Andersen ME (1981) Saturable metabolism and its relationship to toxicity. Crit Rev Toxicol 9:105–150
Andersen ME (2022) Assessing modes of action, measures of tissue dose and human relevance of rodent toxicity endpoints with octamethylcyclotetrasiloxane (D4). Toxicol Lett 357:57–72. https://doi.org/10.1016/j.toxlet.2021.12.020
Andersen ME, Sarangapani R, Reitz RH, Gallavan RH, Dobrev ID, Plotzke KP (2001) Physiological modeling reveals novel pharmacokinetic behavior for inhaled octamethylcyclotetrasiloxane in rats. Toxicol Sci 60(2):214–231
Atkinson HC, Stanescu I, Frampton C, Salem II, Beasley CP, Robson R (2015) Pharmacokinetics and bioavailability of a fixed-dose combination of ibuprofen and paracetamol after intravenous and oral administration. Clin Drug Investig 35(10):625–632
Article PubMed PubMed Central Google Scholar
Baker S (2010) Potential for octamethylcyclotetrasiloxane and decamethylcyclopentasiloxane to interact with and activate the dopamine D2 receptor in rat striatal membranes. Silicones Environmental, Health and Safety Council Report
Borgert CJ, Quill TF, McCarty LS, Mason AM (2004) Can mode of action predict mixture toxicity for risk assessment? Toxicol Appl Pharmacol 201(2):85–96. https://doi.org/10.1016/j.taap.2004.05.005
Borgert CJ, Wise K, Becker RA (2015) Modernizing problem formulation for risk assessment necessitates articulation of mode of action. Regul Toxicol Pharmacol 72(3):538–551
Borgert CJ, Matthews JC, Baker SP (2018) Human-relevant potency threshold (HRPT) for ERα agonism. Arch Toxicol 92(5):1685–1702. https://doi.org/10.1007/s00204-018-2186-z
Article PubMed PubMed Central Google Scholar
Borgert CJ, Fuentes C, Burgoon LD (2021) Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety. Arch Toxicol 95(12):3651–3664. https://doi.org/10.1007/s00204-021-03155-4
Article PubMed PubMed Central Google Scholar
Borgert CJ, Burgoon LD, Matthews JC (2024) The physiological and biochemical basis of potency thresholds modeled using human estrogen receptor alpha: implications for identifying endocrine disruptors. Arch Toxicol 98(6):1795–1807. https://doi.org/10.1007/s00204-024-03723-4
Article PubMed PubMed Central Google Scholar
Borgert CJ, Burgoon LD (2024) Octamethylcyclotetrasiloxane (D4) lacks endocrine disruptive potential via estrogen pathways. Archives Toxicol (in press)
Burgoon LD, Fuentes C, Borgert CJ (2022) A novel approach to calculating the kinetically derived maximum dose. Arch Toxicol 96:809–816
Article PubMed PubMed Central Google Scholar
Burgoon LD, Borgert CJ, Fuentes C, Klaunig JE (2023) Kinetically-derived maximal dose (KMD) indicates lack of human carcinogenicity of ethylbenzene. Arch Toxicol. https://doi.org/10.1007/s00204-023-03629-7
Article PubMed PubMed Central Google Scholar
Burns-Naas LA, Meeks RG, Kolesar GB, Mast RW, Elwell MR, Hardisty JF, Thevenaz P (2002) Inhalation toxicology of octamethylcyclotetrasiloxane (D4) following a 3-month nose-only exposure in Fischer 344 rats. Int J Toxicol 21(1):39–53
Bus JS (2017) “The dose makes the poison”: key implications for mode of action (mechanistic) research in a 21st century toxicology paradigm. Curr Opin Toxicol 3:87–91
Campbell JL Jr, Andersen ME, Van Landingham C, Gentry PR, Jensen E, Domoradzki JY, Clewell HJ III (2017) Refinement of the oral exposure description in the cyclic siloxane PBPK model for rats and humans: implications for exposure assessment. Toxicol Lett 279(Suppl 1):125–135. https://doi.org/10.1016/j.toxlet.2017.04.002
Campbell J, Andersen M, Gentry R, Landingham CV, Clewell H (2023) Incorporation of a recirculating mobile lipid pool description into the cyclic volatile siloxane (cVMS) PBPK model captures terminal clearance of D4 after repeated inhalation exposure in F344 and SD Rats. Toxicol Lett 375:29–38
Carr CJ, Kolbye AC (1991) A critique of the use of the maximum tolerated dose in bioassays to assess cancer risks from chemicals. Regul Toxicol Pharmacol 14(1):78–87
Christiansen S, Draskau MK, Svingen T, Axelstad M (2022) Hazard assessment of endocrine disruptors—assessment of D4. Danish centre on endocrine disrputors, National Food Institute, Technical University of Denmark. https://edlists.org/sites/edlists.org/files/media/document/D4HazzardAssessment2022.pdf
Dekant W, Bridges J, Scialli AR (2017a) A quantitative weight of evidence assessment of confidence in modes-of-action and their human relevance. Regul Toxicol Pharmacol 90:51–71. https://doi.org/10.1016/j.yrtph.2017.08.012
Dekant W, Scialli AR, Plotzke K, Klaunig JE (2017b) Biological relevance of effects following chronic administration of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats. Toxicol Lett 279(Suppl 1):42–53. https://doi.org/10.1016/j.toxlet.2017.01.010
Dobrev ID, Nong A, Liao KH, Reddy MB, Plotzke KP, Andersen ME (2008) Assessing kinetic determinants for metabolism and oral uptake of octamethylcyclotetrasiloxane (D4) from inhalation chamber studies. Inhal Toxicol 20(4):361–373
Domoradzki JY, Sushynski CM, Sushynski JM, McNett DA, Van Landingham C, Plotzke KP (2017) Metabolism and disposition of [14C]-methylcyclosiloxanes in rats. Toxicol Lett 279(Suppl 1):98–114
Fisher JW (2003) PBPK modeling advances understanding of D4 pharmacokinetics. Toxicol Sci 72(1):1–2
Franzen A, Greene T, Van Landingham C, Gentry R (2017) Toxicology of octamethylcyclotetrasiloxane (D4). Toxicol Lett 279(Suppl 1):2–22. https://doi.org/10.1016/j.toxlet.2017.06.007
Gentry R, Franzen A, Van Landingham C, Greene T, Plotzke K (2017) A global human health risk assessment for octamethylcyclotetrasiloxane (D4). Toxicol Lett 279(Suppl 1):23–41. https://doi.org/10.1016/j.toxlet.2017.05.019.Jean
A Isquith (1982) Evaluation of the D4 in the rodent dominant lethal test. Dow corning corporation toxicology department, Report No.: 1982–10005–1029, as cited in REACH 2011.
Isquith A, Matheson D, Slesinski R (1988a) Genotoxicity studies on selected organosilicon compounds: in vitro assays. Food Chem Toxicol 26:255–261
Isquith A, Slesinski R, Matheson D (1988b) Genotoxicity studies on selected organosilicon compounds: in vivo assays. Food Chem Toxicol 26:263–266
Jean PA, Plotzke KP (2017) Chronic toxicity and oncogenicity of octamethylcyclotetrasiloxane (D4) in the Fischer 344 rat. Toxicol Lett 279(Suppl 1):75–97. https://doi.org/10.1016/j.toxlet.2017.06.003
Jean PA, Sloter ED, Plotzke KP (2017) Effects of chronic exposure to octamethylcyclotetrasiloxane and decamethylcyclopentasiloxane in the aging female Fischer 344 rat. Toxicol Lett 279(Suppl 1):54–74. https://doi.org/10.1016/j.toxlet.2017.08.016
Jovanovic ML, McMahon JM, McNett DA, Tobin JM, Plotzke KP (2008) In vitro and In vivo percutaneous absorption of 14C-octamethylcyclotetrasiloxane (14C–D4) and 14C-decamethylcyclopentasiloxane (14C–D5). Regul Toxicol Pharmacol 50(2):239–248
Juan-Colás J, Dresser L, Morris K, Lagadou H, Ward RH, Burns A, Tear S, Johnson S, Leake MC, Quinn SD (2020) The mechanism of vesicle solubilization by the detergent sodium dodecyl sulfate. Langmuir 36(39):11499–11507. https://doi.org/10.1021/acs.langmuir.0c01810
Luu HM, Hutter JC (2001) Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation. Environ Health Perspect 109(11):1095–1101
PubMed PubMed Central Google Scholar
MS Marty, MP Bell, F Zhang (2019) Octamethylcyclotetrasiloxane (D4): toxicokinetic study in estrous cycle staged non-pregnant Crl: CD(SD) rats following repeated inhalation exposure. The Dow Chemical Company Study ID: 171006. Midland, MI.
Matthews JC (2021) A mechanistic evaluation of the potential for octamethylcyclotetrasiloxane to produce effects via endocrine modes of action. Crit Rev Toxicol 51(7):571–590. https://doi.org/10.1080/10408444.2021.1994525
McFadden LG, Bartels MJ, Rick DL, Price PS, Fontaine DD, Saghir SS (2012) Statistical methodology to determine kinetically derived maximum tolerated dose in repeat dose toxicity studies. Reg Toxicol Pharmacol 63:344–351
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