. Ind. Med. 39(1): 100-111, 2001.
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