Notice of Addition of Documents and Information to Rulemaking File, Amendment to Section 12805: MADL for DEHP by Oral Exposure

Go to downloads

Pursuant to the requirements of Government Code sections 11346.8(d), 11346.9(a)(1), and 11347.1, the Office of Environmental Health Hazard Assessment (OEHHA) is providing notice that documents and other information which the agency has relied upon in proposing amendments to Title 22, California Code of Regulations, section 12805, have been added to the rulemaking file and are available for public inspection and comment.

The purpose of this notice is to enter all relevant documents into the Rulemaking File, OAL File No. Z-05-0614-06. All the documents included in this notice had not been previously included in the Rulemaking File, OAL File No. Z-05-0614-06, but have been considered by OEHHA in establishing the proposed maximum allowable dose levels (MADLs) for DEHP by oral exposure. Of these documents, one is the revised draft OEHHA document supporting the proposed MADLs for DEHP by oral exposure (OEHHA, 2006), two others (Koch et al., 2003 and Stedman’s Medical Dictionary, 27th edition, 2003) are cited in the revised draft MADL document (OEHHA, 2006) and listed in the References section of this document.

All other documents on the list below have been identified in the Bibliography section of the revised draft OEHHA document supporting proposed MADLs for DEHP by oral exposure (OEHHA, 2006). All the documents identified in the Bibliography section of the document have been considered by OEHHA staff but did not directly contribute to the development of the MADLs and were not cited in the main text in the OEHHA (2006) MADL document. Thus, these papers are sources of potentially relevant information. Some documents identified in this notice are research or review papers that became available to OEHHA after preparation of the draft MADL document was completed and released to the public for comment on June 24, 2005. OEHHA staff reviewed these papers as they became available, and determined that no substantial revision to the MADL document was necessitated by these papers.

These documents are available for inspection at the OEHHA’s office located at 1001 “I” Street, 19th Floor, Sacramento, CA from May 5, 2006 through May 22, 2006, between the hours of 8:00 a.m. and 5:00 p.m. If you have any comments regarding the documents and other information, OEHHA will accept written comments between (date) and (date). All written comments must be submitted to OEHHA by e-mail, mail, fax, courier or hand-delivered, no later than 5:00 p.m. on May 22, 2006 and addressed to:

Office of Environmental Health Hazard Assessment
Street Address: 1001 I Street, 19th Floor
Sacramento, CA 95814

Mailing Address: P.O. Box 4010
Sacramento, CA 95812

Fax No.: (916) 323-8803
Telephone: (916) 445-6900

Comments transmitted via email should be addressed to: P65Public.Comments@oehha.ca.gov.

It is requested but not required that written statements or arguments be submitted in triplicate. All written comments received by May 22, 2006, which pertain to the above-listed documents and other information will be reviewed and responded to by OEHHA’s staff as part of the compilation of the rulemaking file.

Inquiries concerning the action described in this notice may be directed to OEHHA, in writing, at the address given above, or by telephone at (916) 445-6900.

Documents and information added to Notice File No. Z-05-0614-06:

Revised draft OEHHA document supporting proposed MADLs for DEHP by oral exposure:

Office of Environmental Health Hazard Assessment (OEHHA, 2006). Proposition 65 Maximum Allowable Dose Level (MADL) for Reproductive Toxicant for Di(2-ethylhexyl)phthalate (DEHP) by Oral Exposure. OEHHA Reproductive and Cancer Hazard Assessment Section, California Environmental Protection Agency, Sacramento, April.

Research papers or documents cited and listed as “References” in the OEHHA (2006) document:

Koch HM, Rossbach B, Drexler H, Angerer J (2003). Internal exposure of the general population to DEHP and other phthalates--determination of secondary and primary phthalate monoester metabolites in urine. Environ Res 93, 177-85.

Stedman's Medical Dictionary, 27th edition (2000). Pub. Lippincott Williams & Wilkins. Accessible online at http://www.stedmans.com.

Research papers or documents listed in the Bibliography in the OEHHA (2006) document:

Abbott DH, Hearn JP (1978). Physical, hormonal and behavioural aspects of sexual development in the marmoset monkey, Callithrix jacchus. J Reprod Fertil 53, 155-66.

Agarwal DK, Eustis S, Lamb JC 4th, Jameson CW, Kluwe WM (1986). Influence of dietary zinc on di(2-ethylhexyl)phthalate-induced testicular atrophy and zinc depletion in adult rats. Toxicol Appl Pharmacol 84, 12-24.

Anderson WA, Barnes KA, Castle L, Damant AP, Scotter MJ (2002). Determination of isotopically labelled monoesterphthalates in urine by high performance liquid chromatography-mass spectrometry. Analyst 127, 1193-7.

Arslan M, Weinbauer GF, Schlatt S, Shahab M, Nieschlag E (1993). FSH and testosterone, alone or in combination, initiate testicular growth and increase the number of spermatogonia and Sertoli cells in a juvenile non-human primate (Macaca mulatta). J Endocrinol 136, 235-43.

Asaoka K, Hagihara K, Kabaya H, Sakamoto Y, Katayama H, Yano K (2000). Uptake of phthalate esters, di(n-butyl)phthalate and di(2-ethylhexyl)phthalate, as environmental chemicals in monkeys in Japan. Bull Environ Contam Toxicol 64, 679-85.

Barr AB (1973). Timing of spermatogenesis in four nonhuman primate species. Fertil Steril 24, 381-9.

Behr R, Hunt N, Ivell R, Wessels J, Weinbauer GF (2000). Cloning and expression analysis of testis-specific cyclic 3', 5'-adenosine monophosphate-responsive element modulator activators in the nonhuman primate (Macaca fascicularis): comparison with other primate and rodent species. Biol Reprod 62, 1344-51.

Berensztein EB, Sciara MI, Rivarola MA, Belgorosky A (2002). Apoptosis and proliferation of human testicular somatic and germ cells during prepuberty: high rate of testicular growth in newborns mediated by decreased apoptosis. J Clin Endocrinol Metab 87, 5113-8.

Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (2000). The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54, 138-53.

Borch J, Vinggaard AM, Ladefoged O (2002). The effect of combined prenatal exposure to di(2-ethylhexyl)phthalate and di(2-ethylhexyl)adipate on testosterone production in rats. Reprod Toxicol 16(4), 406.

Borch J, Vinggaard AM, Ladefoged O (2003). The effect of combined exposure to di(2-ethylhexyl)phthalate and diisononylphthalate on testosterone production in rats. Reprod Toxicol 17(4), 487-8.

Brock JW, Caudill SP, Silva MJ, Needham LL, Hilborn ED (2002). Phthalate monoesters levels in the urine of young children. Bull Environ Contam Toxicol 68, 309-14.

Center for the Evaluation of Risks to Human Reproduction (CERHR, 2005). NTP-CERHR Expert Panel Update on the Reproductive and Developmental Toxicity of Di (2-ethylhexyl) Phthalate. National Toxicology Program, U.S. Department of Health and Human Services, Research Triangle Park, NC, November.

Chapin RE, Gray TJ, Phelps JL, Dutton SL (1988). The effects of mono-(2-ethylhexyl)-phthalate on rat Sertoli cell-enriched primary cultures. Toxicol Appl Pharmacol 92, 467-79.

Chemes HE (2001). Infancy is not a quiescent period of testicular development. Int J Androl 24, 2-7.

Clermont Y (1972). Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52, 198-236.

Colon I, Caro D, Bourdony CJ, Rosario O (2000). Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect 108, 895-900.

Cortes D, Muller J, Skakkebaek NE (1987). Proliferation of Sertoli cells during development of the human testis assessed by stereological methods. Int J Androl 10, 589-96.

Corton JC, Lapinskas PJ (2005). Peroxisome proliferator-activated receptors: mediators of phthalate ester-induced effects in the male reproductive tract? Toxicol Sci 83, 4-17.

Dalgaard M, Nellemann C, Lam HR, Sorensen IK, Ladefoged O (2001). The acute effects of mono(2-ethylhexyl)phthalate (MEHP) on testes of prepubertal Wistar rats. Toxicol Lett 122, 69-79.

Dalgaard M, Ostergaard G, Lam HR, Hansen EV, Ladefoged O (2000). Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats. Pharmacol Toxicol 86, 92-100.

David RM (2004). Commentary regarding the article by Koch et al.: an estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. Int. J. Hyg. Environ. Health, 206, 77-83 (2003). Int J Hyg Environ Health 207, 75-6; author reply 77-8.

Dhanya CR, Gayathri NS, Mithra K, Nair KV, Kurup PA (2004). Vitamin E prevents deleterious effects of di (2-ethyl hexyl) phthalate, a plasticizer used in PVC blood storage bags. Indian J Exp Biol 42, 871-5.

Dhanya CR, Indu AR, Deepadevi KV, Kurup PA (2003). Inhibition of membrane Na(+)-K+ Atpase of the brain, liver and RBC in rats administered di(2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl chloride (PVC) blood storage bags. Indian J Exp Biol 41, 814-20.

Eisler JA, Tannenbaum PL, Mann DR, Wallen K (1993). Neonatal testicular suppression with a GnRH agonist in rhesus monkeys: effects on adult endocrine function and behavior. Horm Behav 27, 551-67.

Elcombe CR, Mitchell AM (1986). Peroxisome proliferation due to di(2-ethylhexyl)
phthalate (DEHP): species differences and possible mechanisms. Environ Health Perspect 70, 211-9.

Fan LQ, You L, Brown-Borg H, Brown S, Edwards RJ , Corton JC (2004). Regulation of phase I and phase II steroid metabolism enzymes by PPARalpha activators. Toxicology 204, 109-21.

Fisher JS, Millar MR, Majdic G, Saunders PT, Fraser HM, Sharpe RM (1997 ). Immunolocalisation of oestrogen receptor-alpha within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood. J Endocrinol 153, 485-95.

Fisher JS, Turner KJ, Fraser HM, Saunders PT, Brown D, Sharpe RM (1998). Immunoexpression of aquaporin-1 in the efferent ducts of the rat and marmoset monkey during development, its modulation by estrogens, and its possible role in fluid resorption. Endocrinology 139, 3935-45.

Fisher JS (2004). Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction 127, 305-15.

Foster PM (2005). Mode of action: impaired fetal Leydig cell function--effects on male reproductive development produced by certain phthalate esters. Crit Rev Toxicol 35, 713-9.

Foster PM, Mylchreest E, Gaido KW, Sar M (2001). Effects of phthalate esters on the developing reproductive tract of male rats. Hum Reprod Update 7, 231-5.

Fouquet JP, Dang DC (1980). A comparative study of the development of the fetal testis and ovary in the monkey (Macaca fascicularis). Reprod Nutr Dev 20, 1439-59.

Fritz IB (1994). Somatic cell-germ cell relationships in mammalian testes during development and spermatogenesis. Ciba Found Symp 182, 271-4; discussion 274-81.

Fukuwatari T, Suzuki Y, Sugimoto E, Shibata K (2002). Elucidation of the toxic mechanism of the plasticizers, phthalic acid esters, putative endocrine disrupters: effects of dietary di(2-ethylhexyl)phthalate on the metabolism of tryptophan to niacin in rats. Biosci Biotechnol Biochem 66, 705-10.

Garde SV, Sheth AR, Kulkarni SA (1991a). Cellular distribution of inhibin in marmoset testes during development. Anat Rec 229, 334-8.

Garde SV, Sheth AR, Kulkarni SA (1991b). FSH in testes of marmosets during development: immunocytochemical localization and de novo biosynthesis. Anat Rec 231, 119-24.

Giammona CJ, Sawhney P, Chandrasekaran Y, Richburg JH (2002). Death receptor response in rodent testis after mono-(2-ethylhexyl) phthalate exposure. Toxicol Appl Pharmacol 185, 119-27.

Gray LE, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, Veeramachaneni DN, Wilson V, Price M, Hotchkiss A, Orlando E, Guillette L (2001). Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Update 7, 248-64.

Green R, Hauser R, Calafat AM, Weuve J, Schettler T, Ringer S, Huttner K, Hu H (2005). Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants. Environ Health Perspect 113, 1222-1225.

Gromoll J, Weinbauer GF, Skaletsky H, Schlatt S, Rocchietti-March M, Page DC, Nieschlag E (1999). The Old World monkey DAZ (Deleted in AZoospermia) gene yields insights into the evolution of the DAZ gene cluster on the human Y chromosome. Hum Mol Genet 8, 2017-24.

Gromoll J, Wistuba J, Terwort N, Godmann M, Muller T, Simoni M (2003). A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the New World monkey (Platyrrhini) lineage. Biol Reprod 69, 75-80.

Haider SG, Passia D, Treiber A, Milhorst S (1989). Description of eight phases of spermiogenesis in the marmoset testis. Acta Anat (Basel) 135, 180-4.

Haishima Y, Matsuda R, Hayashi Y, Hasegawa C, Yagami T, Tsuchiya T (2004). Risk assessment of di(2-ethylhexyl)phthalate released from PVC blood circuits during hemodialysis and pump-oxygenation therapy. Int J Pharm 274, 119-29.

Hasmall SC, James NH, Macdonald N, Soames AR, Roberts RA (2000). Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression. Arch Toxicol 74, 85-91.

Heyn R, Makabe S, Motta PM (1998). Ultrastructural dynamics of human testicular cords from 6 to 16 weeks of embryonic development. Study by transmission and high resolution scanning electron microscopy. Ital J Anat Embryol 103, 17-29.

Heyn R, Makabe S, Motta PM (2001). Ultrastructural morphodynamics of human Sertoli cells during testicular differentiation. Ital J Anat Embryol 106, 163-71.

Hodges JK, Hearn JP (1977). Effects of immunisation against luteinising hormone releasing hormone on reproduction of the marmoset monkey Callithrixjacchus. Nature 265, 746-8.

Holt WV, Moore HD (1984). Ultrastructural aspects of spermatogenesis in the common marmoset (Callithrix jacchus). J Anat 138 ( Pt 1), 175-88.

Hoppin JA (2003). Male reproductive effects of phthalates: an emerging picture. Epidemiology 14, 259-60.

Howarth JA, Price SC, Dobrota M, Kentish PA, Hinton RH (2001). Effects on male rats of di-(2-ethylhexyl) phthalate and di-n-hexylphthalate administered alone or in combination. Toxicol Lett 121, 35-43.

Hurst CH, Waxman DJ (2003). Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci 74, 297-308.

Husen B, Giebel J, Rune G (1999). Expression of the integrin subunits alpha 5, alpha 6 and beta 1 in the testes of the common marmoset. Int J Androl 22, 374-84.

Jackh R, Rhodes C, Grasso P, Carter JT (1984). Genotoxicity studies on di-(2-ethylhexyl) phthalate and adipate and toxicity studies on di-(2-ethylhexyl) phthalate in the rat and marmoset. Food Chem Toxicol 22, 151-5.

Jackson MR, Edmunds JG (1984). Morphological assessment of testicular maturity in marmosets (Callithrix jacchus). Lab Anim 18, 173-8.

Johnson L, Chaturvedi PK, Williams JD (1992). Missing generations of spermatocytes and spermatids in seminiferous epithelium contribute to low efficiency of spermatogenesis in humans. Biol Reprod 47, 1091-8.

Johnson L, Mckenzie KS, Snell JR (1996). Partial wave in human seminiferous tubules appears to be a random occurrence. Tissue Cell 28, 127-36.

Kang KS, Lee YS, Kim HS, Kim SH (2002). Di-(2-ethylhexyl) phthalate-induced cell proliferation is involved in the inhibition of gap junctional intercellular communication and blockage of apoptosis in mouse Sertoli cells. J Toxicol Environ Health A 65, 447-59.

Kasahara E, Sato EF, Miyoshi M, Konaka R, Hiramoto K, Sasaki J, Tokuda M, Nakano Y, Inoue M (2002). Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate. Biochem J 365, 849-56.

Kavlock R, Boekelheide K, Chapin R, Cunningham M, Faustman E, Foster P, Golub M, Henderson R, Hinberg I, Little R, Seed J, Shea K, Tabacova S, Tyl R, Williams P, Zacharewski T (2002). 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. Reprod Toxicol 16, 529-653.

Kelnar CJ, McKinnell C, Walker M, Morris KD, Wallace WH, Saunders PT, Fraser HM, Sharpe RM (2002). Testicular changes during infantile 'quiescence' in the marmoset and their gonadotrophin dependence: a model for investigating susceptibility of the prepubertal human testis to cancer therapy? Hum Reprod 17, 1367-78.

Keys DA, Wallace DG, Kepler TB, Conolly RB (2000). Quantitative evaluation of alternative mechanisms of blood disposition of di(n-butyl) phthalate and mono(n-butyl) phthalate in rats. Toxicol Sci 53, 173-84.

Kholkute SD, Aitken RJ, Lunn SF (1983). Plasma testosterone response to hCG stimulation in the male marmoset monkey (Callithrix jacchus jacchus). J Reprod Fertil 67, 457-63.

Kim HS, Saito K, Ishizuka M, Kazusaka A, Fujita S (2003). Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats. Arch Toxicol 77, 446-51.

Kluwe WM (1982). Overview of phthalate ester pharmacokinetics in mammalian species. Environ Health Perspect 45, 3-9.

Kubota Y, Nef S, Farmer PJ, Temelcos C, Parada LF, Hutson JM (2001 ). Leydig insulin-like hormone, gubernacular development and testicular descent. J Urol 165, 1673-5.

Kulkarni SA, Garde SV, Sheth AR (1992). Immunocytochemical localization of bioregulatory peptides in marmoset testes. Arch Androl 29, 87-102.

Kumar RA, Phillips DM (1991). Spermiation and sperm maturation in the marmoset. Anat Rec 229, 315-20.

Kuwada M, Kawashima R, Nakamura K, Kojima H, Hasumi H, Maki J, Sugano S (2002). Neonatal exposure to endocrine disruptors suppresses juvenile testis weight and steroidogenesis but spermatogenesis is considerably restored during puberty. Biochem Biophys Res Commun 295, 193-7.

Lampen A, Zimnik S, Nau H (2003). Teratogenic phthalates and metabolites activate the nuclear receptors PPARs and induce differentiation of F9 cells. Tox Appl Pharmacol 188, 14-23.

Latini G, Gallo F, De Felice C (2004). Birth characteristics and hepatoblastoma risk in young children. Cancer 101, 210.

Lee BC, Pineda JL, Spiliotis BE, Brown TJ, Bercu BB (1983). Male sexual development in the nonhuman primate. III. Sertoli cell culture and age-related differences. Biol Reprod 28, 1207-15.

Li LH, Donald JM, Golub MS (2005). Review on testicular development, structure, function, and regulation in common marmoset. Birth Defects Res B Dev Reprod Toxicol 74, 450-69.

Ljungvall K, Tienpont B, David F, Magnusson U, Torneke K (2004). Kinetics of orally administered di(2-ethylhexyl) phthalate and its metabolite, mono(2-ethylhexyl) phthalate, in male pigs. Arch Toxicol 78, 384-9.

Ljungvall K, Karlsson P, Hulten F, Madej A, Norrgren L, Einarsson S, Rodriguez-Martinez H, Magnusson U (2005). Delayed effects on plasma concentration of testosterone and testicular morphology by intramuscular low-dose di(2-ethylhexyl)phthalate or oestradiol benzoate in the prepubertal boar. Theriogenology 64, 1170-84.

Lottrup G, Andersson AM, Leffers H, Mortensen GK, Toppari J, Skakkebaek NE, Main KM (2006). Possible impact of phthalates on infant reproductive health. Int J Androl 29, 172-80.

Lovekamp-Swan T, Davis BJ (2003). Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 111, 139-45.

Lovekamp TN, Davis BJ (2001). Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicol Appl Pharmacol 172, 217-24.

Lunn SF, Cowen GM, Morris KD, Fraser HM (1992). Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey. J Endocrinol 132, 217-24.

Mann DR, Akinbami MA, Gould KG, Paul K, Wallen K (1998). Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank. J Endocrinol 156, 493-501.

Mann DR, Lunn SF, Akinbami MA, Samuel K, Waterfall M, Fraser HM (1999). Effect of neonatal treatment with a GnRH antagonist on development of the cell-mediated immune response in marmosets. Am J Reprod Immunol 42, 175-86.

Manojkumar V, Padmakumaran Nair KG, Santhosh A, Deepadevi KV, Arun P, Lakshmi LR, Kurup PA (1998). Decrease in the concentration of vitamin E in blood and tissues caused by di(2-ethylhexyl) phthalate, a commonly used plasticizer in blood storage bags and medical tubing. Vox Sang 75, 139-44.

McKee RH (2004). Phthalate exposure and early thelarche. Environ Health Perspect 112, A541-3.

McKinnell C, Saunders PT, Fraser HM, Kelnar CJ, Kivlin C, Morris KD, Sharpe RM (2001). Comparison of androgen receptor and oestrogen receptor beta immunoexpression in the testes of the common marmoset (Callithrix jacchus) from birth to adulthood: low androgen receptor immunoexpression in Sertoli cells during the neonatal increase in testosterone concentrations. Reproduction 122, 419-29.

Merkle J, Klimisch HJ, Jackh R (1988). Developmental toxicity in rats after inhalation
exposure of di-2-ethylhexylphthalate (DEHP). Toxicol Lett 42, 215-23.

Miraglia T, Telles Filho M, Branco AL (1970). The male reproductive system of the common marmoset (Callithrix jacchus). Acta Anat (Basel) 76, 594-611.

Moore NP (2000). The oestrogenic potential of the phthalate esters. Reprod Toxicol 14, 183-92.

Morrissey RE, Harris MW, Schwetz BA (1989). Developmental toxicity screen: results of rat studies with diethylhexyl phthalate and ethylene glycol monomethyl ether. Teratog Carcinog Mutagen 9, 119-29.

Murature DA, Tang SY, Steinhardt G, Dougherty RC (1987). Phthalate esters and semen quality parameters. Biomed Environ Mass Spectrom 14, 473-7.

Nagano M, McCarrey JR, Brinster RL (2001). Primate spermatogonial stem cells colonize mouse testes. Biol Reprod 64, 1409-16.

Narotsky MG, Hamby BT, Mitchell DS, Weller E, Chinchilli VM, Kavlock RJ (1995). Non-additive developmental toxicity in mixtures of trichloroethylene (TCE), di(2-ethylhexyl)phthalate (DEHP), and heptachlor (HEPT). Fundam Appl Toxicol 27, 203-216.

Nunes S, Brown C, French JA (2002). Variation in circulating and excreted estradiol associated with testicular activity in male marmosets. Am J Primatol 56, 27-42.

Ohlson CG, Hardell L (2000). Testicular cancer and occupational exposures with a focus on xenoestrogens in polyvinyl chloride plastics. Chemosphere 40, 1277-82.

Oishi S (1989). Effects of co-administration of di(2-ethylhexyl)phthalate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite. Arch Toxicol 63, 289-95.

Oishi S (1990). Effects of phthalic acid esters on testicular mitochondrial functions in the rat. Arch Toxicol 64, 143-7.

Oishi S (1993). Strain differences in susceptibility to di-2-ethylhexyl phthalate-induced testicular atrophy in mice. Toxicol Lett 66, 47-52.

Oishi S, Hiraga K (1980a). Testicular atrophy induced by phthalic acid monoesters: effects of zinc and testosterone concentrations. Toxicology 15, 197-202.

Oishi S, Hiraga K (1980b). Effect of phthalic acid esters on mouse testes. Toxicol Lett 5, 413-6.

Oishi S, Hiraga K (1983). Testicular atrophy induced by di-2-ethylhexyl phthalate: effect of zinc supplement. Toxicol Appl Pharmacol 70, 43-8.

Preslock JP, Steinberger E (1976). Pathway of testosterone biosynthesis in the testis of the marmoset Saguinus oedipus. Steroids 28, 775-84.

Preslock JP, Steinberger E (1977a). Androgen biosynthesis by marmoset testes in vitro. Gen Comp Endocrinol 31, 101-5.

Preslock JP, Steinberger E (1977b). Testicular steroidogenesis in the common marmoset, Callithrix jacchus. Biol Reprod 17, 289-93.

Preslock JP, Steinberger E (1979). Metabolism of pregnenolone and progesterone by testicular microsomes of the baboon Papio anubis and the marmoset Saguinus oedipus. J Steroid Biochem 10, 75-80.

Pretzer D, Ghaida JA, Rune GM (1994). Growth factors (EGF, IGF-I) modulate the morphological differentiation of adult marmoset (Callithrix jacchus) Sertoli cells in vitro. J Androl 15, 398-409.

Prince FP, Mann DR, Fraser HM (1998). Blockade of the hypothalamic-pituitary-testicular axis with a GnRH antagonist in the neonatal marmoset monkey: changes in Leydig cell ultrastructure. Tissue Cell 30, 651-61.

Reddy BS, Rozati R, Reddy S, Kodampur S, Reddy P, Reddy R (2006). High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: a prospective case control study. Fertil Steril 85, 775-9.

Rhodes C, Elcombe CR, Batten PL, Bratt H, Jackson SJ, Pratt IS, Orton TC (1983). The disposition of 14C-di-2-ethylhexylphthalate (DEHP) in the marmoset. Dev Toxicol Environ Sci 11, 579-81.

Richburg JH (2000). The relevance of spontaneous- and chemically-induced alterations in testicular germ cell apoptosis to toxicology. Toxicol Lett 112-113, 79-86.

Richburg JH, Boekelheide K (1996). Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes. Toxicol Appl Pharmacol 137, 42-50.

Richburg JH, Johnson KJ, Schoenfeld HA, Meistrich ML, Dix DJ (2002). Defining the cellular and molecular mechanisms of toxicant action in the testis. Toxicol Lett 135, 167-83.

Richburg JH, Nanez A, Gao H (1999). Participation of the Fas-signaling system in the initiation of germ cell apoptosis in young rat testes after exposure to mono-(2-ethylhexyl) phthalate. Toxicol Appl Pharmacol 160, 271-8.

Richburg JH, Nanez A, Williams LR, Embree ME, Boekelheide K (2000). Sensitivity of testicular germ cells to toxicant-induced apoptosis in gld mice that express a nonfunctional form of Fas ligand. Endocrinology 141, 787-93.

Roberts RA, Chevalier S, Hasmall SC, James NH, Cosulich SC, Macdonald N (2002). PPAR alpha and the regulation of cell division and apoptosis. Toxicology 181-182, 167-70.

Rozati R, Reddy PP, Reddanna P, Mujtaba R (2002). Role of environmental estrogens in the deterioration of male factor fertility. Fertil Steril 78, 1187-94.

Rune GM, de Souza P, Merker HJ (1991). Ultrastructural and histochemical characterization of marmoset (Callithrix jacchus) Leydig cells during postnatal development. Anat Embryol (Berl) 183, 179-91.

Schlatt S, Kim SS, Gosden R (2002). Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and heterotopic grafting to castrated hosts. Reproduction 124, 339-46.

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

Scientific Committee on Toxicity, Ecotoxicity, and the Environment (CSTEE, 2004). Opinion on the results of a second risk assessment of bis(2ethylhexyl) phthalate [DEHP]: human health part. Health and Consumer Protection Directorate-general, European Commission, Brussels.

Sharpe RM (2001). Hormones and testis development and the possible adverse effects of environmental chemicals. Toxicol Lett 120, 221-32.

Sharpe RM (2006). Pathways of endocrine disruption during male sexual differentiation and masculinisation. Best Pract Res Clin Endocrinol Metab 20, 91-110.

Sharpe RM, Martin B, Morris K, Greig I, McKinnell C, McNeilly AS, Walker M (2002). Infant feeding with soy formula milk: effects on the testis and on blood testosterone levels in marmoset monkeys during the period of neonatal testicular activity. Hum Reprod 17, 1692-703.

Sharpe RM, McKinnell C, Kivlin C, Fisher JS (2003). Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125, 769-84.

Sharpe RM, Fraser HM, Brougham MF, McKinnell C, Morris KD, Kelnar CJ, Wallace WH, Walker M (2003). Role of the neonatal period of pituitary-testicular activity in germ cell proliferation and differentiation in the primate testis. Hum Reprod 18, 2110-7.

Shirota M, Saito Y, Imai K, Horiuchi S, Yoshimura S, Sato M, Nagao T, Ono H, Katoh M (2005). Influence of di-(2-ethylhexyl)phthalate on fetal testicular development by oral administration to pregnant rats. J Toxicol Sci 30, 175-194.

Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, Brock JW, Needham LL, Calafat AM (2004). Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect 112, 331-8.

Smith D, Trennery P, Farningham D, Klapwijk J (2001). The selection of marmoset monkeys (Callithrix jacchus) in pharmaceutical toxicology. Lab Anim 35, 117-30.

Sonmez M, Turk G, Yuce A. (2005). The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology 63, 2063-72.

Swan SH (2003). Do environmental agents affect semen quality? Epidemiology 14, 261-2.

Tanaka T (2003). Effects of bis(2-ethylhexyl) phthalate (DEHP) on secondary sex ratio of mice in a cross-mating study. Food Chem Toxicol 41, 1429-32.

Tanaka T (2002). Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet. Food Chem Toxicol 40, 1499-506.

Tickner JA, Schettler T, Guidotti T, McCally M, Rossi M (2001). Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am J Ind Med 39, 100-11.

van Wezel AP, van Vlaardingen P, Posthumus R, Crommentuijn GH, Sijm DT (2000). Environmental risk limits for two phthalates, with special emphasis on endocrine disruptive properties. Ecotoxicol Environ Saf 46, 305-21.

Veeramachaneni DN (2000). Deteriorating trends in male reproduction: idiopathic or environmental? Anim Reprod Sci 60-61, 121-30.

Waliszewski M, Szymczynski GA (1990). Determination of phthalate esters in human semen. Andrologia 22, 69-73.

Weinbauer GF, Schubert J, Yeung CH, Rosiepen G, Nieschlag E (1998). Gonadotrophin-releasing hormone antagonist arrests premeiotic germ cell proliferation but does not inhibit meiosis in the male monkey: a quantitative analysis using 5-bromodeoxyuridine and dual parameter flow cytometry. J Endocrinol 156, 23-34.

Weinbauer GF, Aslam H, Krishnamurthy H, Brinkworth MH, Einspanier A, Hodges JK (2001). Quantitative analysis of spermatogenesis and apoptosis in the common marmoset (Callithrix jacchus) reveals high rates of spermatogonial turnover and high spermatogenic efficiency. Biol Reprod 64, 120-6.

Wolfe GW, Layton K, Nehrebeckyj L, Wang Y, Chapin R, Rousselle SD, Bishop J (2002). Reproductive effects of diethylhexylphthalate (DEHP) in Sprague-Dawley rats when assessed by the continuous breeding protocol. Toxicologist 66(1-S), 234.

Wong JS, Ye X, Muhlenkamp CR, Gill SS (2002). Effect of a peroxisome proliferator on 3 beta-hydroxysteroid dehydrogenase. Biochem Biophys Res Commun 293, 549-53.

Worrell NR, Cook WM, Thompson CA, Gray TJB (1989). Effect of mono-(2-ethlyhexyl) phthalate on the metabolism of energy-yielding substrates in rat Sertoli cell-enriched cultures. Toxi in Vitro 3, 77-81.