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Children and the unborn child

3. Exposure

In order to estimate the risks which chemical substances may pose to the unborn child, infants and children, it is necessary to know the possible exposure routes and exposure patterns for different types of substances in the various age groups. The exposure route and pattern varies between the different age groups. Thus, exposure of the unborn child and the young infant is dependent on the exposure of the pregnant/lactating woman, whereas exposure of infants and children is also influenced by differences in nutritional/energy requirements, activity level, and the location where activities are taking place. The natural curiosity of infants and children may significantly increase their exposure to a wide variety of chemical substances.

An additional aspect in relation to the time at which exposure occurs is that exposure to environmental xenobiotics prenatally or during childhood may result in functional defects or predisposition to development of certain diseases which may affect the individual during the whole life span.

In the following, several types of exposure will be addressed:

There is nearly always possibility for simultaneous exposure via several routes. For example, substances such as lead, mercury, and persistent organic pollutants may be present in foodstuffs, drinking water, and ambient air and thus result in simultaneous exposure via oral ingestion, inhalation, and dermal contact.

Exposure may occur to different types of chemical substances for instance:

	persistent organic pollutants
	pesticides
	metals
	food additives
	pharmaceuticals
	vapours/fumes
	combustion products/particulate matter
	plasticizers
	alcohol
	environmental tobacco smoke
	cosmetics
	household chemicals

3.1 Exposure of the unborn child

Most substances entering the bloodstream of the pregnant mother will be distributed to the embryo/foetus (see section 2). The exposure of the unborn child will thus be a reflection of the exposure pattern of the mother: her dietary habits and lifestyle, whether she drinks alcohol, smokes, is under medical treatment, or is subjected to occupational exposure. Persistent substances accumulated in the body of the mother (from previous exposures) may be redistributed, thus leading to exposure of the unborn child. An example is lead deposited in the bones of the mother, which is distributed to the foetus during gestation.

The embryo-foetal exposure to chemical substances depends on the amount the mother is, and has been (if the substance is accumulated in the body), exposed to and on the extent to which the substance passes the placenta. Organic mercury and lead compounds pass the placenta and reach the unborn child, while cadmium to some extent will be withheld in the placenta. During embryogenesis, the placental transfer of weakly acidic substances is favoured, while during late gestation, pH of the foetal compartment changes and favours the transfer of weakly alkaline substances (see section 2).

Regarding medical treatment of pregnant women, benefits and risks of the intended treatment should be carefully evaluated for the mother and the unborn child before the treatment is actually given.

The infant may be exposed to chemical substances through breastfeeding, because many substances, especially lipophilic ones, which the lactating mother is exposed to or has been exposed to at an earlier point in her life, are secreted into the breast milk. Some substances may even concentrate in breast milk.

Breast milk has a lipid content of 3 to 4%. The intake of breast milk of infants (4-6 weeks of age) has been quantified to an average intake of about 750 g/day (EPA 1997; Butte et al. 1984)

PCB and dioxins are examples of substances, which are liberated from the fat tissue of lactating mothers and secreted into the breast milk. In Denmark, an investigation has been performed to determine the content of dioxins and PCB in the breast milk of Danish mothers. The average concentration of dioxins + PCB was 30 pg TEQ/g fat (TEQ = 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents) corresponding to an average daily intake of the sucking child of 150 pg TEQ/kg b.w./day. A TDI of 1-4 pg TEQ/kg b.w./day (dioxins and dioxin-like PCBs) has been set (WHO 1999) as an average daily intake for the whole lifetime. (SST/FDIR 1999).

Data from recent Danish and Swedish studies show reductions in the concentrations of organochlorine compounds such as PCBs and DDT in human milk throughout the last decade. In contrast hereto, the concentration of organobromine compounds such as polybrominated diphenyl ethers (PBDEs) has increased continuously with levels showing an exponential increase from 1972 and a doubling time of 5 years. (SST/FDIR 1999, Norén & Meironyté 1998).

The mean intake of infant formula is slightly higher than for breast milk. A Swedish study showed that the mean breast milk intake at the age of 6 weeks is 746 g/day compared to an intake of cow’s milk formula of 823 g/day and an intake of soy formula of 792 g/day (Köhler et al. 1984 - quoted from EPA 1997).

Infant formulas are based on cow’s milk or on soy products and may be contaminated as described in section 3.2.4. Infant formulas can be divided into those "ready to feed" and those consisting of dry powder to be mixed with water immediately before use. Water is the major ingredient in infant formula. The water used for industrial manufacturing of "ready to feed" formulas is purified e.g. by active carbon filtration (NRC 1993) and is not anticipated to contain any chemical substances of concern. The water used for infant formula in households is most likely tap water and may contain chemical substances which may result in an unacceptable exposure of the infant (see section 3.2.3).

Drinking water may contain high concentrations of naturally occurring substances such as fluoride, copper, and nitrate as well as contaminants such as persistent organic pollutants and pesticides. Therefore, drinking water may constitute a health risk for all population groups; however, infants and young children are at the highest risk, since they, on a bodyweight basis, may consume up to 5 times more water than adults (Lawrie 1998). Intake values for regulatory purposes are given in Table 3.3.

Generally, it is very difficult to estimate the intake of chemical substances from drinking water, because the concentrations and types of substances vary from one geographical site to another and also depend on whether ground water or surface water is the source of drinking water.

Fluoride is one example of a natural constituent in drinking water. A concentration of about 1 mg/l of fluoride in drinking water may give rise to discoloration of the tooth enamel and adverse skeletal changes may be observed at concentrations around 3 to 6 mg/l. Fluoride also provides a protective effect against dental carries, especially in children; this protective effect increases with concentrations of fluoride in drinking water up to about 2 mg/l.

Nitrate is another example of a natural constituent in drinking water and drinking water obtained from certain wells may contain high levels of nitrate either due to direct contamination or as a result of bacterial contamination. When the concentration of nitrate exceeds 50 mg/l (the limit value in Denmark), drinking water will be the major source of total nitrate intake, especially for bottle-fed infants. High nitrate levels pose a particular health risk to infants. Infants have a higher pH in the stomach which favours the reduction of nitrate to nitrite. Nitrite is involved in the oxidation of normal haemoglobin to methaemoglobin, which is unable to transport oxygen to the tissues. Haemoglobin is more easily oxidised in infants compared to older children and adults and the enzymatic system for reduction of methaemoglobin is not fully developed in infants.

Other contaminants in the drinking water may present due to the release from the water pipes and installations. Copper is one example where infants may have an increased risk of experiencing toxic effects. The concentration of copper in the body is held relatively constant by homeostatic mechanisms; however, children under one year of age are probably more susceptible than adults to copper toxicity because the homeostatic mechanisms may not have fully developed.

Infants and young children have a dietary pattern different from that of adults. They have a higher food intake per kg bodyweight and they also have other food preferences and needs. In the Nordic dietary recommendations (Nordic Council of Ministers 1996) it is stated that the percentage of energy from fat in the diet of infants younger than 6 months should be minimum 40%, for children from 1 to 3 years 30 to 35%, and for adults less than 30% of the total energy intake.

Comprehensive British surveys (between 1986 and 1993) have shown that, on a body weight basis, the nutritional requirements (energy, protein, and water) of infants and young children are 2-5 times higher than for adults; the largest difference is seen for water intake.
The average consumption by young children (aged 1½ to 4½) of the main food categories (fruit, vegetables, bread, cereals, meat, fish, eggs) was 1.7 to 2.7 times higher, on a body weight basis, than that by adults.
Dairy products (including cheese and yoghurt but excluding milk), puddings, sugar and confectionery were found to be of particular significant importance in the diet of the young child, with an intake up to 5 times the equivalent adult figure (after correction for body weight). For beverages, the difference between young children and adults were even more marked; excluding milk, young children obtained over 80% of their fluid intake from soft drinks (75% was squashes and 25% was carbonated drinks) giving an average level of consumption which was 16 times the equivalent adult figure. (Lawrie 1998)

A Danish survey (National Food Agency 1996) showed that, relative to their bodyweight, children drink up to nine times as much milk as adults, and that they eat more cereals (including bread and porridge), fruit, vegetables, products of animal origin and sweets than adults, see Table 3.1.

Table 3.1
Mean intake of food commodities in Denmark 95¹

¹Estimated from "Danskernes kostvaner 95" (National Food Agency 1996) including unpublished data.
²Dry weight
³Tap water consumed directly from the tap. Tap water used for cooking and dilution of e.g. soft drink concentrates is not included.

Cow’s milk

Cow’s milk is a traditional constituent of the childhood diet and young children (1 to 3 years) on the average consume approximately nine times as much as adults (35-44 years). The predominant exposure to chemical substances through cow’s milk and milk products are in form of residues from veterinary medicinal products and from substances present in the feed of the dairy cow.

Products of animal orgin

Younger children eat relatively more meat, fish and poultry than adults. Meat and poultry may be contaminated with chemical substances, which pass from the soil, possibly through the feed, to the animals. In fish, particularly in fat fish, lipid-soluble persistent substances (e.g., methylmercury, dioxins, PCBs, and chlorinated pesticides) typically accumulate through the food chain.

Cereals

Cereals may contain pesticide residues and chemical substances from soil. The pesticide residues from herbicides, fungicides, insecticides, and growth regulators used on cereals are normally concentrated in the bran, which is often removed during processing. Organo-phosphates and pyrethroids form the major part of residues after post-harvest treatments.
Certain metals tend to concentrate in special crops, e.g., cadmium is found in high concentrations in sunflower seeds, which are used in large amounts in some types of bread. Cadmium is also found in other cereals. In a Swedish study (Eklund & Oskarsson 1999), the highest intake, 0.44 µg Cd/ kg b.w. per day on a body weight basis, was found in 6-month-old children, consuming the recommended amount of wheat-, oat- and milk-based formulas; this intake is below the PTWI (Provisionally Tolerable Weekly Intake) of 7 µg/kg b.w. (1 µg/kg b.w. per day, for comparison only) (WHO 1989).

Fruit

Fruit is a food commodity, which may contain pesticide residues because a large part of the production is treated with pesticides during growth. The pesticide residues will often be reduced through washing, cooking, or by removal of the peel. Thus the highest exposure occurs when children eat unwashed whole fresh fruit.

Vegetables

In general, young children eat more vegetables relative to their bodyweight than adults and data from the Danish survey (National Food Agency 1996) indicate that children eat a higher quantity of vegetables harvested from the soil (potatoes and carrots) than harvested above the soil (leafy vegetables). Higher levels of pesticide residues are found on vegetables harvested above the soil than from the soil because they are treated directly.
All vegetables may contain chemical substances present in the soil and some substances may even accumulate in the vegetables. Examples of chemical substances, which have been detected in vegetables, are metals, chlorinated solvents, pesticides and polyaromatic hydrocarbons.

Soft drinks and fruit juice

According to both a Danish (National Food Agency 1996) and a British (Lawrie 1998) survey, children between 1 and 3 years in average consume, relative to their body weight, more than ten times the amount of soft drinks and fruit juice compared to adults. The relatively higher consumption of soft drinks and fruit juices means that children are exposed to relatively higher amounts of the food additives used in these drinks such as artificial sweeteners and colouring agents. Some soft drinks are diluted in the home and this also means a relatively higher intake of tap water. Tap water used for this purpose is not included in the figure for tap water in Table 3.1.

Sugar

Children have a higher intake of sugar compared to adults. This is not considered to lead to higher exposure to chemical substances because sugar is refined to a degree where almost no contaminants are found.

Essential elements

In cases of essential elements such as copper and fluoride, the relationship between intake and risk has a U-shaped curve, with risks from deficiency associated with low intakes and risk of toxicity associated with high intakes. The range of optimal intakes to meet the biological requirement as well as to prevent risk of toxicity are for some substances rather narrow.

Children and infants are by nature curious and continuously examine their environment. One way in which they investigate their surroundings is by putting objects into their mouth. During outdoor playing activities, children get into contact with soil both by dermal contact and by ingestion.

A consequence of children’s oral examination of their environment is the risk of intoxication which in some cases is fatal. In Denmark, around 800 to 1300 children are every year (the number has decreased during the last years) referred to hospitals due to accidental intoxications; however, only very few cases are fatal (3-4 per year). Acute intoxications are primarily due to unintentional exposure to household chemicals, organic solvents, drugs, irritating gases, asphyxiants in fumes, and poisonous animals, plants and fungi. The most frequently reported intoxication among young children during the nineties is ingestion of liquid paraffins (lamp oil); however, the number of these cases has been reduced during the last few years probably because of general information to consumers and because of exclusion of attractive colours and fragrances in lamp oils. (Ishøy & Jensen 1999).
General prophylactic measures include the introduction of child resistant closures to several products, including household chemicals and organic solvents.

Exposure to chemical substances may also occur through oral contact with toys and other products used by children such as soothers, teats, glue, finger paint, or cosmetics made for children. Soothers may lead to exposure to chemical substances due to migration of substances from the different materials used (plastic, silicone, or natural rubber); one example is migration of mercapto benzothiazole (MBT) from natural rubber.
Toys may contain a number of chemical substances such as plasticisers (e.g. phthalates), metals, and organic solvents, which may migrate from the toy to the saliva when the child is sucking or chewing on the material.

Soil ingestion is related to the hand-to-mouth activity and is most profound in the age range from 1 to 3 years. Several factors may influence the intake of soil. The major factor is the access to free soil surfaces, others include the climate, which affects the time being spent outdoors, and whether the ground is frozen or covered with snow. There is an uneven distribution of soil ingestion as many children eat small amounts while a few eat large amounts (Larsen 1998). Average figures for soil and dust ingestion are reported to be in the range of 39 to 271 mg/day (Osimitz 1999). A study with Dutch children aged 2 to 4 years showed a mean value of 105 mg/day (range 23 to 362 mg/day) compared to a value for hospitalised children of 49 mg/day (Clausing et al. 1987). For occasional single exposure, a figure of 10 g/day is given for children deliberately eating large amounts of soil (EPA 1997). Intake values for soil ingestion for regulatory purposes are given in Table 3.4.

Children at rest inhale a relatively larger volume of air compared to adults. A further increased inhalation volume is due to a higher activity level during play. In Table 3.2, estimates of daily inhalation volumes (based on oxygen consumption associated with energy expenditures) are shown for different age groups. Inhalation volumes used for regulatory purposes are given in Table 3.6.

Table 3.2
Daily inhalation rates calculated from food-energy intakes (Layton 1993 - quoted from EPA 1997).

Children are exposed to indoor air pollutants e.g., from exposure to tobacco smoke, wood burning, cooking, vapours from household and hobby products, vapours emitted from furniture and building materials, and housedust to which many chemical substances are adsorbed.

Due to a greater amount of time spent outdoor and relatively higher inhalation volume compared with adults, children are exposed to a higher degree to ambient air pollutants such as particulate matter, PAHs, nitrogen dioxide, and ozone (Larsen et al. 1997). In busy roads, children inhale air from a level near the ground which make them more exposed to vehicle exhaust from the traffic.

For whole body exposures, children and infants have higher exposures than adults because of their greater surface to bodyweight ratio.
Many of the substances in the environment of infants and children, which pose a problem in relation to non-dietary ingestion, may also pose a problem when getting in contact with the skin e.g., household chemicals, childcare products, and products for personal hygiene.
Clothes to which there is an extended and close contact, may contain chemical substances. For nappies, in addition to a long contact time, there is also an occlusive effect.

Cosmetics are widely used, may be applied several times a day, and may be used on large skin areas. For infants and young children, the exposure to cosmetics is related to their parent behaviour. As the child grows older, it will gradually take over the use of cosmetics for personal hygiene and other products intended for application to the skin such as face paint. If the product is applied on damaged skin, there will be a greater absorption of the constituents. Likewise, when a product is applied on the skin and covered with a nappy, a higher absorption will occur because of the occlusive effect.

More and more products are marketed directly for children, some of which may contain chemicals getting in contact with the skin e.g., face paint, child cosmetics, wet tissues, and plasticine.

Children are subjected to a relatively higher exposure to chemical substances compared to adults because of physiological differences, differences in dietary needs or food preferences, or different activity patterns. The following aspect should be emphasized:

The unborn child shares the exposure pattern of the mother. Most substances to which the mother is exposed will be passed on to the unborn child. Substances accumulated in the mother’s tissues may be redistributed and passed on to the unborn child.

The breastfed child shares the exposure pattern of the mother. Substances accumulated in the fatty tissue of the mother will be passed on to the child through the breast milk.

Drinking water may be contaminated with chemical substances or contains naturally occurring substances at levels which may pose a risk to infants and young children since they, on a bodyweight basis, may consume up to 5 times more water than adults.

Nutritional requirements (energy, protein, and water) of infants and young children are 2-5 times higher than for adults.

Relative to their bodyweight, children drink up to nine times as much milk as adults. They eat more of the main food categories (fruit, vege-tables, bread, cereals, meat, fish, eggs) and sweets than adults.

Children consume large amounts of soft drinks containing artificial sweeteners and colouring agents.

Soil ingestion is most profound in the age range from 1 to 3 years. Small children may in single occasions deliberately eat as much as 10 gram of soil.

Children inhale a relatively larger volume of air compared to adults and may therefore to a higher degree be exposed to indoor and ambient air pollutants.

More and more products aimed directly at children are put on the market, some of which may contain chemical substances getting in contact with the skin e.g., face paint, child cosmetics, wet tissues, and plasticine.

Because of their curiosity and behavioural pattern, children may more easily be involved in emergencies due to oral, inhalational, or dermal exposure to household chemicals or other chemical products containing dangerous substances.

When estimations of exposure of infants and children are made, special attention should be directed towards the fact that infants and children have a different activity pattern from adults. Child specific activities include hand to mouth activity, different food preferences, and their curiosity-driven examinations of their surroundings.

Tables 3.3 to 3.6 give an overview of volumes of intake used by different authorities and organisations in derivations of guidance values for drinking water (Table 3.3), soil (Table 3.4 for oral ingestion; Table 3.5 for dermal contact), and ambient air (Table 3.6):

Table 3.3
Values used for drinking water intake

Table 3.4
Values used for soil ingestion