Joseph F. Holson

Last updated
Joseph F. Holson
Born
Joseph Franklin Holson
NationalityAmerican
Other namesJoe Holson
Alma mater East Carolina University
University of Cincinnati College of Medicine
Scientific career
Fields Toxicologist
Institutions National Center for Toxicological Research
WIL Research Laboratories
Thesis Relative Transport Roles of Chorioallantic and Yolk Sac Placentae on the 12th and 13th Days of Gestation  (1974)
Doctoral advisor James G. Wilson

Joseph F. Holson, an American scientist, business executive, and educator in the disciplines of toxicology and product development, served as President of WIL Research Laboratories for 20 years (1988-2008). He is known for his contributions to the fields of developmental and reproductive toxicology (DART), [1] pharmacokinetics, [2] [3] and risk assessment, [4] including extensive experience with study design, data interpretation, [1] [5] and interspecies extrapolation of health effects data. [6] [7] He has served in numerous U.S. EPA/FDA advisory committees and as an expert toxicology witness. He was elected to two National Academy of Sciences toxicology committees. [8] [9] Dr. Holson is an editor and author of the textbook Regulatory Toxicology [10] and an author of two significant chapters in the textbook Developmental and Reproductive Toxicology: A Practical Approach, Second Edition. [1] [5] Two of his peer-reviewed articles were recognized by the Risk Assessment Specialty Section of the Society of Toxicology as the Outstanding Published Papers Demonstrating an Application of Risk Assessment. [3] [4] He is the first author to receive this award in consecutive years for publications produced with two separate sets of coauthors.

Contents

Education

Joseph Holson received his Doctorate in Physiology in 1973 from the University of Cincinnati College of Medicine, having studied under the direction of Dr. James G. Wilson in the disciplines of developmental toxicology and research pediatrics. His doctoral research investigated the relative transport capabilities of chorioallantoic and yolk sac placentae during organogenesis in the rat. [11] Prior to his doctoral training, he earned a B.S. (1967) and M.S. (1969) [12] in Biology from East Carolina University (receiving the Poteat Award for his research on the teratogenicity of LSD). [13] He also completed a Traineeship in Reproductive Physiology at Louisiana State University in Baton Rouge, Louisiana, in 1970.

Career

National Center for Toxicological Research

Dr. Holson began his professional career in 1973 with the U.S. FDA/EPA-sponsored National Center for Toxicological Research (NCTR) in Little Rock, Arkansas, as a reproductive toxicologist. He became the Division Director in 1975 and organized a multidisciplinary research program, [14] which became one of the nation's major federally sponsored research groups in reproductive toxicology. For the next five years, he directed the teratology and developmental toxicology research programs of the National Toxicology Program (NTP), which focused on biochemical and physiological causes of birth defects, pharmacokinetics, postnatal functional evaluations, and mechanistic studies. While at NCTR, Holson also was instrumental in developing the FDA Good Laboratory Practice (GLP) regulations and organized and wrote the first FDA training program for GLP inspectors.

During his tenure at NCTR, he also served as Assistant Professor of Physiology in the Interdisciplinary Toxicology Training Program at the University of Arkansas School of Medicine in Little Rock, Arkansas. In this capacity, he developed and taught the first graduate-level regulatory toxicology course in the country, served on PhD student committees, and was a member of the admissions committee and policy council.

Science Applications International Corporation

Dr. Holson joined Science Applications International Corporation (SAIC) in La Jolla, California during March 1980 to establish research and development and chemical testing programs in toxicology. For the next five years, he directed SAIC’s toxicology division, which included an active reproductive toxicology research emphasis. In 1983, he was elected to SAIC's Executive Science and Technology Council. During his time at SAIC, he served as an adjunct lecturer in toxicology for the Toxicology Training Program at the University of Arizona and the Graduate Program in Public Health at San Diego State University.

Biomedical Research Institute of America

From 1985 through 1986, he served as President of Biomedical Research Institute of America in La Jolla, California and as an independent consultant in toxicology. From 1980-1986, he also served as a member of the Board of Directors and Secretary for the San Diego Biomedical Research Institute.

WIL Research Laboratories

In March 1987, Dr. Holson was appointed Vice President and Director of Developmental and Reproductive Toxicology at WIL Research Laboratories, Inc., in Ashland, Ohio. In August 1988, he was promoted to President and Director of WIL Research. During the next 20 years, he was responsible for all fiduciary and scientific aspects of the company’s operations. [15] He remained scientifically active by serving as a study director upon special request, selectively reviewing data and reports, advising sponsors regarding toxicologic and product development issues, serving as a consultant to federal agencies, publishing scientific papers, giving presentations to various community and scientific organizations, and lecturing at Ashland University. He also served on Ashland University’s Science Advisory Board (1990-2008) and Board of Trustees (1993-1998), as well as Pfizer's Advisory Panel for Developmental and Reproductive Toxicology and Johnson & Johnson's Advisory Panel for Pediatric-Approved Pharmaceuticals.

Under Joe Holson's leadership, WIL Research grew from approximately 30 employees and negative profitability into a dynamic contract research organization employing more than 600 individuals, with an 18% compound annual growth rate and nearly $40 million annual EBITDA. This success was attributed to the internationally recognized scientific prowess of WIL's staff, the company's study director-centric business model (which viewed each study director as an individual business unit with scientific, project management, and marketing responsibilities), and internally developed innovations such as the industry's first protocol-driven toxicology data management software system. [16] Holson emphasized direct scientist-to-scientist interaction as much as possible across the entire scope of each project, which gained WIL Research numerous accolades from its clients. [17]

After nearly two decades of sustained organic growth, Holson led WIL Research through a period of private capital-financed expansion, beginning with a management buyout (in partnership with Behrman Capital [18] ) and formation of a holding company (WRH) in 2004. The expansion continued with acquisitions in the U.S. and Europe, [19] culminating in the $500 million sale of WRH to American Capital, Ltd. (NASDAQ:ACAS) in 2007. After the sale to ACAS, he served as Vice President and Chief Scientific Officer of the global entity while continuing to serve as President and Director of WIL Research Laboratories in Ashland, Ohio until his retirement from active management duties in November 2008. He served on the Board of Directors of WRH from its inception in 2004 until February 2009.

Research highlights

Joe Holson's research career has spanned a diverse range of test agents using a variety of experimental animal models and human studies. Building upon the foundational principles of teratology expounded upon by his doctoral advisor, James G. Wilson, his work has emphasized comparative and holistic approaches to problem-solving in the field of developmental and reproductive toxicology. These approaches included extensive collaboration between experimental toxicologists and epidemiologists, advancements in experimental design (e.g., use of replicates and unbalanced study designs) and biostatistics (e.g., use of statistical power calculations), and robust assessments of reliability and animal-human concordance of experimental toxicity findings. [8]

Early in Holson's career, while at NCTR, he led studies that assessed the developmental toxicity of FD&C Red No. 2, [20] [21] [22] an amaranth dye, and the herbicide 2,4,5‐T (a component of Agent Orange). [23] [24] [25] The FD&C Red No. 2 study was a multi-laboratory collaborative effort between industry, U.S. FDA, and NCTR, while the 2,4,5-T study was a large-scale multireplicated study in various strains/stocks of mice that included replicated test groups, at least four dose levels per replicate, use of multiple stocks/strains of animals to obtain an estimate of the range in sensitivities due to genotype, complete maternal pathology, and fetal histopathology and teratological evaluation. In a follow-up statistical analysis of these data, it was calculated that 805 litters per dose group would be necessary to detect a 5% increase in embryo resorption, suggesting that no standard regulatory study is adequately capable of evaluating the dose-response threshold at low response rates. [26] [27] Based on these results, Holson recommended that U.S. FDA include a similar approach to standardize the statistical resolving power of tests relative to known interlaboratory and interspecies endpoint variability and variances. [26]

Holson was also among the first developmental toxicologists to quantitatively evaluate the "litter effect" of studies in which fetal endpoints were assessed after the maternal animal was dosed. [28] Although litter-based statistical analyses had been conducted for body weight and survival parameters, Holson insisted that litter-based corrections should also be used for fetal malformations and variations. [1]

Based on his early work, Holson was among the first teratology researchers to assert that the various endpoints of developmental toxicity studies (intrauterine growth retardation, malformations [birth defects], functional impairment, and death) in fact constituted a continuum of responses rather than discrete outcomes, which led him to conclude that human manifestations of teratogenicity across exposure levels were most commonly multiple outcomes. [1] [7] Throughout his career Holson argued consistently that developmental toxicity must be viewed holistically, not simply as a group of disparate anatomical, functional, and postnatal defects, before such data can be effectively used to derive a complete estimate of human risks.

Holson was among the first to recognize that more emphasis needed to be placed on pharmacokinetic evaluations within developmental and reproductive toxicity studies in order to quantify the internal exposure to xenobiotics. [7] His team at NCTR conducted the first series of studies designed to assess the feasibility of using pharmacokinetics to improve the design, interpretation, and extrapolation of developmental toxicity studies, in an attempt to develop methods for predicting the magnitude of endpoints in teratology and to show how interlitter variability and inter-strain and inter-species differences could be better interpreted and accounted for based on differences in the handling of a compound. Throughout his career he emphasized the use of pharmacokinetic determinations as a necessary component of developmental, reproductive, and nonclinical juvenile toxicity studies. [1] [5]

Holson was also the first to apply the principle of comparative ontogeny of development (physiologic age) between organ systems in various species to the interpretation of developmental, reproductive, and pediatric toxicology data. [1] [5]

Throughout his career, Holson served as a key advisor to numerous product development programs (INDs, NDAs, TCSA consent orders, FIFRA registrations and international product registrations) and was the principal investigator in more than 600 safety assessment studies. In these studies he emphasized his longstanding principles of holistic evaluation of data, inclusion of pharmacokinetic endpoints where possible, robust and creative experimental designs, determination of the statistical power of the study relative to known variability in endpoints, and cognizance of comparative ontogeny of development. [1] [5] In addition to LSD, FD&C Red No. 2, and 2,4,5-T, he was instrumental in significant developmental, reproductive, and/or nonclinical juvenile toxicity assessments of mirex, [2] [29] inorganic arsenic, [4] [30] [31] [32] [33] [34] [35] [36] [37] nelfinavir (Viracept, an antiretroviral drug used to treat AIDS), [38] [39] fluoxetine (Prozac), [40] [41] two silicon-based ingredients found in breast implants and numerous personal care products (D4 and D5), [42] [43] [44] methyl iodide, [45] [46] and HBOC-201 (a bovine hemoglobin-based oxygen carrier). [47] [48] [49]

Retirement

After retiring from active duties at WIL Research, Dr. Holson focused on conservation efforts on his 90-acre farm outside Ashland, Ohio. Since 1994, when he began to plant native prairie grasses and several thousand trees, he allowed the bulk of the property to gradually return to a natural state as a conservation habitat supported by Ohio's Conservation Reserve Program, including development of a 10-acre wildflower area designated as a pollinator habitat. He also maintains 45 acres of mature hardwood forest. This overall effort has facilitated Holson's personal study of conservation and animal behavior, including various flora and fauna.

Felony Drug & Sex Offender Charges

In August 2009, Dr. Holson plead guilty to the "possession of cocaine and complicity involving the illegal use of a minor in nudity-oriented material or performance", [50] which required him to register as a Tier I sex offender. He later unsuccessfully appealed to withdraw these pleas. [51]

Footnotes

  1. 1 2 3 4 5 6 7 8 Holson, Joseph F.; Nemec, Mark D.; Stump, Donald G.; Kaufman, Lewis E.; Lindstrom, Pia; Varsho, Bennett J. (2006). "Significance, Reliability, and Interpretation of Developmental and Reproductive Toxicity Study Findings". In Hood, R.D. (ed.). Developmental and Reproductive Toxicology: A Practical Approach, Second Edition. Boca Raton: Taylor and Francis. pp. 329–424. ISBN   9781420040548.
  2. 1 2 Byrd, Richard A.; Young, John F.; Kimmel, Carole A.; Morris, Manford D.; Holson, Joseph F. (1982-11-01). "Computer simulation of mirex pharmacokinetics in the rat". Toxicology and Applied Pharmacology. 66 (2): 182–192. doi:10.1016/0041-008X(82)90283-6. PMID   7164097.
  3. 1 2 Sweeney, L. M.; Tyler, T. R.; Kirman, C. R.; Corley, R. A.; Reitz, R. H.; Paustenbach, D. J.; Holson, J. F.; Whorton, M. D.; Thompson, K. M. (2001-07-01). "Proposed Occupational Exposure Limits for Select Ethylene Glycol Ethers Using PBPK Models and Monte Carlo Simulations". Toxicological Sciences. 62 (1): 124–139. doi: 10.1093/toxsci/62.1.124 . ISSN   1096-6080. PMID   11399800.
  4. 1 2 3 Holson, Joseph F.; Desesso, John M.; Jacobson, Catherine F.; Farr, Craig H. (2000-07-01). "Appropriate use of animal models in the assessment of risk during prenatal development: An illustration using inorganic arsenic". Teratology. 62 (1): 51–71. doi:10.1002/1096-9926(200007)62:1<51::aid-tera10>3.3.co;2-k. ISSN   1096-9926. PMID   10861633.
  5. 1 2 3 4 5 Beck, Melissa J.; Padgett, Eric L.; Bowman, Christopher J.; Wilson, Daniel T.; Kaufman, Lewis E.; Varsho, Bennett J.; Stump, Donald G.; Nemec, Mark D.; Holson, Joseph F. (2006). "Nonclinical Juvenile Toxicity Testing". In Hood, R.D. (ed.). Developmental and Reproductive Toxicology: A Practical Approach, Second Edition. Boca Raton: Taylor and Francis. pp. 263–327. ISBN   9781420040548.
  6. ↑ White, C.G.; Holson, J.F.; Young, J.F. (1981). Extrapolation Models in Teratogenesis (NCTR Final Report for Experiment No. 281). Jefferson, AR: National Center for Toxicological Research.
  7. 1 2 3 Kimmel, C.A.; Holson, J.F.; Hogue, C.J.; Carlo, G.L. (1984). Reliability of Experimental Studies for Predicting Hazards to Human Development (NCTR Final Report for Experiment No. 6015). Jefferson, AR: National Center for Toxicological Research.
  8. 1 2 NRC (National Research Council) Committee on Developmental Toxicology (E. M. Faustman, J. C. Gerhart, N. A. Brown, G. P. Daston, M. C. Fishman, J. F. Holson, H. B. W. M. Koëter, A. P. Mahowald, J. M. Manson, R. K. Miller, P. E. Mirkes, D. W. Nebert, D. M. Noden, V. E. Papaioannou, G. C. Schoenwolf, F. Welsch, W. B. Wood) (2000). Scientific Frontiers in Developmental Toxicology and Risk Assessment. National Academy Press. ISBN   978-0-309-07086-7.{{cite book}}: CS1 maint: multiple names: authors list (link)
  9. ↑ NRC (National Research Council) Subcommittee on Reproductive and Developmental Toxicology (C. A. Kimmel, G. M. Buck, M. H. Feuston, P. M. D. Foster, J. M. Friedman, J. F. Holson, C. L. Hughes, J. A. Moore, B. A. Schwetz, A. R. Scialli, W. J. Scott, C. V. Vorhees, B. R. Zirkin) (2001). Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity . National Academy Press. ISBN   978-0-309-07316-5.{{cite book}}: CS1 maint: multiple names: authors list (link)
  10. ↑ Chengelis, C.P.; Holson, J.F.; Gad, S.C., eds. (1995). Regulatory Toxicology. New York: Raven Press Ltd. ISBN   978-0781701914.
  11. ↑ Holson, Joseph (1974). Relative Transport Roles of Chorioallantic and Yolk Sac Placentae on the 12th and 13th Days of Gestation (Doctoral Dissertation). University of Cincinnati. OCLC   981288.
  12. ↑ Holson, Joseph F. (1970). Teratogenic Potential of D-Lysergic Acid Diethylamide (delysid) in the Albino Rat (Master's Thesis). East Carolina University.
  13. ↑ "Proceeding and Abstracts from the Sixty-Sixth Annual Meeting of the North Carolina Academy of Science, May 2-3, 1969, at Wilmington, N.C." Journal of the Elisha Mitchell Society. 1969. Retrieved 2 September 2015.
  14. ↑ National Research Council (1977). The National Center for Toxicological Research: The Evaluation of Its Program. National Academy of Sciences. pp. 146–147.
  15. ↑ "Nemec promoted to lead WIL Research Labs". Ashland Times. Retrieved 2017-09-11.
  16. ↑ "You're in Good Company in Ohio: Featuring WIL Research Laboratories Inc". Forbes. 18 December 1995.
  17. ↑ "WIL Research Labs to expand". Ashland Times-Gazette. 30 July 2003.
  18. ↑ https://www.sec.gov/Archives/edgar/data/43362/000110465904029322/a04-11133_1ex99di.htm [ bare URL ]
  19. ↑ "Notox acquired by WIL Research".
  20. ↑ Collins, T. F. X.; Ruggles, D. I.; Holson, J. F. Jr.; Schumacher, H.; Gaylor, D. W.; Kennedy, G. L. Jr. (1976-05-01). "Teratological evaluation of FD&C red no. 2—A collaborative government‐industry study. I. Introduction, experimental materials, and procedures". Journal of Toxicology and Environmental Health. 1 (5): 851–856. doi:10.1080/15287397609529385. ISSN   0098-4108. PMID   58068.
  21. ↑ Holson, J. F. Jr.; Schumacher, H. J.; Gaylor, D. W.; Gaines, T. B.; Collins, T. F. X. (1976-05-01). "Teratological evaluation of FD&C red no. 2—A collaborative government‐industry study. IV. NCTR's study". Journal of Toxicology and Environmental Health. 1 (5): 867–874. doi:10.1080/15287397609529388. ISSN   0098-4108. PMID   1271492.
  22. ↑ Holson, J. F. Jr.; Gaylor, D. W.; Schumacher, H. J.; Collins, T. F. X.; Ruggles, D. I.; Keplinger, M. L.; Kennedy, G. L. Jr. (1976-05-01). "Teratological evaluation of FD&C red no. 2—A collaborative government‐industry study. V. Combined findings and discussion". Journal of Toxicology and Environmental Health. 1 (5): 875–885. doi:10.1080/15287397609529389. ISSN   0098-4108. PMID   1271493.
  23. ↑ Nelson, C. J.; Holson, J. F.; Green, H. G.; Gaylor, D. W. (1979-06-01). "Retrospective study of the relationship between agricultural use of 2,4,5-T and cleft palate occurrence in Arkansas". Teratology. 19 (3): 377–383. doi:10.1002/tera.1420190315. ISSN   1096-9926. PMID   473090.
  24. ↑ Holson, J. F.; Gaines, T. B.; Nelson, C. J.; Laborde, J. B.; Gaylor, D. W.; Sheehan, D. M.; Young, J. F. (1992-08-01). "Developmental Toxicity of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) I. Multireplicated Dose-Response Studies in Four Inbred Strains and One Outbred Stock of Mice". Toxicological Sciences. 19 (2): 286–297. doi:10.1093/toxsci/19.2.286. ISSN   1096-6080. PMID   1516787.
  25. ↑ NELSON, C (1992-01-01). "Developmental toxicity of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) II. Multireplicated dose-response studies with technical and analytical grades of 2,4,5-T in four-way outcross mice". Fundamental and Applied Toxicology. 19 (2): 298–306. doi:10.1016/0272-0590(92)90164-d. PMID   1516788.
  26. 1 2 Nelson, C. J.; Holson, J. F. (1978-10-01). "Statistical analysis of teratologic data: problems and advancements". Journal of Environmental Pathology and Toxicology. 2 (1): 187–199. ISSN   0146-4779. PMID   722220.
  27. ↑ Klaassen, Curtis D., ed. (2013). Casarett & Doull's Toxicology the Basic Science of Poisons (8th ed.). McGraw-Hill Education. p. 491. ISBN   978-0-07-176923-5.
  28. ↑ Holson, J. F.; Scott, W. J.; Gaylor, D. W.; Wilson, J. G. (1976-10-01). "Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the "Litter effect"". Teratology. 14 (2): 135–141. doi:10.1002/tera.1420140204. ISSN   1096-9926. PMID   982310.
  29. ↑ Byrd, Richard A.; Kimmel, Carole A.; Morris, Manford D.; Holson, Joseph F.; Young, John F. (1981-01-01). "Altered pattern of prenatal toxicity in rats due to different treatment schedules with mirex". Toxicology and Applied Pharmacology. 60 (2): 213–219. doi:10.1016/0041-008x(91)90225-4. PMID   7281184.
  30. ↑ DeSesso, JohnM; Jacobson, CatherineF; Scialli, AnthonyR; Farr, CraigH; Holson, JosephF (1998-07-01). "An assessment of the developmental toxicity of inorganic arsenic 1". Reproductive Toxicology. 12 (4): 385–433. doi: 10.1016/S0890-6238(98)00021-5 . PMID   9717692.
  31. ↑ Nemec, MarkD; Holson, JosephF; Farr, CraigH; Hood, RonaldD (1998-11-06). "Developmental toxicity assessment of arsenic acid in mice and rabbits". Reproductive Toxicology. 12 (6): 647–658. doi:10.1016/S0890-6238(98)00053-7. PMID   9875698.
  32. ↑ Holson, J. F.; Stump, D. G.; Ulrich, C. E.; Farr, C. H. (1999-09-01). "Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats". Toxicological Sciences. 51 (1): 87–97. doi: 10.1093/toxsci/51.1.87 . ISSN   1096-6080. PMID   10496680.
  33. ↑ Holson, Joseph F.; DeSesso, John M.; Scialli, Anthony R.; Farr, Craig H. (1999-01-01). Calderon, Willard R. ChappellCharles O. AbernathyRebecca L. (ed.). Inorganic Arsenic and Prenatal Development: A Comprehensive Evaluation for Human Risk Assessment. Oxford: Elsevier Science Ltd. pp. 183–190. doi:10.1016/b978-008043648-7/50021-2. ISBN   978-0-08-043648-7.
  34. ↑ Jacobson, Catherine F.; Stump, Donald G.; Nemec, Mark D.; Holson, Joseph F.; DeSesso, John M. (1999-09-01). "Appropriate Exposure Routes and Doses in Studies Designed to Assess Developmental Toxicity: A Case Study of Inorganic Arsenic". International Journal of Toxicology. 18 (5): 361–368. doi:10.1080/109158199225279. ISSN   1091-5818. S2CID   72950627.
  35. ↑ Stump, D.g.; Holson, J.f.; Fleeman, T.l.; Nemec, M.d.; Farr, C.h. (1999-11-01). "Comparative effects of single intraperitoneal or oral doses of sodium arsenate or arsenic trioxide during in utero development". Teratology. 60 (5): 283–291. doi:10.1002/(sici)1096-9926(199911)60:5<283::aid-tera9>3.0.co;2-7. ISSN   1096-9926. PMID   10525206.
  36. ↑ Holson, J. F; Stump, D. G; Clevidence, K. J; Knapp, J. F; Farr, C. H (2000-05-01). "Evaluation of the prenatal developmental toxicity of orally administered arsenic trioxide in rats". Food and Chemical Toxicology. 38 (5): 459–466. doi:10.1016/S0278-6915(00)00015-6. PMID   10762732.
  37. ↑ Beck, B. D.; Slayton, T. M.; Farr, C. H.; Sved, D. W.; Crecelius, E. A.; Holson, J. F. (2002-04-01). "Systemic uptake of inhaled arsenic in rabbits". Human & Experimental Toxicology. 21 (4): 205–215. doi:10.1191/0960327102ht237oa. ISSN   0960-3271. PMID   12099622. S2CID   24675062.
  38. ↑ Burns-Naas, Leigh Ann; Stump, Donald G; Webber, Stephanie; Holson, Joseph F; Masarjian, Lilit; Furman, Grace; Zorbas, Mark (2003-12-01). "Absence of reproductive and developmental toxicity in rats following oral dosing with nelfinavir". Regulatory Toxicology and Pharmacology. 38 (3): 304–316. doi:10.1016/S0273-2300(03)00097-7. PMID   14623481.
  39. ↑ Burns-Naas, Leigh Ann; Webber, Stephanie; Stump, Donald G; Holson, Joseph F; Masarjian, Lilit; Zorbas, Mark (2003-12-01). "Absence of embryo-fetal toxicity in rats or rabbits following oral dosing with nelfinavir". Regulatory Toxicology and Pharmacology. 38 (3): 291–303. doi:10.1016/S0273-2300(03)00096-5. PMID   14623480.
  40. ↑ Hines, Ronald N.; Adams, Jane; Buck, Germaine M.; Faber, Willem; Holson, Joseph F.; Jacobson, Sandra W.; Keszler, Martin; McMartin, Kenneth; Segraves, Robert Taylor (2004-08-01). "NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of fluoxetine". Birth Defects Research Part B: Developmental and Reproductive Toxicology. 71 (4): 193–280. doi:10.1002/bdrb.20014. ISSN   1542-9741. PMID   15334524.
  41. ↑ "NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Fluoxetine" (PDF). Retrieved March 12, 2016.
  42. ↑ Meeks, Robert G.; Stump, Donald G.; Siddiqui, Waheed H.; Holson, Joseph F.; Plotzke, Kathleen P.; Reynolds, Vincent L. (2007-02-01). "An inhalation reproductive toxicity study of octamethylcyclotetrasiloxane (D4) in female rats using multiple and single day exposure regimens". Reproductive Toxicology. 23 (2): 192–201. doi:10.1016/j.reprotox.2006.12.005. PMID   17254748.
  43. ↑ Siddiqui, Waheed H.; Stump, Donald G.; Plotzke, Kathleen P.; Holson, Joseph F.; Meeks, Robert G. (2007-02-01). "A two-generation reproductive toxicity study of octamethylcyclotetrasiloxane (D4) in rats exposed by whole-body vapor inhalation". Reproductive Toxicology. 23 (2): 202–215. doi:10.1016/j.reprotox.2006.11.011. PMID   17223010.
  44. ↑ Siddiqui, Waheed H.; Stump, Donald G.; Reynolds, Vincent L.; Plotzke, Kathleen P.; Holson, Joseph F.; Meeks, Robert G. (2007-02-01). "A two-generation reproductive toxicity study of decamethylcyclopentasiloxane (D5) in rats exposed by whole-body vapor inhalation". Reproductive Toxicology. 23 (2): 216–225. doi:10.1016/j.reprotox.2006.11.006. PMID   17175135.
  45. ↑ Nemec, Mark; Sloter, Eddie; Stump, Donald; Holson, Joseph; Kinzell, John (2009). "Prenatal developmental toxicity studies of inhaled methyl iodide vapor in rabbits reveal a susceptible window of exposure inducing late gestational fetotoxicity". Inhalation Toxicology. 21 (6): 449–461. doi:10.1080/08958370802596876. PMID   19519146. S2CID   24014318.
  46. ↑ Sloter, Eddie; Nemec, Mark; Stump, Donald; Holson, Joseph; Kirkpatrick, Daniel; Gargas, Michael; Kinzell, John (2009). "D. Kirkpatrick, M. Gargas, J. Kinzell, Methyl iodide-induced fetal hypothyroidism implicated in late-stage fetal death in rabbits". Inhalation Toxicology. 21 (6): 462–479. doi:10.1080/08958370802596942. PMID   19519147. S2CID   37726507.
  47. ↑ Holson, Joseph F.; Stump, Donald G.; Pearce, L. Bruce; Watson, Rebecca E.; DeSesso, John M. (2005-01-01). "Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations". Critical Reviews in Toxicology. 35 (8–9): 739–745. doi:10.1080/10408440591007412. ISSN   1040-8444. PMID   16417041. S2CID   31900464.
  48. ↑ Holson, J. F.; Stump, D. G.; Pearce, L. B.; Watson, R. E.; DeSesso, J. M. (2015-04-01). "Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment". Reproductive Toxicology. 52: 101–107. doi:10.1016/j.reprotox.2015.01.006. PMID   25697570.
  49. ↑ Stump, D. G.; Holson, J. F.; Harris, C.; Pearce, L. B.; Watson, R. E.; DeSesso, J. M. (2015-04-01). "Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from impeded function of the inverted visceral yolk sac". Reproductive Toxicology. 52: 108–117. doi:10.1016/j.reprotox.2015.01.005. PMC   7127137 . PMID   25617809.
  50. ↑ "Holson v. WRH, Inc. et al". govinfo. United States Government Publishing Office (GPO). Retrieved 23 March 2020.
  51. ↑ "Holson and Pepper appeals to withdraw pleas denied". www.times-gazette.com. Retrieved 2020-03-23.

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Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but only the gray form, which has a metallic appearance, is important to industry.

<span class="mw-page-title-main">Toxicology</span> Study of substances harmful to living organisms

Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.

Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. These may include growth retardation, delayed mental development or other congenital disorders without any structural malformations. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult.

<span class="mw-page-title-main">Cypermethrin</span> Chemical compound

Cypermethrin (CP) is a synthetic pyrethroid used as an insecticide in large-scale commercial agricultural applications as well as in consumer products for domestic purposes. It behaves as a fast-acting neurotoxin in insects. It is easily degraded on soil and plants but can be effective for weeks when applied to indoor inert surfaces. Exposure to sunlight, water and oxygen will accelerate its decomposition. Cypermethrin is highly toxic to fish, bees and aquatic insects, according to the National Pesticides Telecommunications Network (NPTN). It is found in many household ant and cockroach killers, including Raid, Ortho, Combat, ant chalk, and some products of Baygon in Southeast Asia.

<span class="mw-page-title-main">Nefiracetam</span>

Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats.

<span class="mw-page-title-main">Persistent organic pollutant</span> Organic compounds that are resistant to environmental degradation

Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely affect human health and the environment around the world. Because they can be transported by wind and water, most POPs generated in one country can and do affect people and wildlife far from where they are used and released.

Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese. It was first identified in 1837 by James Couper.

<span class="mw-page-title-main">Atrazine</span> Herbicide

Atrazine is a chlorinated herbicide of the triazine class. It is used to prevent pre-emergence broadleaf weeds in crops such as maize (corn), soybean and sugarcane and on turf, such as golf courses and residential lawns. Atrazine's primary manufacturer is Syngenta and it is one of the most widely used herbicides in the United States, Canadian, and Australian agriculture. Its use was banned in the European Union in 2004, when the EU found groundwater levels exceeding the limits set by regulators, and Syngenta could not show that this could be prevented nor that these levels were safe.

<span class="mw-page-title-main">Benzyl butyl phthalate</span> Chemical compound

Benzyl butyl phthalate (BBP) is an organic compound historically used a plasticizer, but which has now been largely phased out due to health concerns. It is a phthalate ester of containing benzyl alcohol, and n-butanol tail groups. Like most phthalates, BBP is non-volatile and remains liquid over a wide range of temperatures. It was mostly used as a plasticizer for PVC, but was also a common plasticizer for PVCA and PVB.

<span class="mw-page-title-main">Uranium in the environment</span>

Uranium in the environment refers to the science of the sources, environmental behaviour, and effects of uranium on humans and other animals. Uranium is weakly radioactive and remains so because of its long physical half-life. The biological half-life for uranium is about 15 days. Normal functioning of the kidney, brain, liver, heart, and numerous other systems can be affected by uranium exposure, because uranium is a toxic metal. The use of depleted uranium (DU) in munitions is controversial because of questions about potential long-term health effects.

Patulin is an organic compound classified as a polyketide. It is a white powder soluble in acidic water and in organic solvents. It is a lactone that is heat-stable, so it is not destroyed by pasteurization or thermal denaturation. However, stability following fermentation is lessened. It is a mycotoxin produced by a variety of molds, in particular, Aspergillus and Penicillium and Byssochlamys. Most commonly found in rotting apples, the amount of patulin in apple products is generally viewed as a measure of the quality of the apples used in production. In addition, patulin has been found in other foods such as grains, fruits, and vegetables. Its presence is highly regulated.

<span class="mw-page-title-main">Reproductive toxicity</span> A hazard associated with chemical substances

Reproductive toxicity refers to the potential risk from a given chemical, physical or biologic agent to adversely affect both male and female fertility as well as offspring development. Reproductive toxicants may adversely affect sexual function, ovarian failure, fertility as well as causing developmental toxicity in the offspring. Lowered effective fertility related to reproductive toxicity relates to both male and female effects alike and is reflected in decreased sperm counts, semen quality and ovarian failure. Infertility is medically defined as a failure of a couple to conceive over the course of one year of unprotected intercourse. As many as 20% of couples experience infertility. Among men, oligospermia is defined as a paucity of viable spermatozoa in the semen, whereas azoospermia refers to the complete of absence of viable spermatozoa in the semen.

<span class="mw-page-title-main">2,3,7,8-Tetrachlorodibenzodioxin</span> Polychlorinated dibenzo-p-dioxin, chemical compound

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a polychlorinated dibenzo-p-dioxin (sometimes shortened, though inaccurately, to simply 'dioxin') with the chemical formula C12H4Cl4O2. Pure TCDD is a colorless solid with no distinguishable odor at room temperature. It is usually formed as an unwanted product in burning processes of organic materials or as a side product in organic synthesis.

Arsenic biochemistry refers to biochemical processes that can use arsenic or its compounds, such as arsenate. Arsenic is a moderately abundant element in Earth's crust, and although many arsenic compounds are often considered highly toxic to most life, a wide variety of organoarsenic compounds are produced biologically and various organic and inorganic arsenic compounds are metabolized by numerous organisms. This pattern is general for other related elements, including selenium, which can exhibit both beneficial and deleterious effects. Arsenic biochemistry has become topical since many toxic arsenic compounds are found in some aquifers, potentially affecting many millions of people via biochemical processes.

<span class="mw-page-title-main">Riddelliine</span> Chemical compound

Riddelliine is a chemical compound classified as a pyrrolizidine alkaloid. It was first isolated from Senecio riddellii and is also found in a variety of plants including Jacobaea vulgaris, Senecio vulgaris, and others plants in the genus Senecio.

<span class="mw-page-title-main">Developmental toxicity</span>

Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and is caused by environmental insult. It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception, during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.

<span class="mw-page-title-main">Toxicology of carbon nanomaterials</span> Overview of toxicology of carbon nanomaterials

Toxicology of carbon nanomaterials is the study of toxicity in carbon nanomaterials like fullerenes and carbon nanotubes.

WIL Research Laboratories, LLC was a contract research organization (CRO), privately held for 40 years, that provided product safety toxicological research, metabolism, bioanalytical, pharmacological, and formulation services to the pharmaceutical, biotechnology, chemical, agrochemical, and food products industries, as well as manufacturing support for clinical trials. WIL Research was well-known internationally in many disciplines, and considered by many industry experts to be the premier laboratory in the world for developmental and reproductive toxicology (DART).

In the realms of toxicology and pathology, the Irwin screen is utilised to determine whether the subject(s) show adverse effects from a course of pharmaceutical treatment or environmental pollution. It is an observational methodology.

<span class="mw-page-title-main">Monobenzyl phthalate</span> Chemical compound

Monobenzyl phthalate (MBzP) also known as benzene-1, 2-dicarboxylic acid is an organic compound with the condensed structural formula C6H5CH2OOCC6H4COOH. It is the major metabolite of butyl benzyl phthalate(BBP), a common plasticizer.BBP can also be metabolized into monobutyl phthalate (MBP). Like many phthalates, BBP has attracted attention as a potential endocrine disruptor.

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