Acute PCB Benthic Invertebrate Toxicity Testing to Support the 2017 Chronic Dose‐Response Sediment Injury Model

2020 ◽  
Author(s):  
Kenneth Finkelstein ◽  
Edward F. Wirth ◽  
K.W. Chung ◽  
B.S. Shaddrix ◽  
E.C. Pisarski ◽  
...  
Keyword(s):  
Dose Response ◽  
Toxicity Testing ◽  
Benthic Invertebrate ◽  
Chronic Dose ◽  
Injury Model

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

Chronic dose‐response studies in mice fed 2‐aaf

1975 ◽  
Vol 1 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Neil A. Littlefield ◽  
Cipriano Cueto ◽  
A. Kenneth Davis ◽  
Kevin Medlock
Keyword(s):  
Dose Response ◽  
Chronic Dose

Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’

2010 ◽  
Vol 29 (1) ◽  
pp. 31-32 ◽  
Author(s):  
William J Waddell
Keyword(s):  
21St Century ◽  
Dose Response ◽  
Toxicity Testing ◽  
Pbpk Modeling ◽  
In Vitro Testing ◽  
Additional Observation ◽  
National Academy Of Sciences ◽  
Big Picture ◽  
Academy Of Sciences

The report of the National Academy of Sciences entitled ‘Toxicity Testing in the 21st Century: A Vision and a Strategy,’ hereinafter referred to as ‘The Report,’ is more of a vision than of a strategy. The present article addresses three observations made on The Report; namely, dose response, PBPK modeling, and in vitro testing. An additional observation this author has of the document is that a role for a scientist who can analyze the big picture is missing from the document. Science today is necessarily composed of specialists in many areas because science today encompasses many diverse, specific fields. Each specialist is in a world of his or her own and unable to integrate all the facts. Must we wait for another Newton or Einstein?

Acute and chronic dose/response effect of benzene inhalation on the peripheral blood, bone marrow, and spleen cells of CD-1 male mice

1981 ◽  
Vol 59 (2) ◽  
pp. 204-214 ◽  
Author(s):  
James D. Green ◽  
Carroll A. Snyder ◽  
Joseph LoBue ◽  
Bernard D. Goldstein ◽  
Roy E. Albert
Keyword(s):  
Bone Marrow ◽  
Dose Response ◽  
Peripheral Blood ◽  
Male Mice ◽  
Spleen Cells ◽  
Response Effect ◽  
Chronic Dose ◽  
Dose Response Effect

Using Benthic Assessment Techniques To Determine Combined Sewer Overflow and Stormwater Impacts in the Aquatic Ecosystem

2000 ◽  
Vol 35 (3) ◽  
pp. 365-398 ◽  
Author(s):  
Q. Rochfort ◽  
L. Grapentine ◽  
J. Marsalek ◽  
B. Brownlee ◽  
T. Reynoldson ◽  
...  
Keyword(s):  
Biological Effects ◽  
Sediment Toxicity ◽  
Benthic Communities ◽  
Toxicity Testing ◽  
Benthic Invertebrate ◽  
Complete Characterization ◽  
Sediment Chemistry ◽  
Combined Sewer Overflows ◽  
Sources Of Pollution ◽  
Combined Sewer

Abstract Urban wet-weather sources of pollution such as Stormwater and combined sewer overflows (CSOs) can contribute significantly to the contamination of receiving waters, particularly in sediment depositional areas near outfalls. Analyses of sediment chemistry alone are not sufficient to fully assess the effects of these discharges. Toxicity testing and evaluations of benthic invertebrate communities, in conjunction with chemical analyses, provide a more complete characterization. This study assessed relationships among three separate aspects of the benthic environment:sediment chemistry (metals, PAHs and nutrients) and particle size, sediment toxicity (ten endpoints with four benthic taxa), and benthic invertebrate community structure. In this initial survey, ten sites in five different study areas, representing a range of receiving water environments exposed to Stormwater and CSO discharges, were sampled in October 1998. Results of analyses indicated that while contaminant (metals and PAHs) concentrations were relatively high in sediments, biological effects were not evident Toxicity of sediments was low and altered benthic communities were not detected. Neither toxicity endpoints nor benthic community descriptors were related to sediment contaminant levels. To improve the power of these assessments, future investigations of Stormwater and CSO discharge impacts should use “upstream/downstream” sampling designs and study sites with minimal variability of habitat conditions.

Presenting Toxicology to the Public: The Middle School

1994 ◽  
Vol 13 (4) ◽  
pp. 314-320
Author(s):  
Michael J. Derelanko
Keyword(s):  
Middle School ◽  
Middle School Students ◽  
Dose Response ◽  
Toxicity Testing ◽  
Animal Research ◽  
School Students ◽  
The Public ◽  
Basic Concepts

Toxicologists are being called upon to educate the public about the value of toxicity testing and the important role animals play in this regard. This article discusses the importance of toxicologists educating students in the middle school about the science of toxicology and suggests various ways to convey basic concepts of toxicity, dose response, and animal research to students in these grades. The methods described in this article have been developed and used successfully by the author in making presentations to middle school students.

scholarly journals Nonmonotonic Dose–Response Curves Occur in Dose Ranges That Are Relevant to Regulatory Decision-Making

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581879828 ◽  
Author(s):  
Corinne E. Hill ◽  
J. P. Myers ◽  
Laura N. Vandenberg
Keyword(s):  
Dose Response ◽  
Endocrine Disrupting Chemicals ◽  
Toxicity Testing ◽  
Adverse Outcomes ◽  
High Dose ◽  
Human Populations ◽  
Response Curves ◽  
Regulatory Decision ◽  
Adverse Effect Level ◽  
Dose Response Curves

Non-monotonic dose response curves (NMDRCs) occur in cells, tissues, animals and human populations in response to nutrients, vitamins, pharmacological compounds, hormones and endocrine disrupting chemicals (EDCs). Yet, regulatory agencies have argued that NMDRCs are not common, are not found for adverse outcomes, and are not relevant for regulation of EDCs. Under the linear dose response model, high dose testing is used to extrapolate to lower doses that are anticipated to be ‘safe’ for human exposures. NMDRCs that occur below the toxicological no-observed-adverse-effect level (NOAEL) would falsify a fundamental assumption, that high dose hazards can be used to predict low dose safety. In this commentary, we provide examples of NMDRCs and discuss how their presence in different portions of the dose response curve might affect regulatory decisions. We provide evidence that NMDRCs do occur below the NOAEL dose, and even below the ‘safe’ reference dose, for chemicals such as resveratrol, permethrin, chlorothalonil, and phthalates such as DEHP. We also briefly discuss the recent CLARITY-BPA study, which reported mammary adenocarcinomas only in rats exposed to the lowest BPA dose. We conclude our commentary with suggestions for how NMDRCs should be acknowledged and utilized to improve regulatory toxicity testing and in the calculation of reference doses that are public health protective.

scholarly journals The Development of a Probabilistic Dose–Response for a Burn Injury Model

2017 ◽  
Vol 182 (S1) ◽  
pp. 202-209
Author(s):  
Anthony Iyoho ◽  
Laurel Ng ◽  
Philemon Chan
Keyword(s):  
Dose Response ◽  
Burn Injury ◽  
Injury Model
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