Children’s health issues span a wide range of topics, including diseases such as asthma and childhood cancer, conditions such as low birth weight, congenital anomalies and neurodevelopmental defects such as autism and ADHD, as well as effects on the endocrine, reproductive and immune systems. Events leading to the majority of childhood deaths in the first year of life include birth defects and low birth weight. Threats to children’s health include air pollution (indoor and outdoor), infections, and contaminants in drinking water and food supplies, while developing/underserved areas may also face poor sanitation, vector born diseases, and malnutrition.
One of the most-studied substances affecting children’s health is lead. Exposure to lead can cause a wide variety of effects depending on the level of exposure, including reduced IQ and attention deficits. While the effects of lead are well-known, other substances that have been associated with potential alterations in children’s health include methylmercury, phthalates, PCBs/PBBs, ethanol, tobacco, pesticides and several pharmaceuticals, including thalidomide, Accutane, the angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, and others. An understanding of dose-response relationships and mode of action is important for providing a strong scientific basis to characterize the weight of evidence for potential effects of human exposures to chemicals or pharmaceuticals.
Exponent scientists have extensive experience in children’s health issues, reproductive and developmental toxicology, developmental neurotoxicology, quantitative risk assessment and pediatric drug development. Our experience spans the chemical and pharmaceutical industry, academia and government, with efforts on projects at the state, national, and international level. We have practical experience in planning, conducting and coordinating investigative human studies and regulatory guideline-based toxicity studies. This includes interpreting study data relative to children’s health and risk assessment for standard-setting and safety assessment.
Our team of scientists has extensive regulatory experience as senior scientists/directors at the EPA and UK Pesticides Safety Directorate, as members of Science Advisory Panels for the FDA, and national and international expert committees. We have been involved in developing U.S. and international regulatory guidelines for neurotoxicity, reproductive and developmental toxicity testing and risk assessment, screening assays for endocrine disruptors, cancer risk assessment as it relates to children, and quantitative benchmark dose risk assessment. In addition, we have experience in conducting and interpreting gene-environment interaction studies of environmental exposures and genetic susceptibility in human fetuses and infants. We have been involved in developing guidelines for conduct of pregnancy registries for drugs and also for advising on the recent guidelines for pregnancy and lactation labeling, which will have a major impact on the type of information provided to patients and health care providers on drug use during pregnancy and lactation.
Using an integrated approach, our staff advises clients on issues such as testing registration, data literature analysis potential children’s health issues, product stewardship, litigation. Studies necessary for any given regulatory authority may have implications in other parts the world (e.g., classification labeling restrictions; acute reference dose; FQPA factors). Exponent’s international team scientists offers an array of services, from interpretation advice directing programs and risk management proposals, to help navigate these issues.
Framework for Children’s Risk Assessment
Over the last 10-15 years, there has been growing interest in applying risk assessment methods specifically to children. This concern motivated EPA to develop the Voluntary Children’s Chemical Evaluation Program (VCCEP), which asks chemical manufactures to develop risk assessments specific to children for commonly used chemicals. For some widely used chemicals, this represented a daunting challenge. Exponent scientists, Dr. Richard Reiss and Dr. Elizabeth Anderson, developed a framework for conducting children’s risk assessments under VCCEP (see schematic below).
The VCCEP is unique in its risk-based, tiered approach, and because it focuses on children and requires a comprehensive consideration of all reasonably foreseeable exposure pathways for a particular chemical.
The framework provides guidance for interpreting multiple sources of exposure information and developing a plausible list of exposure pathways for a chemical. It also discusses the larger ratios of food intake to body weight and inhalation rate to body weight in children that can result in higher dosages to children for a given chemical concentration, compared to adults.
>Finally, the framework provides guidance for utilizing a tiered-approach for efficiently conducting an assessment by first using simple, screening-level approaches and then, if necessary, using more complex, refined exposure assessment methods. A generic example is presented to demonstrate the framework.
The framework was published in the peer-reviewed journal Risk Analysis in 2003.