Summary of Dose-Response Modeling for Developmental Toxicity Studies

Hunt, Daniel L.; Rai, Shesh N.; Chin-Shang Li
October 2008
Dose-Response;2008, Vol. 6 Issue 4, p352
Academic Journal
Developmental toxicity studies are an important area in the field of toxicology. Endpoints measured on fetuses include weight and indicators of death and malformation. Binary indicator measures are typically summed over the litter and a discrete distribution is assumed to model the number of adversely affected fetuses. Additionally, there is noticeable variation in the litter responses within dose groups that should be taken into account when modeling. Finally, the dose-response pattern in these studies exhibits a threshold effect. The threshold dose-response model is the default model for non-carcinogenic risk assessment, according to the USEPA, and is encouraged by the agency for the use in the risk assessment process. Two statistical models are proposed to estimate dose-response pattern of data from the developmental toxicity study: the threshold model and the spline model. The models were applied to two data sets. The advantages and disadvantages of these models, potential other models, and future research possibilities will be summarized.


Related Articles

  • NTP Draft Brief on DEHP. Barrett, Julia R. // Environmental Health Perspectives;Oct2006, Vol. 114 Issue 10, pA580 

    The article provides information on the draft brief released by the National Toxicology Program (NTP) in May 2006 about di(2-ethylhexyl) phthalate (DEHP) exposure and toxicity in the U.S. The NTP brief summarizes the report of experts of the NTP Center for the Evaluation of Risks to Human...

  • A Signal-to-Noise Crossover Dose as the Point of Departure for Health Risk Assessment. Sand, Salomon; Portier, Christopher J.; Krewski, Daniel // Environmental Health Perspectives;Dec2011, Vol. 119 Issue 12, p1766 

    BACKGROUND: The U.S. National Toxicology Program (NTP) cancer bioassay database provides an opportunity to compare both existing and new approaches to determining points of departure (PoDs) for establishing reference doses (RfDs). OBJECTIVES: The aims of this study were a) to investigate the...

  • Human cell line toxicity of binary and ternary chemical mixtures in comparison to individual toxic effects of their components Winder, C.; Markovic, B.; Malich, G. // Archives of Environmental Contamination & Toxicology;Oct1998, Vol. 35 Issue 3, p370 

    Contaminated site projects involve health risk assessment proceduresthat must consider potential interactive effects of present contaminants. In order to establish a quick and reliable method that accountsfor smaller than additive, additive, or greater than additive toxic effects, this study...

  • Investigations into the concept of a threshold for topoisomerase inhibitor-induced clastogenicity. A. Lynch; J. Harvey; M. Aylott; E. Nicholas; M. Burman; A. Siddiqui; S. Walker; R. Rees // Mutagenesis;Jul2003, Vol. 18 Issue 4, p345 

    Although the application of the concept of a threshold to risk assessment is widespread, there remains little experimental evidence for the existence of thresholds for genotoxic compounds, other than aneugens. The clastogenicity of topoisomerase inhibitors is believed to result from the...

  • Dose-rate effects of ethylene oxide exposure on developmental toxicity. Weller, E.; Long, N.; Smith, A.; Williams, P.; Ravi, S.; Gill, J.; Henessey, R.; Skornik, W.; Brain, J.; Kimmel, C. Kimmel G.; Holmes, L.; Ryan, L. // Toxicological Sciences;Aug1999, Vol. 50 Issue 2, p259 

    In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges...

  • Heavy Metal Toxicity -- An Unsuspected Illness. Bowring, Janine // Positive Health;Aug2005, Issue 114, p28 

    Focuses on the concerns over the heavy metal toxicity and unknown root cause of a number of serious health issues. Problem with the presence of heavy metals in the body and their ability to bio-accumulate; Occurrence of heavy metal exposure; Symptoms of heavy metal toxicity.

  • Carcinogenicity Evaluation: Comparison of Tumor Data from Dual Control Groups in the CD-1 Mouse. Baldrick, Paul; Reeve, Lesley // Toxicologic Pathology;2007, Vol. 35 Issue 4, p562 

    Current regulatory thinking allows for the use of single control groups for rodent carcinogenicity testing although there has been a trend until recently to use dual control groups. To date, virtually nothing has been published on whether a shift from dual to single control groups will affect...

  • Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Oberd√∂rster, G√ľnter; Maynard, Andrew; Donaldson, Ken; Castranova, Vincent; Fitzpatrick, Julie; Ausman, Kevin; Carter, Janet; Karn, Barbara; Kreyling, Wolfgang; Lai, David; Olin, Stephen; Monteiro-Riviere, Nancy; Warheit, David; Hong Yang // Particle & Fibre Toxicology;2005, Vol. 2, p8 

    The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences...

  • It's Not Only Rocket Science. Rak, Andrew // Environmental Forum;May/Jun2010, Vol. 27 Issue 3, p38 

    The article discusses the debate on the possible health effects of human exposure to low levels of perchlorate. It mentions that the chemical is said to be first discovered to have entered the environment from rocket fuel and munitions and can be found in fertilizers, bleaches, fireworks and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics