Exposure of children and unborn children to selected chemical

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Exposure of children and unborn children to selected chemical

Transcript Of Exposure of children and unborn children to selected chemical

Exposure of children and unborn children to selected chemical
Survey of chemical substances in consumer products No. 158 April 2017

Publisher: Danish Environmental Protection Agency
Editors: Poul Bo Larsen, DHI Julie Boberg, DTU Food Pia Brunn Poulsen, Force Thit Aarøe Mørck, DHI Helle Buchardt Boyd, DHI Dorthe Nørgaard Andersen, DHI Marta Axelstad, DTU Food Ulla Hass, DTU Food
ISBN: 978-87-93529-84-7
Disclaimer: When the occasion arises, the Danish Environmental Protection Agency will publish reports and papers concerning research and development projects within the environmental sector, financed by study grants provided by the Danish Environmental Protection Agency. It should be noted that such publications do not necessarily reflect the position or opinion of the Danish Environmental Protection Agency. However, publication does indicate that, in the opinion of the Danish Environmental Protection Agency, the content represents an important contribution to the debate surrounding Danish environmental policy.
Sources must be acknowledged.
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Summary and conclusion






Background and objective



Implementation of the project



Preliminary selection of substances with endocrine disrupting,

suspected endocrine disrupting or neurotoxic effects



Overall strategy for selection of substances for risk assessment in the project 21


Strategy for selection of endocrine disruptors and suspected endocrine




Selection of endocrine disruptors and suspected endocrine disruptors


2.3.1 Discussion of data



Strategy for selection of neurotoxic substances



Selection of neurotoxic substances


2.5.1 Discussion of data



Selection of data for exposure assessment



Strategy for collection of exposure data



Presentation of exposure data from the literature



Discussion of data


3.3.1 Knowledge of the exposure of the substances based on biomonitoring data



Knowledge gaps and suggested analysis



Regulation of the selected substances






Overview of regulation in individual areas


4.2.1 Harmonised CLP classification


4.2.2 Regulation in relation to REACH


4.2.3 Regulation in the food area


4.2.4 Regulation in the cosmetics area


4.2.5 Regulation of substances in toys


4.2.6 Regulation, biocides/ pesticides


4.2.7 Regulation, limit values


4.2.8 Regulation, medicines


4.2.9 Overall assessment



Analysis of selected substances in selected products



Background for selection of substances and product types



Identification and purchase of specific products


5.2.1 Pizza boxes


5.2.2 Cosmetic products



Selection and description of analyses


5.3.1 Pizza boxes


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5.3.2 Cosmetic products



Analytical results


5.4.1 Pizza boxes


5.4.2 Cosmetic products



Exposure assessments






Exposure assessments, children under 3 years



Exposure assessments, pregnant women/ unborn children



Observations in connection with the exposure tables


6.4.1 Food exposure


6.4.2 Exposure via the environment


6.4.3 Cosmetics


6.4.4 Exposure from other consumer products



Exposure assessment from biomonitoring data



Exposure assessments based on analyses in Chapter 5


6.6.1 Exposure to BHT and BHA from cosmetic products


6.6.2 Exposure to bisphenols and phthalates from pizza boxes



Hazard Assessment of the selected substances



Objective and method


7.1.1 Method for hazard assessment of endocrine disrupting and suspected

endocrine disrupting substances


7.1.2 Method for hazard assessment of neurotoxic substances


7.1.3 Use of assessment factors


7.1.4 Hazard characterisation and DNEL for endocrine disruptors and suspected

endocrine disruptors


7.1.5 Hazard characterisation and DNEL for neurotoxic substances



Use of the DNEL values



Risk assessment






Risk assessment for endocrine disrupting effects


8.2.1 Cumulative risk assessment for endocrine disruptors (RCRtotal for medium

and high exposure)


8.2.2 Antiandrogenic substances


8.2.3 Estrogenic substances


8.2.4 Thyroid hormone disrupting substances


8.2.5 Risk Assessment in connection with analysed content of BHA and BHT in



8.2.6 Risk assessment in connection with analyses of bisphenol A and phthalates

in pizza boxes


8.2.7 Biomonitoring data


8.2.8 Discussion of assessment of endocrine disruptors


8.2.9 Discussion of findings for individual endocrine disruptors


8.2.10 Overall assessment of sources contribution to the risk for endocrine

disrupting effects

118 Most important substances

118 Knowledge base

121 Regulation

121 Grouping



Risk of chronic neurotoxic effects


8.3.1 Cumulative risk assessment for neurotoxic substances (RCRtotal)


8.3.2 Individual substances, children under 3 years


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8.3.3 Individual substances, pregnant women/ unborn children


8.3.4 Special scenarios


8.3.5 Biomonitoring data


8.3.6 Risk assessment in connection with analyses for bisphenol A in pizza boxes 126

8.3.7 Discussion of findings for the individual neurotoxic substances/ substance



8.3.8 Overall assessment of risk sources for neurotoxic effects

134 Most important substances

134 Knowledge base

136 Regulation



Discussion and conclusion










Appendix 1


Appendix 2


Appendix 3


Appendix 4


Appendix 5


Appendix 6a


Appendix 6b


Appendix 6c


Appendix 7a


Appendix 7b


Appendix 8


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This project is part of the wish of the government and “Enhedslisten” to safeguard children and young people from harmful and unnecessary chemistry. This project focuses on the existing knowledge of exposure of children and unborn children to endocrine disrupting substances (including suspected endocrine disrupting substances) and/or substances that are harmful to the nervous system. The objective is to establish whether individual sources that pose a risk to children and pregnant women/ unborn children can be identified, or whether the total exposure to substances with identical effects from multiple sources may cause a risk. At the same time, it is the intention that the project should benefit from the large amount of data obtained from the studies conducted under the Environmental Protection Agency's child chemistry package. The project was carried out between March 2016 and December 2016 in collaboration between DHI and the DTU Food Institute. A working group has been assigned to the project, consisting of: Shima Dobel, Danish EPA (project responsible) Bettina Ørsnes Larsen, Danish EPA (project responsible) Marie Louise Holmer, Danish EPA Charlotte Legind, Danish Veterinary and Food Administration Mette Holm, Danish Veterinary and Food Administration Julie Boberg, DTU Food Pia Brunn Poulsen, Force Poul Bo Larsen, DHI (project manager)
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Summary and conclusion
Objective and starting point The overall objective of this project is to assess whether there may be a risk of the overall exposure of children under 3 years and pregnant women/ unborn children to endocrine disrupting substances (including suspected endocrine disrupting substances) and chronic neurotoxic substances. The project was implemented in the following steps:
 Identification of endocrine disrupting, suspected endocrine disrupting and chronic neurotoxic substances to which children under 3 years and pregnant women/ unborn children may be potentially exposed.
 Collection of relevant literature to assess the exposure to the substances, including relevant biomonitoring data.
 Description of exposure/ exposure scenarios for the individual substances for children under 3 years and pregnant women/ unborn children.
 Hazard assessment of the identified substances and determination of tolerable exposure levels (derived no effect levels, DNELs) for each substance.
 Assessment of risk in relation to the estimated exposure and an assessment of risk by simultaneous exposure to several substances with the same mode of action.
 Discussion of the risk assessments and identification of substances with highest impact in relation to risk for endocrine disruption and chronic neurotoxic effects.
The project also includes an analytical program to fill out knowledge gaps identified in the exposure assessment in order to obtain a better basis for the risk assessment of these substances. Furthermore, a condensed regulatory status and overview is given for the identified substances of concern.
As the intention of the project is to include as many substances as possible to illustrate the overall exposure, the starting point is as far as possible to use existing assessments or reviews of the identified substances, e.g. assessments by the European scientific expert groups/ committees regarding assessment of chemical substances in foods, cosmetics and consumer products. Next, the aim is to apply the knowledge that during many years of efforts has been accumulated in the Environmental Protection Agency from the many surveys and investigation projects, including the LOUS projects. Not least, the following projects have been relevant for the preparation of this project: ”Survey and Health Assessment of the exposure of 2 year-olds to chemical substances in Consumer Products” (Danish EPA 2009); ”Exposure of pregnant consumers to suspected endocrine disruptors” (Danish EPA 2012a) and ”Survey and risk assessment of toluene and other neurotoxic substances in children´s rooms” (Danish EPA 2016a).
Identification of substances with endocrine disrupting and neurotoxic effects The identification of endocrine disruptors, suspected endocrine disruptors and known neurotoxic substances in this project is based on information collected by the Environmental Protection Agency as well as knowledge from the scientific literature. The identification/ selection phase includes an initial qualitative assessment of whether the exposure to a substance of concern for the identified target groups was considered realistic. In the selection of the substances, emphasis is primarily on the inclusion of substances for which there is sufficient evidence of the substance's harmful effects on the endocrine system and/ or the nervous system, so that the toxicological background data on the substances can form the basis for a subsequent hazard assessment and risk assessment. The Danish proposal for criteria for identifica-
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tion of hormone disrupting substances from 2011 is used in this project to determine if a substance is an endocrine disruptor or a suspected endocrine disruptor (Danish EPA 2011a). In the following, the wording “hormone disrupting substance” is used as an overall term for the groups of substances that are either “suspected hormone disrupting substances” or “hormone disrupting substances” according to these criteria. This process means that only a subset of neurotoxic, suspected endocrine disruptors and endocrine disruptors have been evaluated in the project. Thus, a number of endocrine disruptors and suspected endocrine disruptors have been identified but deselected for the risk assessment for a number of reasons, as described in Appendix 2. For example, for several groups of substances, indications of endocrine disrupting potential have been found, but sufficient data have not been found to determine the DNEL. This applies to several brominated flame-retardants, perfluorinated substances and some phenols. A number of pesticides with suspected endocrine disrupting potential are omitted because of low exposure, while some individual substances having suspected endocrine disrupting potential have been omitted because the mode of action was not considered suitable for grouping with antiandrogenic, estrogenic or thyroid hormone disrupting substances.
The terms "suspected endocrine disrupting" and "endocrine disrupting" substances reflect how strong the evidence is for endocrine disrupting effects of a substance. The Danish proposal for criteria for the identification of endocrine disrupting potential from 2011 is used in this project (Danish EPA 2011a). In this report, the term "endocrine disruptors" is used for the total group of substances that is either "suspected endocrine disrupting" or "endocrine disrupting" according to these criteria. Similarly, some well-known neurotoxic substances have also been deselected. This has been done either because they are considered not relevant to this project (methanol, ethanol, and manganese), or because it is not considered possible to conduct a risk assessment of the substances, as there is no precise knowledge on the dose-response relationship and NOAEL/ LOAEL regarding their neurotoxic effects for the substances (e.g. arsenic, fluoride and particulates (air pollution)). The justification for these deselections is specified in Appendix 3. Overall, 37 substances were included regarding endocrine disrupting effects and 39 substances regarding chronic neurotoxic effects, with some overlap (7 substances) between the groups.
Exposure data The available exposure data collected are as far as possible divided into the different sources of exposure:
 food items including drinking water  indoor environment (dust, vapours) + outdoor environment (soil)  cosmetics  consumer products (articles, toys, chemical products, etc.)  In relation to food exposure it is characteristic that the entire population is exposed to a greater or lesser extent, and therefore, a risk assessment based on food exposure cover a large fraction of the entire population and any specific subgroups (this may be data on different age groups or groups with different food preferences). Such representative data as for food exposure is only rarely available for the indoor environment and the outdoor environment. The report's estimates for indoor environment/ outdoor environment must therefore be considered with greater caution as the contribution from the indoor environment can be very variable and depends on many factors, such as the age of the building, building materials used, furniture, and activities of the residents. For the outdoor environment, polluted soil will typically be important for the exposure of children under 3 years.
For cosmetics, just as for foods, any consumption/use of the product also leads to exposure to the ingredients contained in the product. Knowledge of substance content in a cosmetic prod-
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uct and knowledge concerning use will give a fairly accurate indication of the exposure of the individual consumer. The degree of public exposure will to a greater extent than food exposure be determined by preference, as the use of cosmetics varies much in the population, i.e. some may not use other cosmetics than toothpaste and soap/ shampoo, while others have a high consumption of various cosmetic products.
Exposure from consumer products is as for cosmetics highly dependent on consumer preferences in relation to the purchased products, as well as the way they are used. The exposure estimates for consumer products are thus largely based on various assumptions, as the methodology for exposure estimation for consumer products are substantially less standardised than for foods and cosmetics. The exposure estimation often includes series of assumptions, each of which is subject to various degree of uncertainty.
Thus, from the collected data, the exposure for the individual substances is specified for each of the above sources, and the total exposure is calculated for the target groups, i.e. for children under 3 years and for pregnant women/ unborn children. Both medium exposure (characterised by the typical consumer exposure, e.g. an average or median exposure) and high exposure (i.e. an upper but realistic exposure such as a 95-percentile level) are calculated for the substances as far as possible. In addition, for some substances data could be obtained for specific exposure scenarios, typically worst-case scenarios, which are assessed separately from the other exposure.
In comparison with exposure estimations based on calculation models, biomonitoring studies containing exposure estimates were collected as well. Here the focus was on biomonitoring studies conducted in Denmark or from neighboring/ comparable countries and on studies in which the data has been converted to external daily exposure.
When reviewing these studies, estimation of exposure levels based on urine measurements were found for acrylamide, bisphenol A, phthalates (DEHP, DBP, DIBP, BBzP, DINP), triclosan and the UV filter BP-3, respectively. Especially for phthalates, there are highly relevant biomonitoring studies in both children and adults, where exposure estimates based on the measured data are indicated. These, together with the modelled exposure calculations, will help to provide a more complete picture of the exposure of the population groups. For biomonitoring studies with urine data, it was observed that the detected measurements in general result in comparable or lower exposure estimates than the exposure estimates based on the modelled calculations for assessment of exposure from the different sources.
For biomonitoring studies in media other than urine, e.g. in breast milk these data resulted in high exposure levels for breastfed infants. Exposure estimations in these studies are based on the measured concentration of breast milk coupled with the intake amount of breast milk for infants, and this indicates that breastfeeding can be a significant source of exposure. Also, this type of exposure may be compared to exposure for non-breastfed infants where the exposure estimation relies on the modelled data based on content in food items and other sources. Thus, biomonitoring based exposure estimations for perfluorinated substances, for tetra-BDE47, penta-BDE-99 and for totalPCB (sum of 7 PCB congeners) resulted in higher exposure via breast milk compared to alternative scenario regarding modelled exposure via food items. As the studies are not based on data from Danish mothers, they may not be directly transferable to the Danish population, but still they indicate that infants who are breastfed may be subjected to high exposure to substances that have accumulated in the mother. However, there are important benefits from breast feeding infants and these are generally considered to outweigh a potential risk from the chemical exposure.
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Hazard assessment, determination of DNEL It is necessary to have knowledge of dose-effect relationships for the neurotoxicity and/ or endocrine disrupting effects of the substances, in order to calculate a tolerable human exposure level (DNEL value) based on a NOAEL or LOAEL (or a benchmark dose) using assessment factors in accordance with the guidelines for their use. As for exposure estimation, uncertainties and limitations have to be considered as well when determining DNEL values.
For endocrine disruptors, all DNELs are determined based on animal studies. The basis for the calculation of DNEL is dependent on experimental design, choice of doses and investigated endpoints. Thereby the determined DNEL values could be changed with increased knowledge base. For neurotoxic substances, the starting points for DNEL calculation are very different. In one case, DNEL is determined based on a single limited study on newborn mice, where the behaviour of the animals is evaluated. In another case, DNEL calculation may be based on IQ testing of thousands of children and relationships between e.g. levels of lead in the blood and the IQ level of the children. Although a numerical DNEL value for both types of data may be obtained, a DNEL obtained from a large population of people exposed at different levels of course is of greater relevance and strengthen the validity of the risk assessment.
In addition, it is worth noting that the tolerable exposure levels are typically lower the more knowledge that have been obtained for a substance and its effects. For instance, the tolerable exposure levels over the years have been reduced in connection with the increasing knowledge for substances such as lead, mercury, dioxins/ PCB, acrylamide and bisphenol A.
For endocrine disruptors, it is currently discussed whether a lower limit on the effects of endocrine disruptors can be determined with reasonable certainty (whether there is a threshold value for the effects) and thus, whether robust tolerable exposure levels (DNELs) can be deduced. As an alternative method to assess the risk of exposure to endocrine disrupting substances has not yet been developed, a traditional risk assessment approach is used here as described below. An advantage of this approach is that the risk of the combined exposure to multiple substances with the same modes of action can be calculated. If in future an agreement can be reached on alternative ways to assess the risk of endocrine disruptors, the calculations in this report should be reviewed. Such alternative risk assessment methods will be expected to result in lower DNEL values and thus higher calculated risk.
Risk assessment In order to assess risk for a substance, there must be data to conduct both exposure assessments and hazard assessments. Risk assessments for 34 substances regarding endocrine disrupting effects and 29 substances regarding chronic neurotoxic effects could be carried out, corresponding to 56 substances, as there was an overlap of 7 substances between the groups. For the risk assessment, the risk characterisation ratio, RCR, is calculated based on the ratio between the overall exposure to the substance from all sources and the tolerable exposure level (DNEL):
RCR = exposure (µg/kg/d) / DNEL (µg/kg/d)
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