Developmental Immunotoxicity (DIT): The Why, When, and How of DIT Testing

A workshop entitled ‘Developmental Immunotoxicology and Risk Assessment’ was held on 12–13 June 2001, in Washington, DC. The workshop was organized jointly by the Immunotoxicology Technical Committee (ITC) of the International Life Sciences Institute's (ILSI) Health and Environmental Sciences Institute (HESI) with input from the U.S. Environmental Protection Agency (EPA). Growing public concern that early exposure of the developing immune system to immunotoxic compounds may cause significant or persistent postnatal immunosuppression prompted the workshop. The main goal of the workshop was to examine scientific questions that underlie developmental immunotoxicity tests and the interpretation of the results as they relate to human risk assessment. A second goal was to provide a framework, based on current scientific knowledge, for the development of meaningful testing guidelines. The workshop focused on a series of questions that included how to address critical windows of exposure, how to develop and apply more predictive endpoints, does early chemical exposure cause transient or permanent effects on the immune system, as well as other related questions. On the first day, experts were invited to give scientific presentations relating to comparative developmental immunology, models of immunosuppression, and the regulatory aspects of developmental immunotoxicology. The second day was devoted to a panel discussion that included all the speakers as well as meeting participants, which attempted to answer each of the specific questions raised at the workshop. In general, it was acknowledged that there are a variety of techniques available for assessing immunosuppression in adult animal models, but there is uncertainty about how to apply these to a developing animal, especially if the goal is to have some standard procedure that can be applied for regulatory risk assessment. It was pointed out that although we know a lot about the developing immune system of individual species, we do not know how to relate the significance of drug or chemical effects on these systems in terms of human hazard. Overall, the panel deemed the area of developmental immunotoxicity to be still in its infancy and outlined strategies that could lead to the development of standard practices.

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Prospects for Developmental Immunotoxicity Guidance and an Update on ICH S8

Journal of Immunotoxicology ◽

10.1080/15476910500387173 ◽

2005 ◽

Vol 2 (4) ◽

pp. 217-220 ◽

Cited By ~ 2

Author(s):

Kenneth L. Hastings

Keyword(s):

Developmental Immunotoxicity

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Developmental Immunotoxicity of Atrazine in Rodents

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/j.1742-7843.2007.00175.x ◽

2008 ◽

Vol 102 (2) ◽

pp. 139-145 ◽

Cited By ~ 40

Author(s):

Alexander M. Rowe ◽

Kathleen M. Brundage ◽

John B. Barnett

Keyword(s):

Developmental Immunotoxicity

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Developmental immunotoxicity testing for hazard identification.

10.26481/dis.20121115it ◽

2012 ◽

Author(s):

I. Tonk

Keyword(s):

Hazard Identification ◽

Developmental Immunotoxicity

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What’s So Special about the Developing Immune System?

International Journal of Toxicology ◽

10.1080/10915810801978110 ◽

2008 ◽

Vol 27 (2) ◽

pp. 223-254 ◽

Cited By ~ 72

Author(s):

Leigh Ann Burns-Naas ◽

Kenneth L. Hastings ◽

Gregory S. Ladics ◽

Susan L. Makris ◽

George A. Parker ◽

...

Keyword(s):

Immune System ◽

Toxicity Testing ◽

Life Stages ◽

Significant Progress ◽

Immune Development ◽

Immune Parameters ◽

Current State ◽

State Of The Science ◽

Developmental Immunotoxicity ◽

Nonhuman Species

The evolution of the subdiscipline of developmental immunotoxicology (DIT) as it exists today has been shaped by significant regulatory pressures as well as key scientific advances. This review considers the role played by legislation to protect children’s health, and on the emergence of immunotoxcity and developmental immunotoxicity guidelines, as well as providing some context to the need for special attention on DIT by considering the evidence that the developing immune system may have unique susceptibilities when compared to the adult immune system. Understanding the full extent of this potential has been complicated by a paucity of data detailing the development of the immune system during critical life stages as well as by the complexities of comparisons across species. Notably, there are differences between humans and nonhuman species used in toxicity testing that include specific differences relative to the timing of the development of the immune system as well as more general anatomic differences, and these differences must be factored into the interpretation of DIT studies. Likewise, understanding how the timing of the immune development impacts on various immune parameters is critical to the design of DIT studies, parameters most extensively characterized to date in young adult animals. Other factors important to DIT, which are considered in this review, are the recognition that effects other than suppression (e.g., allergy and autoimmunity) are important; the need to improve our understanding of how to assess the potential for DIT in humans; and the role that pathology has played in DIT studies in test animals. The latter point receives special emphasis in this review because pathology evaluations have been a major component of standard nonclinical toxicology studies, and could serve an important role in studies to evaluate DIT. This possibility is very consistent with recommendations to incorporate a DIT evaluation into standard developmental and reproductive toxicology (DART) protocols. The overall objective of this review is to provide a ‘snapshot’ of the current state-of-the-science of DIT. Despite significant progress, DIT is still evolving and it is our hope that this review will advance the science.

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