- ‘blanket’ approach
- adverse effects
- ambient air pollutants
- Atopic dermatitis
- chemical contaminants
- chemical insults
- chemical toxicity
- chemotherapeutic agents
- childhood cancer
- diagnostic criteria
- Early exposure
- environmental factors
- Exposure assessment
- exposure to antigens
- exposure to chemicals
- food additives
- gene expression
- Genetic factors
- geographic heterogeneity
- Hygiene hypothesis
- neurodevelopmental disorders
- no observed adverse effect level
- otitis media
- patterns of exposure
- pharmacokinetic characteristics
- reproductive effects
- respiratory diseases
- skin barrier function
- Sperm quality
- volatile organic chemicals
- windows of vulnerability
TR 096 : Trends in Children’s Health and the Role of Chemicals | July 2005
Children, compared to adults, can be more sensitive, less sensitive, or equally sensitive to changes in health status as a consequence of exposure to chemicals. Broadly based statements indicating that children are generally more sensitive to chemical insults are not supported by existing scientific data.
The susceptibility of children is related to the specific physical, toxicological, and age-related pharmacokinetic characteristics of the particular chemical as well as the stage of a child’s development. The likelihood of a specific health outcome following exposure of children is also related to the patterns of exposure that reflect both the presence of chemicals in the environment as well as behavioural characteristics of the developing child. The overall effect of these variations in both susceptibility and exposure is to create specific time frames during which vulnerability to adverse effects is elevated; so called ‘windows of vulnerability’.
Trends in Children’s Health
In comparing time trends of disease, a number of factors must be taken into account. These include: improved reporting systems; changes in diagnostic criteria/procedures; a more active approach to early detection of cases to improve prognosis and a better health care system in general. There is clear evidence of increasing rates of asthma in children, although rates in some countries may now have stabilised. There is no convincing evidence of widespread trends in other acute or chronic childhood respiratory diseases. Indoor air quality appears to be related to both asthma and, in some cases, to other respiratory-related diseases (such as otitis media). Interpretation of the available information on asthma and allergies is made difficult by inconsistent application of diagnostic criteria over place and time. Contemporaneous with the increasing frequency of asthma, data also suggest that other atopic disorders such as upper respiratory tract and food allergy may be increasing. Atopic dermatitis remains the most common skin disorder in young children.
Although the frequency of neurodevelopmental disorders such as autism and attention deficit/hyperactivity disorder (ADHD) is commonly believed by the public to be increasing, the limited data available do not support this perception. Besides, diagnostic criteria have changed significantly over time.
Data on reproductive effects are also limited and often suffer from serious data quality issues. Whilst geographic heterogeneity is apparent, broad population trends for these outcomes (e.g. sperm quality, hypospadias, cryptorchidism) are difficult to identify. However, there is clear evidence for decreasing puberty age in females.
There is no evidence for major trends in the frequency of childhood cancer. Data indicate that developed countries tend to have a gradually increasing incidence of leukaemia with a corresponding drop in the incidence of lymphoma. Increases in brain tumour frequency are possibly related to the development of new diagnostic capabilities rather than to a true change in the incidence in the rate of malignant disease. With the increasing number of childhood cancer survivors, secondary cancers following chemotherapy appear to be on the increase.
Role of Environmental Exposure, including Chemicals
A wide range of environmental factors is thought to have an impact on children’s health, extending well beyond industrial chemicals. These factors include nutrition (protein, vitamins, antioxidants), lifestyle and behaviour choices such as tobacco and alcohol use, parental health, socio-economic status, choice of living environment (urban vs. rural, etc.), and parent-sibling behaviour. From the available data, no general conclusions on the contribution of specific chemicals can be drawn across the multiple health outcomes addressed in this report.
There is a need to distinguish between factors causing asthma from those acutely exacerbating an existing state of the disease. It remains difficult to make this distinction in practice, as some non-allergenic chemical agents may modulate the ability of other materials to cause asthma. Overall, genetic propensity and exposure to antigens (mainly proteins) remain the most important determinants of childhood atopic disease.
Primary chemical contributors to exacerbation of childhood asthma appear to be ambient air pollutants (particulates, NOx, SOx, ozone, etc.) and lifestyle-related indoor air pollutants such as environmental tobacco smoke. Some evidence suggests that volatile organic chemicals can play a role in the exacerbation of childhood asthma, primarily as a result of airway irritant effects. Primary allergens responsible for asthma, and respiratory food allergies, are almost invariably proteins, not environmental industrial chemicals. Nickel is probably the most common allergen for chronic skin sensitisation in the general public.
Early exposure not only to allergens but also to infectious diseases, immunisations, and other environmental immune stimuli appears to reduce the frequency of asthma and atopic diseases (‘hygiene hypothesis’). Conversely, lack of environmental exposure to these factors seems to increase the risk of allergic disease. No widespread trend attributable to industrial chemicals is apparent.
Exposure to lead, mercury, and polychlorinated biphenyls (PCBs) is associated with neurodevelopmental disorders. However, the relationship of neurobehavioural changes to these chemicals at general environmental levels has not been well established, except for lead. Neurodevelopmental disorders in the general population are probably largely the result of genetic, socio-economic, and lifestyle choices (particularly smoking) as well as important gene-environment interactions, for example parents and siblings with ADHD have a profound effect on the child’s environment.
The risk for cryptorchidism and hypospadias appears to be related to a variety of non-environmental factors. While it is established that high-level hormonal stimuli can affect reproductive tissues and processes, the actual contribution of lower-level exposure to endocrine agents to reproductive alterations in intact, homeostatic organisms is unclear. The one clearly identified trend in reproductive health in the developed world, the earlier onset of puberty in girls, is probably due to lifestyle changes leading to improved health and nutrition. Sperm quality varies widely over time and place, with no clearly established global trend. Many genetic and lifestyle factors may affect sperm quality from pre-natal to adult life.
Genetic factors are important in childhood cancer. There is no evidence that environmental chemicals other than chemotherapeutic agents used in the treatment of initial malignancies play any significant role in the aetiology of child cancers. A number of factors related to pregnancy and lifestyle (e.g. parental smoking, birth weight, gestational illness such as pre-eclampsia) have been associated with alterations in the frequency of adult cancers as a result of childhood exposure.
Assessing Risks to Children
The regulatory requirements for safety testing vary between different classes of chemicals. Data from a core set of toxicological studies are not available for all chemicals. It is increasingly recognised that a ‘blanket’ approach to toxicological testing is not required. A tiered and integrated approach involving use patterns and exposure potential, degree of concern from existing hazard information, together with the use of predictive tools (e.g. QSARs and read-across between chemical categories) are likely to provide adequate hazard data for a risk assessment.
Risk assessment methodology currently in use incorporates significant uncertainty factors, usually based on a No-Observed-Adverse-Effect Level (NOAEL) in animals, to account for potential interspecies and intraspecies differences in susceptibility to chemical toxicity. Additional uncertainty factors can be added for data insufficiency (i.e. lack of a NOAEL). Analyses suggest that the existing uncertainty factors are likely to be adequately protective for children. Future risk assessments will benefit from on-going research into exposures specific to children.
There are a number of scientific developments that could increase the accuracy of assessing risks to children. Large mother-child and child-youth cohort studies are emerging, but will not yield significant information for many years. Limitations in statistical power for rare disease outcomes mean that studies must be large (with cost and logistic consequences) to make a meaningful contribution. Further, with studies testing multiple hypotheses, findings will need to be externally validated via mechanistic or specifically targeted additional epidemiological research.
The future role of genomics and proteomics as biomarkers for exposure or adverse outcome in assessing risks to children’s health is unclear but such techniques could allow for a more rigorous toxicity evaluation as well as provide biological information on the lifestage-specific consequences of environmental exposures. The use of biomarkers for both exposure and disease outcomes offers challenges, especially if incorporated into cohort studies. Biomarkers of either exposure or effect suffer from various limitations, but may offer significant advantages when they improve accuracy of exposure estimation and/or diagnosis of disease.