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1.
Figure 4

Figure 4. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

Diagnostic relationships between upstream biomarkers and adverse outcomes.

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
2.
Figure 6

Figure 6. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

Individual versus population reference range for T4: the distribution of 12 monthly measurements for 15 men compared with one individual. The distribution width for the individual is approximately one-half that of the group [adapted from Andersen et al. (2002); copyright 2002, The Endocrine Society].

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
3.
Figure 3

Figure 3. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

A combined mode-of-action model for the effects of TDCs on cancer and developmental outcomes. Abbreviations: TTR, transthyretin; UDPGT, uridine diphosphate glucuronyltransferase. Mixture models are needed to better predict effects of mixtures containing xenobiotics that affect multiple targets with common downstream effects (modified from Crofton and Zoeller 2005; U.S. EPA 2002).

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
4.
Figure 5

Figure 5. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

The predicted and empirical effects of a mixture of dioxins, furans, and PCBs on serum total T4 in rats. Predicted outcomes (additivity model) were generated using a single chemical-required additivity model. Empirical results (empirical model) showed a small but significant departure from dose additivity at the three highest mixture doses, whereas the remaining lower mixture doses were not significantly different than that predicted by additivity (modified from Crofton et al. 2005).

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
5.
Figure 1

Figure 1. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

TH control pathways and sites of disruption by xenobiotic chemicals. Abbreviations: Gluc, glucose; HO-PCBs, hydroxyl-PCBs; NIS, sodium/iodide symporter; PBDE, polybrominated diphenyl ether; PTU, propylthiouracil; T4-Gluc, T4-glucuronide; TBG, thyroid-binding globulin; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; TTR, transthyretin; UDPGT, uridine diphosphate glucuronyl-transferase. Sites or processes where xenobiotics are known or hypothesized to act as TDCs are indicated in the boxes and ovals. Xenobiotics that block, inhibit, or up -regulate these processes are shown in bold (modified from Crofton 2008).

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
6.
Figure 2

Figure 2. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

Population changes in diastolic blood pressure (A) and cholesterol (B) in relation to serum TSH or free T4, respectively. (A) Diastolic blood pressure in men and women are significantly correlated with serum TSH within the normal reference range for TSH, indicating that as serum T4 declines, diastolic blood pressure increases. (B) Serum cholesterol is negatively associated with serum free T4. An increase in free T4 by 5, 10, or 15 pmol/L would reduce LDL cholesterol by 0.13, 0.53, and 0.93 mmol/L, respectively. The data are redrawn with permission from Asvold (2007b; A) and from Razvi (2007; B) (Copyrights 2007, The Endocrine Society).

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.
7.
Figure 7

Figure 7. From: Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes.

Individual risk and mortality associated with MI. ( A ) Individual risk and prevalence for MI associated with increased serum cholesterol levels. The number above each bar represents estimate of attributable deaths per 1,000 per 10 years. Note that individual risk increases linearly (including within the range of values considered normal) but that most deaths attributable to increased cholesterol levels occur in the lower range, because this represents a greater proportion of the population (adapted from Rose 1981; with permission from the BMJ Publishing Group). (B) Death from MI associated with increased diastolic blood pressure in males 45–74 (age-adjusted rate) (adapted from U.S. EPA 1985).

Mark D. Miller, et al. Environ Health Perspect. 2009 July;117(7):1033-1041.

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