Moving Upstream: A Workshop on Evaluating Adverse Upstream Endpoints for Improved Decision Making and Risk Assessment
May 16 - 17, 2007
Doubletree Hotel, Berkeley, CA
Common ways that chemicals harm fertility and reproductive health are by disrupting hormone signaling or by altering genetic orchestration of fertility and development. Recent scientific advancements make it possible to measure these physiological changes in relationship to exposure to chemicals. This information offers the opportunity to base health standards on more sensitive and protective endpoints.
This workshop discussed how the increasing array of measurable physiological changes might be considered in the context of "adversity" and in evolving approaches to hazard and risk assessment. In particular, the workshop focused on how data on precursors or upstream indicators of toxicity can be used to improve hazard identification and dose response characterizations.
The workshop was sponsored by the California Environmental Protection Agency's Office of Environmental Health Assessment, the UC San Francisco Program on Reproductive Health and the Environment, the U.S Environmental Protection Agency's National Center for Environmental Assessment and National Center for Environmental Economics, and the University of California at Berkeley Superfund Basic Research Program.
Recommended Reading for Thyroid Case Study
- Blount BC, Pirkle JL, Osterloh JD, Valentin-Blasini L, Caldwell KL. Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environ Health Perspect. 2006 Dec;114(12):1865-71.
- Crofton KM, Zoeller RT. Mode of action: neurotoxicity induced by thyroid hormone disruption during development--hearing loss resulting from exposure to PHAHs. Crit Rev Toxicol. 2005 Oct-Nov;35(8-9):757-69.
- Crofton KM, Craft ES, Hedge JM, Gennings C, Simmons JE, Carchman RA, Carter WH Jr, DeVito MJ. Thyroid-hormone-disrupting chemicals: evidence for dose-dependent additivity or synergism. Environ Health Perspect. 2005 Nov;113(11):1549-54.
- Zoeller RT, Tan SW, Tyl RW. General background on the hypothalamic-pituitary-thyroid (HPT) axis. Crit Rev Toxicol. 2007 Jan-Feb;37(1-2):11-53.
- Zoeller RT. Environmental chemicals as thyroid hormone analogues: new studies indicate that thyroid hormone receptors are targets of industrial chemicals? Mol Cell Endocrinol. 2005 Oct 20;242(1-2):10-5.
- Zoeller RT, Crofton KM. Mode of action: developmental thyroid hormone insufficiency--neurological abnormalities resulting from exposure to propylthiouracil. Crit Rev Toxicol. 2005 Oct-Nov;35(8-9):771-81.
Anti-androgen Case Study Background Literature
- Foster PM. Mode of action: impaired fetal leydig cell function--effects on male reproductive development produced by certain phthalate esters. Crit Rev Toxicol. 2005 Oct-Nov;35(8-9):713-9.
- Gray LE Jr, Wilson VS, Stoker T, Lambright C, Furr J, Noriega N, Howdeshell K, Ankley GT, Guillette L. Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int J Androl. 2006 Feb;29(1):96-104; discussion 105-8
- Howdeshell KL, Furr J, Lambright CR, Rider CV, Wilson VS, and Gray, LE Jr. Cumulative Effects of dibutyl phthalate and diethylhexyl phthalate on Male Rat Reproductive Tract Development: Altered Fetal Steroid Hormones and Genes. ToxSci Advance Access published on March 30, 2007
- Liu K, Kim P. Lehmann, Madhabananda Sar, S. Stanley Young, and Kevin W. Gaido. Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biol Reprod. 2005 Jul;73(1):180-92.
- Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, Andersson AM, Toppari J, Skakkebaek NE. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect. 2006 Feb;114(2):270-6.
- Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL; Study for Future Families Research Team. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005 Aug;113(8):1056-61.
Immunotoxicity Case Study Background Literature
- Pruett S. and Luster M.I. Immunotoxicology: Using Immunological End Points to Predict Adverse Effects. Prepared for US EPA Risk Assessment Forum Workshop “Challenges to Integrating Immunotoxicological and Microbial Risk Assessment for Susceptible Populations and Life Stages”
- Luster MI, Parks CG, Germolec DR. Interpreting Immunotoxicology Data for Risk Assessment. Immunotoxicology and Immunopharmacology. In: Lubke R, House RV, Kimber I, ed. Immunotoxicology and Immunopharmacology, Third Edition. Boca Raton, FL: Taylor & Francis; 2006: 35-48.
- Luster MI, Germolec DR, Parks CG, Blancifort L, Kashon M, Luebke, R. Are Changes in the Immune System Predictive of Clinical Diseases? In: Investigative Immunotoxicology, Tryphonas H et al., Eds. Boca Raton, FL: Taylor & Francis; 2005: ch 11.
- Weisglas-Kuperus N, Patandin S, Berbers GA, Sas TC, Mulder PG, Sauer PJ, Hooijkaas H. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Environ Health Perspect. 2000 Dec;108(12):1203-7.
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