Phthalates

Introduction

Characteristic of the Agent

Fate and Transport

Environmental Impacts

Environmental Monitoring

Exposure Pathway

Routes of Exposure

Methods for Measuring Human Exposure

Strategies for Preventing or Controlling Exposures


Harmful Effects

Dose Response

Absorption, Distribution and Metabolism

Biomarkers

Target Organs and Tissues

Mechanisms of Toxicity

Risk Assessment and Risk Management

References

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References

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II. Young, Lily Y and Carl E. Cerniglia. Microbial Transformation and Degradation of Toxic Organic Chemicals. 1995. p.319-321.

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IV. Environmental Protection Agency, Integrated Risks Information System: Di-n-Butyl Phthalate (DBP) (CASRN 84-74-2)

V. Drew, Roger. and John Frangos, Data Collation and Review of Ecological Effects of Phthalates, Australian Vinyls Corporation, November 2001

VI. Spectrum Laboratories, Chemical Fact Sheet, Diethyl Phthalate CAS # 84662)

VII. Environmental Protection Agency, Integrated Risks Information System: Di-n-Butyl Phthalate (DBP) (CASRN 84-74-2)

VIII. Spectrum Laboratories, Chemical Fact Sheet, Bis-2-ethylhexyl Phthalate (CAS # 117817)

IX. Environmental Protection Agency, Consumer Fact sheet on Di (2-ethylhexyl) phthalate, Last updated November 26, 2002, URL:

X. Report on Carcinogens, Tenth Edition; U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, December 2002.

XI. Centers for Disease Control, Phthalate Generals

XII. Green, Kenneth, Phthalates and Human Health: Demystifying the risks of Plastic-Softening Chemicals

XIII. Warhurst, Michael, Introduction to Hormone Disrupting Compounds,

XIV. Centers for Disease Control

XV. Blount, Benjamin et al, Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population, Environmental Health Perspectives, Vol. 108, Number 10, Oct 2000.

XVI. Attaining 100% DEHP Elimination in IV bags: Miller Children’s Hospital, Going Green: A Resource Kit for Pollution Prevention in Health Care,July 17, 2003

XVII. Environmental Protection Agency,

XVIII. HERE WE GO AGAIN: PHTHALATES

XIX. Lowell Report, Lowell Center for Sustainable Development Report on Phthalates.

XX. Faust, Rosemarie Ph.D. Chemical Hazard Evaluation Group Biomedical and Environmental Information Analysis Section Health Sciences Research Division Oak Ridge National Laboratory* Oak Ridge, Tennessee. TOXICITY SUMMARY FOR DIETHYL PHTHALATE May 1994.

XXI. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for diethyl phthalate (update). Atlanta, GA.: U.S. Department of Health and Human Services, Public Health Service.

XXII. Merkle J, Klimisch H-J, Jackh R. 1988. Developmental toxicity in rats after inhalation exposure of di-2-ethylhexylphthalate (DEHP). Toxicol Lett 42:215-223.

XXIII. Schmezer P, Pool BL, Komitowski D, et al. 1988. Various short-term assays and two long-term studies with the plasticizer di(2-ethylhexyl)phthalate in the Syrian golden hamster. Carcinogenesis 9(1):37-43

XXIV. Roth, B. et al., "Di-(2-ethylhexyl)-phthalate as Plasticizer in PVC Respiratory Tubing Systems: Indications of Hazardous Effects on Pulmonary Function in Mechanically Ventilated, Preterm Infants," European Journal of Pediatrics, vol. 147 (1988), pp. 41-46.

XXV. Klimisch HJ, Hellwig J, Kaufmann W, et al. 1991. Di-(2-ethylhexyl)phthalate (DEHP): Investigation of inhalation toxicity in rats after repeated exposure (28 d). Human Exp Toxicol 10:68.

XXVI. Shaffer CB, Carpenter CP, Smyth HF. 1945. Acute and subacute toxicity of di(2-ethylhexyl)phthalate with note upon its metabolism. J Ind Hyg Toxicol 27:130-135.

XXVII. Rao MS, Yeldandi AV, Subbarao V. 1990. Quantitative analysis of hepatocellular lesions induced by di(2-ethylhexyl)phthalate in F-344 rats. J Toxicol Environ Health 30:85-89.

XXVIII. Dalton SR, Jirtle RL, Meyer SA. 2000. EGF receptors of heptaocytes from rats treated with phenobarbital in culture. Toxicol Appl Pharm. 165: 115-126.

XXIX. Gray TJ, Butterworth KR. 1980. Testicular atrophy produced by phthalate esters. Arch Toxicol (Suppl 4):452-455.

XVIII.) http://www.healthnet.sk/discussion/messages/229.html
HERE WE GO AGAIN: PHTHALATES

XIX.) Lowell Report, Lowell Center for Sustainable Development Report on Phthalates.

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XXI.) Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for diethyl phthalate (update). Atlanta, GA.: U.S. Department of Health and Human Services, Public Health Service.

XXII.) Merkle J, Klimisch H-J, Jackh R. 1988. Developmental toxicity in rats after inhalation exposure of di-2-ethylhexylphthalate (DEHP). Toxicol Lett 42:215-223.

XXIII.) Schmezer P, Pool BL, Komitowski D, et al. 1988. Various short-term assays and two long-term studies with the plasticizer di(2-ethylhexyl)phthalate in the Syrian golden hamster. Carcinogenesis 9(1):37-43

XXIV.) Roth, B. et al., "Di-(2-ethylhexyl)-phthalate as Plasticizer in PVC Respiratory Tubing Systems: Indications of Hazardous Effects on Pulmonary Function in Mechanically Ventilated, Preterm Infants," European Journal of Pediatrics, vol. 147 (1988), pp. 41-46.

XXV.) Klimisch HJ, Hellwig J, Kaufmann W, et al. 1991. Di-(2-ethylhexyl)phthalate (DEHP): Investigation of inhalation toxicity in rats after repeated exposure (28 d). Human Exp Toxicol 10:68.

XXVI.) Shaffer CB, Carpenter CP, Smyth HF. 1945. Acute and subacute toxicity of di(2-ethylhexyl)phthalate with note upon its metabolism. J Ind Hyg Toxicol 27:130-135.

XXVII.) Rao MS, Yeldandi AV, Subbarao V. 1990. Quantitative analysis of hepatocellular lesions induced by di(2-ethylhexyl)phthalate in F-344 rats. J Toxicol Environ Health 30:85-89.

XXVIII.) Dalton SR, Jirtle RL, Meyer SA. 2000. EGF receptors of heptaocytes from rats treated with phenobarbital in culture. Toxicol Appl Pharm. 165: 115-126.

XXIX.) Gray TJ, Butterworth KR. 1980. Testicular atrophy produced by phthalate esters. Arch Toxicol (Suppl 4):452-455.

XXX.) Lamb JC, Chapin RE, Teague J, et al. 1987. Reproductive effects of four phthalic acid esters in the mouse. Toxicol Appl Pharmacol 88:255-269.

XXXI.) Kurata Y, Kidachi F, Yokoyama M, et al. 1998. Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets: Lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol Sci 42:49-56.

XXXII.) Sjoberg P, Bondesson U, Gray TJ, et al. 1986b. Effects of di(2-ethylhexyl)phthalate and five of its metabolites on rat testis in vivo and in vitro. Acta Pharmacol Toxicol 58:225-233.

XXXIII) Ritter EJ, Scott WJ Jr, Randall JL, et al. 1987. Teratogenicity of di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic acid, and potentiation by caffeine. Teratology 35:41-46.

XXXIV.) Wolfgang Huber et al., "Hepatocarcinogenic Potential of Di(2-ethylhexyl)phthalate in Rodents and its Implications on Human Risk," Critical Reviews in Toxicology, vol. 26, issue 4 (June 1996).

XXXV.) Koop, Everett, Daland R. Juberg et al., A Scientific Evaluation of Health Effects of Two Plasticizers Used in Medical Devices and Toys: A Report from the American Council on Science and Health (Washington, D.C.: American Council on Science and Health, June 1999)

XXXVI.) International Agency for Research on Cancer (IARC) - Summaries & Evaluations DI(2-ETHYLHEXYL) PHTHALATE.

XXXVII.) Schmid P, Schlatter C. 1985. Excretion and metabolism of di(2-ethylhexyl)phthalate in man. Xenobiotica 15:251-256.

XXXVIII.) Rhodes C, Orton TC, Pratt IS, et al. 1986. Comparative pharmacokinetics and subacute toxicity of di(2ethylhexyl)phthalate in rats and marmosets: Extrapolation of effects in rodents to man. Environ Health Perspect 65:299-308.

XXXIX.) Albro PW. 1986. Absorption, metabolism and excretion of di(2-ethylhexyl)phthalate by rats and mice. Environ Health Perspect 65:293-298.

XL.) Short RD, Robinson EC, Lington AW, et al. 1987. Metabolic and peroxisome proliferation studies with di(2-ethylhexyl)phthalate in rats and monkeys. Toxicol Ind Health 3:185-195.

XLI.) Wester RC, Melendres J, Sedik L, et al. 1998. Percutaneous absorption of salicylic acid, theophylline, 2,4-dimethylamine, diethyl hexyl phthalic acid, and p-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicol Appl Pharmacol 151:159-165.

XLII.) Melnick RL, Morrissey RE, Tomaszewski KE. 1987. Studies by the National Toxicology Program on di(2-ethylhexyl)phthalate. Toxicol Ind Health 3:99-118.

XLIII.) Mes J, Coffin DE, Campbell DS. 1974. Di-n-butyl- and di-2-ethylhexyl phthalate in human adipose tissue. Bull Environ Contam Toxicol 12:721-725.

XLIV.) EPA. 1989. NHATS broad scan analysis: Population estimates from fiscal year 1982 specimens. Washington, DC: U.S. Environmental Protection Agency, Office of Toxic Substances. EPA 569/5-90001.

XLV.) Overturf ML, Druilhet RE, Liehr JG, et al. 1979. Phthalate esters in normal and pathological human kidneys. Bull Environ Contam Toxicol 22:536-542.

XLVI.) Dabholkar AS. 1988. Peroxisomes in the rat brain and the effects of di-(2-ethyl)hexyl phthalate during postnatal development: An electron-microscopic study. Acta Anat 131:218-221.

XLVII.) Barber ED, Fox JA, Giordano CJ. 1994. Hydrolysis, absorption and metabolism of di(2-ethylhexyl) terephthalate in the rat. Xenobiotica 24(5):441-450.

XLVIII.) Albro PW, Corbett JT. 1978. Distribution of di-mono-(II-ethylhexyl) phthalate in human plasma. Transfusion 18:750-755.

XLIX.) Albro PW, Corbett JT, Schroeder JL, et al. 1982a. Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect 45:19-25.

L.) Dostal LA, Chapin RE, Stefanski SA, et al. 1988. Testicular toxicity and reduced sertoli cell numbers in neonatal rats by di(2-ethylhexyl) phthalate and recovery of fertility as adults. Toxicol Appl Pharmacol 95:104-121.

LI.) Ganning AE, Olsson MJ, Brunk U, et al. 1991. Effects of prolonged treatment with phthalate ester on rat liver. Pharmacol Toxicol 68:392-401.

LII.) Chapin RE, Gray TJ, Phelps JL, et al. 1988. The effects of mono-(2-ethylxexyl)-phthalate on rat sertoli cell enriched primary cultures. Toxicol Appl Pharmacol 92:467-479.

LIII.) Park JD, et al. Testicular toxicity of di-(2-ethylhexyl)phthalate in young Sprague-Dawley rats. Toxicology. 2002 Feb 28;171(2-3):105-15

LIV.) Mutsuko Koizumi, Makoto Ema, Akihiko Hirose,et al. Recent studies on toxic effects of phthalate esters on reproduction and development: Focus on Di(2-ethylhexyl) phthalate and Di-n-butyl phthalate.