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. 1986 Mar;65:243–248. doi: 10.1289/ehp.8665243

Effects of phthalic acid esters (PAEs) on the neonate and aspects of teratogenic actions.

J A Thomas, D B Wienckowski, B A Gillies, M J Thomas, E J Youkilis
PMCID: PMC1474722  PMID: 3709448

Abstract

A review of the literature reveals that several different phthalic acid esters (PAEs) are capable of causing testicular damage. Phthalate-induced zinc deficiency is consistent with germinal epithelial damage. Among experimental animals, mice perhaps show the greatest sensitivity to phthalate-induced terata, but high doses/exposure are required. Little toxicologic information is available with regard to phthalate-induced effects upon the neonate.

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Selected References

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  1. Abbasi A. A., Prasad A. S., Rabbani P., DuMouchelle E. Experimental zinc deficiency in man. Effect on testicular function. J Lab Clin Med. 1980 Sep;96(3):544–550. [PubMed] [Google Scholar]
  2. Bell F. P. Effect of di-2-ethylhexyl phthalate in the female rat: inhibition of hepatic and adrenal sterologenesis in vitro. Bull Environ Contam Toxicol. 1980 Jan;24(1):54–58. doi: 10.1007/BF01608075. [DOI] [PubMed] [Google Scholar]
  3. Bell F. P. Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in mammals. Environ Health Perspect. 1982 Nov;45:41–50. doi: 10.1289/ehp.824541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell F. P., Makowske M., Schneider D., Patt C. S. Inhibition of sterologenesis in brain and liver of fetal and suckling rats from dams fed di-2-ethylhexyl phthalate plasticizer. Lipids. 1979 Apr;14(4):372–377. doi: 10.1007/BF02533420. [DOI] [PubMed] [Google Scholar]
  5. Bower R. K., Haberman S., Minton P. D. Terotogenic effects in the chick embryo caused by esters of phthalic acid. J Pharmacol Exp Ther. 1970 Feb;171(2):314–324. [PubMed] [Google Scholar]
  6. Calley D., Autian J., Guess W. L. Toxicology of a series of phthalate esters. J Pharm Sci. 1966 Feb;55(2):158–162. doi: 10.1002/jps.2600550206. [DOI] [PubMed] [Google Scholar]
  7. Cater B. R., Cook M. W., Gangolli S. D., Grasso P. Studies on dibutyl phthalate-induced testicular atrophy in the rat: effect on zinc metabolism. Toxicol Appl Pharmacol. 1977 Sep;41(3):609–618. doi: 10.1016/s0041-008x(77)80014-8. [DOI] [PubMed] [Google Scholar]
  8. Curto K. A., Thomas J. A. Comparative effects of diethylhexyl phthalate or monoethylhexyl phthalate on male mouse and rat reproductive organs. Toxicol Appl Pharmacol. 1982 Jan;62(1):121–125. doi: 10.1016/0041-008x(82)90108-9. [DOI] [PubMed] [Google Scholar]
  9. Daniel J. W. Toxicity and metabolism of phthalate esters. Clin Toxicol. 1978;13(2):257–268. doi: 10.3109/15563657808988236. [DOI] [PubMed] [Google Scholar]
  10. Dillingham E. O., Autian J. Teratogenicity, mutagenicity, and cellular toxicity of phthalate esters. Environ Health Perspect. 1973 Jan;3:81–89. doi: 10.1289/ehp.730381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foster P. M., Cook M. W., Thomas L. V., Walters D. G., Gangolli S. D. Differences in urinary metabolic profile from di-n-butyl phthalate-treated rats and hamsters. A possible explanation for species differences in susceptibility to testicular atrophy. Drug Metab Dispos. 1983 Jan-Feb;11(1):59–61. [PubMed] [Google Scholar]
  12. Foster P. M., Lake B. G., Cook M. W., Thomas L. V., Gangolli S. D. Structure-activity requirements for the induction of testicular atrophy by butyl phthalates in immature rats: effect on testicular zinc content. Adv Exp Med Biol. 1981;136(Pt A):445–452. doi: 10.1007/978-1-4757-0674-1_33. [DOI] [PubMed] [Google Scholar]
  13. Gangolli S. D. Testicular effects of phthalate esters. Environ Health Perspect. 1982 Nov;45:77–84. doi: 10.1289/ehp.824577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gray T. J., Butterworth K. R. Testicular atrophy produced by phthalate esters. Arch Toxicol Suppl. 1980;4:452–455. doi: 10.1007/978-3-642-67729-8_106. [DOI] [PubMed] [Google Scholar]
  15. HARRIS D. K. Some hazards in the manufacture and use of plastics. Br J Ind Med. 1959 Jul;16:221–229. doi: 10.1136/oem.16.3.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hillman L. S., Goodwin S. L., Sherman W. R. Identification and measurement of plasticizer in neonatal tissues after umbilical catheters and blood products. N Engl J Med. 1975 Feb 20;292(8):381–386. doi: 10.1056/NEJM197502202920801. [DOI] [PubMed] [Google Scholar]
  17. Kluwe W. M., Haseman J. K., Douglas J. F., Huff J. E. The carcinogenicity of dietary di(2-ethylhexyl) phthalate (DEHP) in Fischer 344 rats and B6C3F1 mice. J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):797–815. doi: 10.1080/15287398209530296. [DOI] [PubMed] [Google Scholar]
  18. Kluwe W. M., Haseman J. K., Huff J. E. The carcinogenicity of di(2-ethylhexyl) phthalate (DEHP) in perspective. J Toxicol Environ Health. 1983 Jul;12(1):159–169. doi: 10.1080/15287398309530414. [DOI] [PubMed] [Google Scholar]
  19. Kluwe W. M. Overview of phthalate ester pharmacokinetics in mammalian species. Environ Health Perspect. 1982 Nov;45:3–9. doi: 10.1289/ehp.82453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lewandowski M., Fernandes J., Chen T. S. Assessment of the teratogenic potential of plasma-soluble extracts of diethylhexyl phthalate plasticized polyvinyl chloride plastics in rats. Toxicol Appl Pharmacol. 1980 Jun 15;54(1):141–147. doi: 10.1016/0041-008x(80)90014-9. [DOI] [PubMed] [Google Scholar]
  21. MILLAR M. J., ELCOATE P. V., FISCHER M. I., MAWSON C. A. Effect of testosterone and gonadotrophin injections on the sex organ development of zinc-deficient male rats. Can J Biochem Physiol. 1960 Dec;38:1457–1466. [PubMed] [Google Scholar]
  22. MILLAR M. J., FISCHER M. I., ELCOATE P. V., MAWSON C. A. The effects of dietary zinc deficiency on the reproductive system of male rats. Can J Biochem Physiol. 1958 Jun;36(6):557–569. [PubMed] [Google Scholar]
  23. Nikonorow M., Mazur H., Piekacz H. Effect of orally administered plasticizers and polyvinyl chloride stabilizers in the rat. Toxicol Appl Pharmacol. 1973 Oct;26(2):253–259. doi: 10.1016/0041-008x(73)90259-7. [DOI] [PubMed] [Google Scholar]
  24. Oishi S., Hiraga K. Testicular atrophy induced by phthalic acid esters: effect on testosterone and zinc concentrations. Toxicol Appl Pharmacol. 1980 Mar 30;53(1):35–41. doi: 10.1016/0041-008x(80)90378-6. [DOI] [PubMed] [Google Scholar]
  25. Parkhie M. R., Webb M., Norcross M. A. Dimethoxyethyl phthalate: embryopathy, teratogenicity, fetal metabolism and the role of zinc in the rat. Environ Health Perspect. 1982 Nov;45:89–97. doi: 10.1289/ehp.824589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Peakall D. B. Phthalate esters: Occurrence and biological effects. Residue Rev. 1975;54:1–41. doi: 10.1007/978-1-4612-9857-1_1. [DOI] [PubMed] [Google Scholar]
  27. Protsenko E. I. O gonadotropnom deistvii ftalevogo angidrida. Gig Sanit. 1970 Jan;35(1):105–106. [PubMed] [Google Scholar]
  28. Ruddick J. A., Villeneuve D. C., Chu I., Nestmann E., Miles D. An assessment of the teratogenicity in the rat and mutagenicity in Salmonella of mono-2-ethylhexyl phthalate. Bull Environ Contam Toxicol. 1981 Aug;27(2):181–186. doi: 10.1007/BF01611005. [DOI] [PubMed] [Google Scholar]
  29. Shiota K., Chou M. J., Nishimura H. Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and di-n-buty phthalate (DBP) in mice. Environ Res. 1980 Jun;22(1):245–253. doi: 10.1016/0013-9351(80)90136-x. [DOI] [PubMed] [Google Scholar]
  30. Shiota K., Nishimura H. Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice. Environ Health Perspect. 1982 Nov;45:65–70. doi: 10.1289/ehp.824565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Singh A. R., Lawrence W. H., Autian J. Embryonic-fetal toxicity and teratogenic effects of adipic acid esters in rats. J Pharm Sci. 1973 Oct;62(10):1596–1600. doi: 10.1002/jps.2600621004. [DOI] [PubMed] [Google Scholar]
  32. Singh A. R., Lawrence W. H., Autian J. Maternal-fetal transfer of 14C-di-2-ethylhexyl phthalate and 14C-diethyl phthalate in rats. J Pharm Sci. 1975 Aug;64(8):1347–1350. doi: 10.1002/jps.2600640819. [DOI] [PubMed] [Google Scholar]
  33. Singh A. R., Lawrence W. H., Autian J. Mutagenic and antifertility sensitivities of mice to di-2-ethylhexyl phthalate (DEHP) and dimethoxyethyl phthalate (DMEP). Toxicol Appl Pharmacol. 1974 Jul;29(1):35–46. doi: 10.1016/0041-008x(74)90159-8. [DOI] [PubMed] [Google Scholar]
  34. Singh A. R., Lawrence W. H., Autian J. Teratogenicity of phthalate esters in rats. J Pharm Sci. 1972 Jan;61(1):51–55. doi: 10.1002/jps.2600610107. [DOI] [PubMed] [Google Scholar]
  35. Thomas J. A., Schein L. G., Gupta P. K., McCafferty R. E., Felice P. R., Donovan M. P. Failure of monoethylhexyl phthalate to cause teratogenic effects in offspring of rabbits. Toxicol Appl Pharmacol. 1979 Dec;51(3):523–528. doi: 10.1016/0041-008x(79)90377-6. [DOI] [PubMed] [Google Scholar]
  36. Thomas J. A., Thomas M. J. Biological effects of di-(2-ethylhexyl) phthalate and other phthalic acid esters. Crit Rev Toxicol. 1984;13(4):283–317. doi: 10.3109/10408448409023761. [DOI] [PubMed] [Google Scholar]
  37. Tomita I., Nakamura Y., Yagi Y., Tutikawa K. Fetotoxic effects of mono-2-ethylhexyl phthalate (MEHP) in mice. Environ Health Perspect. 1986 Mar;65:249–254. doi: 10.1289/ehp.8665249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tomita I., Nakamura Y., Yagi Y., Tutikawa K. Teratogenicity/fetotoxicity of DEHP in mice. Environ Health Perspect. 1982 Nov;45:71–75. doi: 10.1289/ehp.824571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Verrett M. J., Mutchler M. K., Scott W. F., Reynaldo E. F., McLaughlin J. Teratogenic effects of captan and related compounds in the developing chicken embryo. Ann N Y Acad Sci. 1969;160(1):334–343. doi: 10.1111/j.1749-6632.1969.tb15853.x. [DOI] [PubMed] [Google Scholar]
  40. Wuest H. M., Fox R. R., Crary D. D. Relationship between teratogeny and structure in the thalidomide field. Experientia. 1968 Oct 15;24(10):993–994. doi: 10.1007/BF02138700. [DOI] [PubMed] [Google Scholar]
  41. Yagi Y., Nakamura Y., Tomita I., Tsuchikawa K., Shimoi N. Teratogenic potential of di- and mono-(2-ethylhexyl)phthalate in mice. J Environ Pathol Toxicol. 1980 Sep;4(2-3):533–544. [PubMed] [Google Scholar]

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