| Front page | | Contents | | Previous | | Next |

Children and the unborn child

6. Regulations

Chemical substances are present around us and consequently we are all exposed to a number of such substances e.g., via the environment, food and beverages, cosmetics, and through a number of different products which many of us use daily. Additionally, adults and young people may be exposed to chemical substances via the working environment and children by contact with toys and childcare products (see section 3).

In order to assure the best possible protection against adverse effects resulting from exposure to chemical substances, several regulations within the different areas have been issued. This part of the report briefly summarises the most relevant Danish regulations on chemical substances with focus on the protection of children and pregnant women, including their unborn child, exposed to chemical substances.

It should be noticed that the regulations of chemical substances are based on the existing knowledge with regard to adverse health effects and risks related to the use of the substances. It must be emphasised, that for the great majority of substances used, very little - if any - knowledge exists regarding the relevant exposure scenarios and/or vulnerability of children, including the unborn child.

6.1 Environmental contamination

In Denmark, health based limit values (quality criteria) are set for chemical substances in soil, drinking water and ambient air according to the principles laid down in the Guideline for health based evaluation of chemical substances in drinking water (MST 1992a) and in Appendix A of the Industrial Air Pollution Control Guidelines (MST 1992b). The principles as they are used today will briefly be outlined here:

When the available toxicological data have been evaluated, the hazard considered most important, "the critical effect", for setting the quality criteria for a given substance is identified. Generally, the effects are considered to be of more concern the lower the concentration or dose at which they occur, and the effect observed at the lowest concentration or dose level often forms the basis for the calculation of a tolerable concentration or tolerable daily intake (TDI).
In doing this, a "no observed adverse effect level" (NOAEL) or when this is not possible a "lowest observed adverse effect level" (LOAEL) is identified. Having identified a NOAEL (or a LOAEL), three safety factors (uncertainty factors) SF_I, SF_II, and SF_III are used for the calculation of the tolerable concentration or TDI. SF_I accounts for interspecies variation in susceptibility and SF_III accounts for the quality and relevance of the data. SF_II accounts for differences in intraspecies susceptibility, i.e. this safety factor is used for the protection of groups in the population that may be more susceptible than the general population such as children, pregnant women and their unborn child, elderly or sick people; in general a default value of 10 is used for SF_II.

Following calculation of the tolerable concentration or TDI, the health based limit values are derived for the relevant media by division of the value for the tolerable concentration or TDI by a given standard exposure level of the relevant media. For derivation of the limit value for drinking water and ambient air, a daily standard exposure for an adult person is used. Thus, no specific attention is normally given to exposure of children. For soil exposure, however, the standard exposure used for calculation of the limit value is a standard exposure for soil exposure of children (values for daily soil ingestion or soil in contact with skin), as exposure to soil is considered especially important (and critical) for children. To ensure that the total daily intake for various media does not exceed the tolerable concentration or TDI, a certain percentage (often 10%) of the tolerable daily exposure level can be assigned to the relevant media and in this way account for other important exposure routes such as exposure through the food.

6.2 Chemical substances and products

Classification and labelling

Within the EU, regulations on classification and labelling of chemical substances are based on total harmonised directives (EEC 1967, with amendments). In Denmark, the Statutory Order on classification, packaging, labelling, sale and storage of chemical substances and preparations (MEM 1997) implements the relevant EU Council Directives into national legislation. The Statutory Order provides the regulations for evaluating the inherent properties of a chemical substance or preparation in relation to hazard identification and assessment.
The hazard identification and assessment cover a number of important toxicological endpoints such as acute toxicity, irritative and corrosive properties, sensibilisation, repeated dose toxicity, reproductive and developmental effects, and genotoxic and carcinogenic properties. Chemical substances considered dangerous according to the regulations are classified and labelled with symbols and indications of danger, nature of special risks (R-phrases) and safety advises (S-phrases).

Classification is normally based on results from specific animal experiments according to EU guidelines (Annex V to EEC 1967, with amendments). In most of these studies, no specific attention is paid to whether specific age groups could be identified as sensitive subgroups.

A number of R- and S-phrases are, however, specifically related to protection of children and/or pregnant women:

Chemical substances which are classified as reproductive toxicants in category 1 (substances known to impair fertility or to cause developmental toxicity in humans) and category 2 (substances which should be regarded as if they impair fertility or cause developmental toxicity in humans) are labelled with R60 "may impair fertility" or R61 "may cause harm to the unborn child", respectively.

Chemical substances which are classified as reproductive toxicants in category 3 (substances which cause concern for human fertility or for humans owing to possible developmental toxic effects) are labelled with R62 "possible risk of impaired fertility" or R63 "possible risk of harm to the unborn child", respectively.

Chemical substances which are known or suspected to be secreted into the breast milk at toxic levels are labelled R64 "may cause harm to breastfed babies".

The S-phrase S2 "keep out of the reach of children" is assigned to every classified chemical substance or preparation.

Packaging, sale and storage

The Statutory Order on classification, packaging, labelling, sale and storage of chemical substances and preparations (MEM 1997) also include regulations which ensure that children will not come into contact with most of the dangerous chemicals.
Chemical substances and preparations which are classified as carcinogenic, mutagenic, or reproductive or developmental toxicants in category 1 and 2 must not be sold to the general public.
Chemical substances and preparations which are classified as "very toxic" (Tx) and "toxic" (T) can only be sold to individuals of the general public who have a special permission from the police.
Chemical substances and preparations must not be marketed in containers which are considered to attract children’s attention. For certain classified chemical substances and preparations, special closures (child-resistant fastenings) should be used for the containers and such products should be stored out of the reach of children.

Risk assessment in EU and OECD

Within the EU and OECD, specific programs on risk assessment for chemical substances are on-going. In the EU, a directive (EEC 1993a) provides the regulation on risk assessment of new notified chemical substances and two Council regulations (EEC 1993b, EEC 1994a) on risk assessment of existing substances. Denmark takes part in the risk assessment programs according to the EU regulation, but no specific regulation have been issued in Denmark to implement this regulation.
The risk assessment process, in relation to both human health and the environment, entails a sequence of actions: effect assessment (hazard identification and dose (concentration) - response (effects) assessment), exposure assessment (estimation of the concentrations/doses to which human populations or environmenal compartments are or may be exposed) and risk characterisation (estimation of the incidence and severity of the adverse effects likely to occur in a human population or environmental compartment due to actual or predicted exposure to a substance). The risk characterisation is carried out separately for three subgroups of the population: workers, consumers, and man exposed indirectly via the environment; only the last two subgroups include children. In the risk characterisation for consumers and man exposed indirectly via the environment, the interspecies variation (see 6.1) is taken into account when considering the margin of safety (the ratio between the NOAEL or LOAEL and the estimated exposure).
For some specific substances (e.g., phthalates), children have been considered as a specific subgroup of consumers as children may be exposed to these substances in a way which is not considered relevant for adults.

No specific EU or OECD guidelines for risk assessment for children and pregnant women and their unborn child have been issued.

Assessment based on available data

Classification and risk assessment are based on available data. In general, the available data on a specific chemical substance seldom allow for an evaluation with respect to whether children or the unborn child should be considered more susceptible than adults. Concerning fertility and teratogenicity, data exist only for 20-30 % of the 2500 high production volume chemicals, and for thousands of chemicals produced in smaller quantities this percentage is expected to be considerably lower (Danish Board of Technology 1996).

Testing of chemical substances new chemical substances

For new notified chemical substances (substances which were not on the market within the EU at any time in the 10 years prior to 18 September 1981), step-wise, tonnage related data requirements have been issued. The number of tests required is dependant on the supply level. The results of one study should generally be evaluated before another study is initiated.

base-set testing

Base-set testing is demanded for a new substance produced or imported in amounts of 1-10 tonnes/year per producer or importer in an EU member state. No specific tests to detect adverse effects on reproduction are required. However, it is indicated that there is a requirement at this level to "screen" new substances for their potential to cause reproductive toxicity.

level 1 testing

Level 1 testing is additional to the base-set testing and includes a fertility study (one species, one generation, males and females, most appropriate route of administration) and a teratogenicity study (one species, most appropriate route of administration). Level 1 testing may be required when supply levels reach 10 tonnes/year per producer or importer (or 50 tonnes/year cumulative per producer or importer in the EU) and shall be required at supply levels of 100 tonnes/year (500 tonnes cumulative) unless the notifier can give good reason why a particular test is not appropriate or an alternative scientific study would be preferable.

level 2 testing

Level 2 testing is required for high production volume chemicals, i.e. when supply levels reach 1000 tonnes/year (5000 tonnes cumulative) and includes fertility study (three-generation study; only if an effect on fertility has been established at Level 1), developmental toxicity study on peri- and post-natal effects, and teratogenicity study (species not employed in the respective Level 1 study).

less than 1 tonne/year

For new substances produced in amounts less than 1 tonne/year, no tests on reproductive toxicity are required.

existing chemical substances

For existing high production volume chemical substances (substances which were on the market within the EU at any time in the 10 years prior to 18 September 1981 and produced in amounts above 1000 tonnes/year), the data to be made available shall at least include the base-set required for new substances. Any gaps in the base-set data should be filled, unless the producers or importers can justify not providing it.

6.3 Cosmetics

The use of cosmetics by different age groups, including infants and children, has increased during the last years. Consequently, exposure to chemical substances via cosmetics is increasing and it has been suggested that this is a contributing factor for the increased incidence of allergy observed among the general population. Illustrative examples of the increasing use for infants and children include bath and shower preparations, suncare products, wet tissues, hair care products (including colours and bleaches), and special cosmetics intended for children.

Within the EU, regulations on cosmetics are based on totally harmonised directives (EEC 1976a, with amendments). In Denmark, the Statutory Order on cosmetic products (MEM 1998a) implements the relevant EU Council Directives into national legislation. The regulation on exposure to chemical substances in cosmetic products is built up of different lists:

Annex 1 lists the different cosmetic products which are regulated.

Annex 2 lists the chemical substances which are not allowed intentionally as ingredients in cosmetic products.

Annex 3 lists the chemical substances to be used in cosmetic products according to specific limitations.

Annex 4-6 are positive lists for pigments, preservatives and UV-filters, respectively.

In order to protect children against exposure to specific chemical substances in cosmetics, a few specific substances have been banned from cosmetic products intended for children below 3 or 12 years of age.

The evaluations of chemical substances to be used in cosmetic products are discussed in the EU Scientific Committee on Cosmetics. In the Committee’s evaluation of a specific substance, the safety margin for expected daily use is estimated; however, no specific considerations are taken regarding the use of the substance in products which will be used for children.

6.4 Toys and childcare products

Within the EU, regulations on toys are based on total harmonised directives. The Statutory Order on safety regarding toys and products which can be mistaken for foodstuffs (FST 1995) implements the EU Council Directives (EEC 1987, EEC 1988a, with amendments) into national legislation. According to these regulations, toys may generally not contain dangerous chemical substances (those substances which are classified according to the EU Council Directive (EEC 1967) on classification, packaging and labelling of chemical substances and preparations) in such amounts, which will give rise to development of adverse effects in children. Furthermore, specific migration limits have been set for 8 metals (antimony, arsenic, barium, cadmium, chromium, lead, mercury, selenium). It should be noted, however, that a safe migration limit for a substance in a specific toy only can be set on the basis of a realistic worst-case exposure scenario with respect to toy exposure. The scenarios may differ considerably for different kind of toys and the possibility for exposure during use (and misuse).
Denmark has prohibited the use of phthalates in toys and childcare products for children of the age of 0 to 3 years (MEM 1999).
EU has adopted measures prohibiting the placing on the market of toys and childcare articles intended to be placed in the mouth by children under three years of age made of soft PVC containing one or more of 6 specific phthalates (DINP, DEHP, DBP, DIDP, DNOP, BBP) (EU 1999).

Several other national regulations have been issued in order to protect children from exposure to chemicals through their use of toys.

6.5 Food additives, pesticides and contaminants in food

6.5.1 Food additives

In Denmark, food additives are regulated by the Statutory Order on food additives (FM 1997) which implements the relevant EU Council Directives (EEC 1978, EEC 1988b, with amendments) into national legislation. The use and use levels of permitted food additives are given in "Positivlisten" (VFD 1997). The establishment of the use levels is based on the ADI (acceptable daily intake) which is estimated from the "no observed adverse effect level" (NOAEL) considered from evaluations of studies on experimental animals or, in cases where a NOAEL cannot be identified, the "lowest observed adverse effect level" (LOAEL), by applying a safety factor of normally 100. This safety factor is considered to take into account the intraspecies variation, i.e. to take into account that the observed effects may vary in severity within the population, thereby protecting children and pregnant women against possible adverse health effects from exposure to the substance.

The ADI is not considered to cover the use of food additives in infant formula, since the usual toxicity test regimen does not cover this situation; therefore, specific evaluations are carried out for the use of food additives in infant formulas.

Budget method

Having obtained the ADI, the use levels are derived by applying the so-called ‘Budget method’. The Budget method, which has been developed by the National Food Agency, now the Danish Veterinary and Food Administration, is based on considerations of the total daily intake of energy (calories) and liquid. The intake of liquid per kg body weight varies with age, being highest in small children, thereafter declining rapidly during childhood and more slowly in adult age. The Budget method uses the recommended liquid intake at the age of two, 100 ml/kg b.w., as the basis for the calculations of maximum intakes. Intake of food (energy) per kg body weight is also dependent on age. The Budget method uses the energy requirement of 100 kcal for a one-two year old child as a basis for the limit of food intake which will sufficiently protect adults also. (Larsen 1992).

6.5.2 Pesticides

Sale and use

Before sale and use, the active substance in the formulated pesticide product has to be authorised in the EU, whereas the formulation itself has to be authorised in the actual Member State for each crop. The active substances are evaluated according to the EU regulations (EEC 1967, with amendments) on classification, packaging and labelling of chemical substances and preparations, see 6.2. In Denmark, the formulations are evaluated according to the Statutory Order on pesticides (MEM 1998b) which implements the relevant EU Council Directives (EEC 1991, EEC 1976, with amendments) into national legislation.
The evaluation of the formulations are based on risk assessment for specific uses and therefore generally only apply to adult workers. Although children and pregnant women may also be exposed to formulated pesticides, e.g. following their use in gardens and indoor such uses are generally not included in the evaluation of the formulations.

To protect the general population, the most toxic formulations which are labelled as "very toxic" or "toxic" according to the EU regulations on classification, packaging and labelling of chemical substances and preparations (see 6.2), are not allowed for use in gardens, public areas, kindergartens etc. This includes substances which are classified as reproductive or developmental toxicants in category 1 and 2. Formulations are banned in Denmark when the substance is carcinogenic or mutagenic in category 1 and 2. Also when exposure is greater than the AOEL (Acceptable Operator Exposure Level), use of the product cannot be approved. The AOEL is based on the no effect level (NOAEL) from animals studies with a safety factor of at least 100. Formulated products classified as "irritant" with the R-phrase R41 "risk of serious damage to eyes" are not allowed in Denmark.

A separate risk evaluation is not done for re-entry in private homes after professional application of products not allowed for private use. However, in green-houses, where relevant, this evaluation is done for re-entry exposure.

Specific considerations related to protection of children and/or pregnant women are taken into account in the evaluation of a given formulation. Data from studies on reproductive and developmental effects as well as effects in sucking pups of the active substance(s) are requested for the authorisation.
Furthermore, when estimating the ADI for the active substance one of the safety factors, often set to 10, takes into account the intraspecies variation, i.e. that the observed effects may vary in severity within the population.

MRLs in foodstuffs

EU establishes harmonised maximum residue levels (MRLs) for pesticides in foodstuffs, which are in force in all Member States. In Denmark, the Statutory Order on maximum residue levels for pesticides in foodstuffs (FM 1999a) implements the relevant EU Council Directives (EEC 1976b, EEC 1986a,b, with amendments) into national legislation; the MRLs for a number of substances are given in the Annexes of the Statutory Order. The establishment of MRLs is based on the principles of Good Agricultural Practice (GAP¹) and the estimated food consumption per person. From the MRL the TMDI (theoretical maximum daily intake) is calculated and compared with the ADI estimated according to the same practice as already mentioned for food additives, see 6.5.1. If the TMDI exceeds the ADI, more refined methods are used to calculate a more realistic intake using e.g. the actual median residue levels determined after GAP supervised trials, and reduction factors from the processing of food. If the ADI is still exceeded, then the proposed MRLs cannot be endorsed.
For pesticides with a highly acute toxicity, acute reference doses are also estimated and compared with the MRL to protect against such effects.

The Danish Veterinary and Food Administration has analysed the residue levels of pesticides in many different foodstuffs. The estimated intake of the most frequently detected pesticides indicates that the average intake for adults is maximally a few percent of the ADI; therefore, it may be considered that most children also are protected against possible adverse health effects from exposure to the actual pesticides in foodstuffs.

In the EU, a general limit value of 0.01 mg/kg of residues of individual pesticides in processed baby foods and infant formulae has been issued (EEC 1999a,b). This limit value is considered to provide a very high degree of protection of children against adverse health effects from exposure to pesticides. Furthermore, specific pesticides (listed in Annexes to the Directives) must not be used in agricultural products intended for the production of baby foods and infant formulae. These regulations will be implemented in a revision of the Statutory Order on pesticides.

6.5.3 Veterinary medicinal products

EU establishes harmonised maximum residue levels (MRLs) for veterinary medicinal products in milk and foods of animal origin, which are in force in all Member States (EEC 1990, with amendments); the MRLs for a number of substances are given in the Annexes to the Council Regulation (EEC 1990, with amendments).

MRLs for veterinary medicinal products are established on the basis of the ADI assuming that a person weighing 60 kg consumes a certain amount of meat and fish and 1.5 l of milk (cheese and butter included) ("standard food package"). By using this "standard food package" in relation to children, the milk intake is underestimated as children often drink more than 1.5 l of milk (see section 3); however, the intake of meat and/or fish will often be overestimated as children generally consume less of these foods than adults. Thus, the ADI is generally not exceeded for children under normal circumstances. However, if an MRL is only set for milk (e.g. products for intramammary administration) and the ADI is solely allocated to this commodity; the underestimation of the milk intake for children may consequently result in exceeding the ADI even if the level of the given residue in milk is within the MRL.

6.5.4 Contaminants

Chemical substances arising from different sources may occur in foodstuffs. In Denmark, the Statutory Order on certain contaminants in foodstuffs (FM 1999b) implements the relevant EU Council Directives (EEC 1993c, EEC 1997, with amendments) into national legislation; limit values for some metals (lead, cadmium, mercury and tin), nitrate, and mycotoxins (aflatoxin and ochratoxin A) are given in the Annexes. The evaluation of contaminants in foodstuffs are carried out according to the same practice as already mentioned for food additives, see 6.5.1. However, a TDI (tolerable daily intake) instead of an ADI is estimated to signal that the contaminants are not added to foodstuffs deliberately. Furthermore, the database for evaluation of contaminants is less comprehensive than for food additives and pesticides and therefore, higher safety factors are often applied when the TDI is estimated.

Since 1983, the Danish Veterinary and Food Administration has analysed the levels of a number of contaminants in relevant foodstuffs. The levels of the analysed contaminants have significantly decreased during recent years and no specific dietary advice to pregnant women are considered necessary.

6.6 Working environment

In Denmark, the general regulations for employers and workers are given in the Danish Working Environment Act (1998) which include specific regulations regarding young people; these regulations are further specified in the Statutory Order on young people’s employment (AM 1996). Specific regulations are also given for pregnant women in the Statutory Order on the performance of the work (AM 1994). These regulations have been issued to protect young people and pregnant women against exposure to chemical substances and preparations via their working environment.

Young people

The specific regulations for young people below the age of 18 is given by the Statutory Order on young people’s employment (AM 1996); the Statutory Order goes beyond the relevant EU Council Directive (EEC 1994b).
Generally young people below the age of 18 are not allowed to work with or in other ways be exposed to specific chemical substances and materials listed in Annex 2a to the Statutory Order. Most of the listed chemical substances are covered by the EU regulations (EEC 1967, with amendments) on classification, packaging and labelling of chemical substances and preparations (see 6.2) and the following are included:

	substances classified as "very toxic" (Tx), "toxic" (T), "corrosive" (C), "explosive" (E)
	substances with the R-phrases R12, R39, R45, R46, R60, R61
	substances classified as "harmful" (Xn) and at least one of the following R-phrases R40, R42, R48, R62, R63
	substances labelled as "irritant" (Xi) and R43
	substances and materials included on the Danish Working Environment Service’s list of chemicals and processes considered as carcinogenic as well as materials containing more than 0.5% of the chemicals
	organic solvents included on the Danish Working Environment Service’s list of organic solvents as well as materials containing more than 0.5% solvents.

Pregnant women

The specific regulations for pregnant women are given by the Statutory Order on the performance of the work (AM 1994); the Statutory Order implements certain regulations in the relevant EU Council Directives (EEC 1989, EEC 1992, with amendments). Other regulations are implemented by collective agreements or other legislation.

Generally, a specific evaluation of the pregnant woman’s working environment, including the influence of exposure to chemical substances, is requested to identify possible influence on the pregnancy. If this evaluation identify any influences, a more detailed evaluation is requested regarding the nature, extent and duration of the influence(s) to identify any risks for the pregnant woman and the unborn child. If any risk is identified, the working environment of the pregnant woman should be improved or, in cases where such an improvement is not possible, the pregnant woman should be removed from the actual working environment.

Annex 4 to the Statutory Order lists the chemical substances which must at least be considered when evaluating the risk during pregnancy and lactation. Included are:

	chemical substances and materials classified and labelled with R40, R45, R46, R60, R61, R62, R63, and R64
	chemical substances and materials included in the Danish Working Environment Service’s Statutory Order no 300, 1993 regarding carcinogens
	chemical substances and materials included in the Danish Working Environment Service’s Statutory Order no 52, 1988 regarding materials containing volatile chemicals, including solvents
	pesticides
	volatile anaesthetics
	mercury
	lead
	cytostatics
	carbon monoxide
	chemical substances, which pose a proven risk by dermal uptake.

6.7 Drugs

6.7.1 Registration of drugs

In EU, there is at present no mandatory requirement for pharmaceutical companies to investigate new medicinal products in children.
The pharmaceutical industry is however encouraged to investigate the safety and efficacy of a product in children, if it is likely to be of therapeutic benefit to this age group (CPMP 1997). In case sufficient documentation is provided, the license may cover treatment of children.

6.7.2 Principles for dosing children, and pregnant and lactating women

The unborn child as well as infants are considered potentially more susceptible to adverse effects of drugs than adults. The principles for medical treatment of children and pregnant and lactating women are outlined below. The principles and recommendations are described in the catalogue of registered pharmaceuticals in Denmark, Lægemiddelkataloget (1997).

Children
According to Lægemiddelkataloget (1997), schematic dosing of infants and children is difficult and is generally practised as mg drug per kg body weight.

Because of the differences between children and adults in response to drugs, simple proportionate correction in the adult dose for body weight may not be adequate to determine a safe and effective dose for children, especially for the very young. Dosage requirements, cardiac output, hepatic and renal blood flow, and glomerular filtration rate in children and in adolescents of widely differing sizes have been found to correlate better with body surface area than body weight. According to this concept, a child’s dose can be calculated from the formula:

where 1.8 m² is the surface area of an average 70-kg adult. The surface area of a child can be determined from its body weight using the observation that surface area is proportional to body weight to the 0.7 power. (Rowland & Tozer 1995).

Another approach for determining the dose for children is to test the drug in this age group and the Committee for Proprietary Medicinal Products (CPMP) has issued a Note for Guidance on Clinical Investigation of Medicinal Products in Children (CPMP 1997).

Drug therapy in new-borns and particularly premature babies requires special attention because of the very rapid changes in renal and hepatic function in these early stages of life. Therefore, dosing of this age group is generally referred to paediatric specialists.

Pregnant women

Most chemical substances, including drugs, taken by pregnant women can cross the placenta and enter the tissues of the developing embryo and foetus with consequent risk of teratogenic effects in the form of malformations or other developmental effects (see section 2 and 3 for further details).
Relatively few chemical substances and drugs are known human teratogens; however, a potential for inducing teratogenic effects by the remainder cannot be fully excluded as the mechanisms by which teratogenic effects can be induced are poorly understood and are probably multifactorial. Therefore, every drug should be considered as a potential human teratogen and medical treatment of pregnant women and women who plan pregnancy should be avoided if possible. However, some women with chronic diseases are dependent on medical treatment. Regarding medical treatment of pregnant women with chronic diseases, benefits and risks of the treatment should be carefully evaluated for the mother and the unborn child and in case of medical treatment, these women have to be very carefully monitored during their pregnancy.
(Lægemiddelkataloget 1997).

As a general practise, medical treatment during pregnancy should be based on the following principles (Lægemiddelkataloget 1997):

	Avoid new drugs because preclinical studies do not fully exclude a risk to the human foetus.
	Avoid medical treatment during the first trimester where the risk for malformations are greatest.
	Manage medical treatment by monitoring the plasma concentration.
	Avoid combination of drugs.

Lactating women

Most drugs administered to lactating women can be detected in the breast milk (see section 2 and 3 for further details). The concentration of drugs in the breast milk is highly variable and is dependent on many different factors; however, the knowledge within this area is still very limited. Therefore, as a general practise, medical treatment of lactating women should be avoided. If medical treatment cannot be avoided, the sucking child should be very carefully followed. (Lægemiddelkataloget 1997).

6.8 The Precautionary principle

The precautionary principle is a principle that opens up for regulatory action on the basis of suspicions for harmful consequences rather than waiting for cases or a full scientific evidence. In the context of this report, the use of the precautionary principle may be relevant for the aim of protecting defined vulnerable groups in the population against potential hazardous exposures for which the harmful consequences are not fully understood.

The first actual mentioning of the precautionary principle in connection with legislation was in German legislation in 1976, where it is called the Vorsorgeprinzip: "Environmental policy is not fully accomplished by warning off imminent hazards and the elimination of damage which occurred. Precautionary environmental policy requires furthermore that natural resources are protected and demands on them are made with care." Since then, and in various wording, the precautionary principle has been incorporated in a series of international treaties (e.g., the EU Amsterdam Treaty from 1998) and declarations. In many of these the principle has been connected mainly to hazardous chemical substances, but there are also examples of broader approaches to environmental issues as such. (MST 1998).

In Danish legislation the precautionary principle is not explicitly mentioned, but it is often reflected in the introductory comments to various environmental acts, the central ones being the Environmental Protection Act, the Chemical Substance and Product Act, the Marine Environment Act, and the Gene Technology Act. (MST 1998).

Both in Denmark and abroad, there has been increasing focus on the precautionary principle in recent years. In line with the increasing complexity of environmental issues, politicians, enterprises, and authorities are expected to allow this doubt to benefit the environment and through this public health. However, it is not clear either in Denmark nor in other countries, what the principle specifically involves and how it should be applied in the day-to-day work. To have a debate on the issue and to give a better understanding of the principle, the Danish EPA held a conference on 29 May 1998 which was attended by industry people, researchers, green organisations, politicians, authorities, and other interested parties. The conference provided no clear answers and no easy solutions. However, in general there was broad agreement among the presenters and during the debates that the precautionary principle must be regarded as a political norm for both legislation and administration. It was expressed in the discussion that there was a great need for more guidance on how to apply the precautionary principle in practice. (Danish EPA 1998).

Recently, the Commission of the European Communities has published a communication on the precautionary principle (EU 2000).

6.9 Overall

As mentioned in section 1, the Danish Government initiated a cross-ministerial overview concerning the administrative measures for protecting children and pregnant women. From this overview, which also covered the chemical areas described in this section, it was concluded that in specific areas increased effort should be made to increase the protection of children and pregnant women and several future initiatives in different ministerial sectors were proposed.

With respect to environmental factors and chemical regulations, it was concluded that more specific focus on protection of children and/ or pregnant women should be put in regulatory procedures in relation to: the use of chemicals in cosmetics and toys; risk assessment procedures in the EU; risk assessment procedures in relation to the national derivation of limit values for air, soil and water; and the procedures for approval of pesticides (especially pesticides for domestic use) and for risk assessment of food additives and food contaminants.

6.10 References

AM (1998). The Danish Working Environment Act, Statutory Order from the Ministry of Labour no 497 of 29 June, 1998. In Danish.

AM (1996). The Statutory Order from the Ministry of Labour no 516 of June 14, 1996, on young people’s employment. In Danish.

AM (1994). The Statutory Order from the Ministry of Labour no 867 of 13 October, 1994, on the performance of the work. In Danish.

CPMP (1997). Note for Guidance on Clinical Investigation of Medicinal Products in Children. The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit, CPMP/EWP/462/95.

Danish EPA (1998). The precautionary principle. Extracts and summary from the Danish Environmental Protection Agency’s conference on the precautionary principle, Eigtveds Pakhus, Copenhagen, 29 May 1998.

EEC (1999a). Commission directive 1999/39/EC of 6 May 1999 amending Directive 96/5/EC on processed cereal-based foods and baby foods for infants and young children.

EEC (1999b). Commission directive 1999/50/EC of 25 May 1999 amending Directive 91/321/EC on infant formulae and follow-on-formulae.

EEC (1997). Commission Regulation (EC) No 194/97 of 31 January 1997 setting maximum levels for certain contaminants in foodstuffs.

EEC (1994a). Commission Regulation (EC) No 1488/94 of 28 June 1994 on risk assessment for existing substances.

EEC 1994b). Council Directive 94/33/EC of 22 June 1994 on the protection of young people at work.

EEC (1993a). Commission Directive 93/67/EEC of 20 July 1993, laying down the principles for the assessment of risks to man and the environment of substances notified in accordance with Council Directive 67/548/67.

EEC (1993b). Council Regulation 793/93/EEC of 23 March 1993 on the evaluation and control of the risks of existing substances.

EEC (1993c). Council Regulation (EEC) No 315/93 of 8 February 1993 laying down Community procedures for contaminants in food.

EEC (1992). Council Directive 92/85/EEC of 19 October 1992 on the introduction of measures to encourage improvements in the safety and health at work of pregnant workers and workers who have recently given birth or are breastfeeding.

EEC (1991). Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market.

EEC (1990). Council Regulation (EEC) No 2377/90 of 26 June 1990 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin.

EEC (1989). Council Directive 89/391/EEC of 12 June 1989 on the introduction of measures to encourage improvements in the safety and health of workers at work.

EEC (1988a). Council Directive 88/378/EEC of 3 May 1988 on the approximation of the laws of the Member States concerning the safety of toys.

EEC (1988b). Council Directive 89/107/EEC of 21 December 1988 on the approximation of the laws of the Member States concerning food additives authorised for use in foodstuffs intended for human consumption.

EEC (1987). Council Directive 87/357/EEC of 25 June 1987 on the approximation of the laws of the Member States concerning products which, appearing to be other than they are, endanger the health or safety of consumers.

EEC (1986a). Council Directive 86/362/EEC of 24 July 1986 on the fixing of maximum levels for pesticide residues in and on cereals.

EEC (1986b). Council Directive 86/363/EEC of 24 July 1986 on the fixing of maximum levels for pesticide residues in and on foodstuffs of animal origin.

EEC (1978). Council Directive 79/112/EEC of 18 December 1978 on the approximation of the laws of the Member States relating to the labelling, presentation and advertising of foodstuffs for sale to the ultimate consumer.

EEC (1976a). Council Directive 76/768/EEC of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic products.

EEC (1976b). Council Directive 76/895/EEC of 23 November 1976 relating to the fixing of maximum levels for pesticide residues in and on fruit and vegetables.

EEC (1967). Council Directive 67/548/EEC of 27 June 1967 on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.

EU (2000). Communication from the Commission on the precautionary principle. Commission of the European Communities, Brussels, 2.2.2000 COM(2000) 1 final.

EU (1999). Commission Decision of 7 December 1999 adopting measures prohibiting the placing on the market of toys and childcare articles intended to be placed in the mouth by children under three years of age made of soft PVC containing one or more of the substances di-iso-nonyl phthalate (DINP), di(2-ethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), di-iso-decyl phthalate (DIDP), di-n-octyl phthalate (DNOP), and butylbenzyl phthalate (BBP). 1999/815/EC.

FM (1999a). The Statutory Order from the Ministry of Food, Agriculture and Fisheries no 465 of June 15, 1999, on maximum residue levels for pesticides in foodstuffs. In Danish.

FM (1999b). The Statutory Order from the Ministry of Food, Agriculture and Fisheries no 57 of January 22, 1999, on certain contaminants in foodstuffs. In Danish.

FM (1997). The Statutory Order from the Ministry of Food, Agriculture and Fisheries no 942 of December 11, 1997, on food additives. In Danish.

FST (1995). The Statutory Order from the National Consumer Agency of Denmark no 329 of May 23, 1995, on safety regarding toys and products which can be mistaken for foodstuffs. In Danish.

Larsen JC (1992). Food additives, Positive list. Philosophy, regulation, special conditions. In: Risk Management and Risk Assessment in Different Sectors in Denmark, Proceedings from the ATV Conference "Risk Management, Hazard and Risk Assessment in Connection with the Setting of Limit Values for Chemicals" June 1992, ATV Danish Academy of Technical Sciences, 109-124.

Lægemiddelkataloget (1997). Dosing of drugs to children, 38-40; drugs and pregnancy, 45-46; secretion of drugs into breast milk, 46. In Danish.

MEM (1999). The Statutory Order from the Ministry of Environment and Energy no 151 of March 15, 1999, on prohibiting the use of phthalates in toys to children at the age of 0 to 3 years and in certain childcare products etc. In Danish.

MEM (1998a). The Statutory Order from the Ministry of Environment and Energy no 303 of May 18, 1998, on cosmetic preparations. In Danish.

MEM (1998b). The Statutory Order from the Ministry of Environment and Energy no 241 of April 27, 1998, on pesticides. In Danish.

MEM (1997). The Statutory Order from the Ministry of Environment and Energy no 801 of October 23, 1997, on classification, packaging, labelling, sale and storage of chemical substances and preparations. In Danish.

MST (1998). The precautionary principle. Extracts and summary from the Danish Environmental Protection Agency’s conference on the precautionary principle, Eigtveds Pakhus, Copenhagen, 29 May 1998.

MST (1992a). Health based evaluation of chemical substances in drinking water. Guideline Nr. 1 1992 from the Danish Environmental Protection Agency. In Danish.

MST (1992b). Industrial Air Pollution Control Guidelines. Guideline Nr. 9 1992 from the Danish Environmental Protection Agency.

Rowland M and Tozer TN (1995). Age and weight. In: Clinical pharmacokinetics. Concepts and applications. Third edition. Williams & Wilkins, 241-243.

VFD (1997). List of food additives to be used in foodstuffs. "Positivlisten". Danish Veterinary and Food Administration