An Evaluation of the Hazards of Toys and other Products made from Polyvinyl Chloride (PVC)

A 1998 document of the Netherlands National Institute of Public Health and the Environment (RIVM) (excerpts)

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Summary

At the request of the Secretary of State for Health,Welfare and Sports a working group of representatives from interested parties has investigated the release of phthalates from soft PVC baby toys. Since di-isononylphthalate (DINP) appeared to be the phthalate predominantly used in soft PVC toys, only this phthalate was considered in detail in any further work. The following experimental studies have been carried out a human volunteers study to determine release rates of DINP from PVC samples into saliva (carried out by TNO Nutrition and Food Research Institute). a child observation study to determine the oral contact time of young children with baby toys (carried out by the Wageningen Agricultural University) a new assessment of the exposure of babies to DINP from soft PVC toys (carried out by RIVM)

development of a routine laboratory method to determine the release rate of DINP from soft PVC baby toys (carried out mainly by TNO Nutrition and Food Research Institute, with assistance from laboratories of other Consensus Group members) Based on the results from these studies and assuming that soft PVC baby toys are the most important source of exposure of babies to DINP, it is concluded that exposure levels of children >12 months were well below the maximal Tolerable Daily Intake (TDI) of 0.15 mg/kg/day, for the sample tested. For children of 3 - 12 months in rare cases the xposure

may approximate or exceed the TDI, if the sample tested would be representive for products on the market.

1. Introduction

In 1997 the Netherlands’ Health Protection Inspectorate (IGB) determined release rates of phthalates from baby toys. Like in some other countries considerable releases were found.

In a risk assessment carried out by the National Institute of Public Health and the nvironment (RIVM) the resulting uptake by young children was estimated to approximate or exceed the tolerable daily intake (TDI). Subsequently the Chief Inspector for Health Protection recommended retailers to voluntary withdraw soft PVC baby toys from the market. PVC producers, toy industry and retailers questioned the realistic nature of the data used for the risk assessment. In reaction the Secretary of State for Health, Welfare and Sports asked the RIVM to reach consensus with all interested parties (inspectorate, consumer groups, industry, retailers) on a method to assess the risk of the release of phthalates from baby toys, with special emphasis on a method to determine release rates.

2.2 volunteers study

It was accepted that it is impossible to carry out studies with young children for practical and ethical reasons. Therefore it was agreed to use adults as a surrogate. Differences in the way of chewing and sucking on toys between children and adults were not considered to introduce a significant error in the exposure estimate. The intra-individual variation in composition of saliva (in particular pH, proteins) between the volunteers did not have influence on the release rate of DINP. Differences in composition of saliva of children and adults might be more significant, but quantitative information was nog available and such differences were therefore ignored.

In the volunteers study the DINP content of saliva was used as the measure for the release rates from PVC. It appeared to be not technically feasible to determine quantitatively the amount adsorbed to the surface of the oral cavity. This could lead to an underestimation of the amount released and absorbed. On the other hand, young children do not swallow all saliva produced. Because these opposite influences could not be quantified, the consensus group decided to ignore them.

A summary of the results of the volunteers study can be found in Annex 2.

The average levels of release of specimens 1, 2 and 3 (of 1.4 g/min, 2.4 g/min and 1.6 g/min, respectively) correspond well. A possible explanation of the 50% higher releases of

specimen 2 is the different shape of this specimen, leading to a different interaction in the mouth during biting and sucking.

Overall, the consensus group found it acceptable to use the release rates as measured in the volunteers experiment as the best estimate of release rates in young children.

3. safety considerations

The TDI [tolerable daily intake] of DINP is 0.15 mg/kg/day

. A first estimate for the dietary exposure to phthalates is 0.023 mg/kg/day (source: footnote 1). No specific estimates are known for DINP. No estimate is available for other sources of exposure. It is not up to the Consensus Group to decide which fraction of the TDI should be reserved for exposure to baby toys. As a hypothesis, which should be tested, it is assumed that other sources of exposure are not higher than the exposure to food. This would leave a maximum acceptable uptake of DINP of approximately 0.1 mg/kg/day for maximum acceptable exposure to DINP from toys. This figure is provisionally used for further calculations in this report (the final choice of such a figure is left to policy makers). If the exposure data of specimen 2 presented in Annex 4 would be representative for all PVC toys, this limit can be exceeded in rare cases for children up to 12 months (so rare that the statistical likelihood cannot be estimated on the basis of the current data). In 99% of the cases the exposure would remain below 0.1 mg/kg/day. In 95% of the cases the exposure would remain under 0.04 mg/kg/day. For children > 12 months the risk is considerably lower and exceeding of the TDI is not observed.

For the interpretation of these data it should be emphasised that exceeding this level does not mean that a negative health impact will occur (because of the safety factors used in deriving the TDI), but only that the safety cannot be guaranteed.

4. policy implications

It is not the job of the Consensus Group to decide on the maximum acceptable release rates

for DINP in PVC for baby toys. We will try to give an outline, however, how the above data can be used for policy development based on the measurement of release rates, once the acceptable risk has been set by policy makers.

If the 99 percentile exposure levels are chosen as the reference for acceptable exposure levels, the exposure to DINP from specimen 2 is 75% of the assumed maximum acceptable exposure to DINP from toys. This corresponds with a release rate from specimen 3 (which is punched from the same toy) in the ‘head over heels’ extraction test of 3 g/min. The maximum acceptable release rate would therefore be theoretically 3/0.75 g/min = 4 g/min (if 0.1 mg/kg/day is used as the maximum acceptable exposure to DINP from toys).

Similar calculations can be made if 95 percentile or maximum exposure levels are chosen as the reference, or if a higher or lower fraction of the TDI is attributed to toys.

For safety purposes it is important to avoid false negatives when testing the release rates from toys. In practice, therefore maximum acceptable release rates should account for limitations of the reproducibility of a routine test method. An interlaboratory comparison study will be essential.

HUMAN VOLUNTEERS STUDY (SUMMARY REPORT)

W. Meuling and R. Rijk TNO Nutrition and Food Research Institute

Twenty volunteers were recruited for a study on the release of plasticizer from PVC baby

toys. The purpose of the investigation was to establish the release of plasticizers from PVC

under conditions as close as possible to daily use of plasticized materials by babies. The study has been conducted according to the ICH Guidelines for Good Clinical Practice. Test specimens

Three plasticized PVC specimens were included in the study

Specimen 1 = Disk (23 * 3 mm, total area 10 cm) of a standard PVC sample (prepared under controlled condition, containing 38.5% of diisononylphthalate (DINP)

Specimen 2 = Finger (exposed area 10 cm) of a commercial available teething ring Specimen 3 = Disk (23 * 2-4 mm, total area 10 cm) punched from a flat part of the

teething ring (specimen 2)

Control specimen = Disk (23 * 2.5 mm, total area 10 cm) of polytetrafluoroethylene (PTFE, Teflon)

Exposure conditions

Volunteers were instructed on biting and sucking procedure and delivery of total amount of saliva produced. According to the protocol all volunteers were invited to suck and bite on the control specimen for 10 or 15 min, in order to obtain blank saliva. After five minutes of rest all volunteers were exposed to test specimen 1 for a period of 15 min. After a rest period of 5 min the exposure procedure was repeated three times with the same specimen. The test specimens were rinsed shortly with water and used in each following exposure periods. In this way a blank and four portions of exposed saliva were collected.

Subsequently the volunteers were randomly divided in two groups of 10 persons. One group was exposed to specimen 2 and the other group to specimen 3 using the same procedure as for specimen 1. All participants completed the study. Saliva was tested for pH, volume (by weighing), total protein content and amount of DINP. For the determination of DINP in human saliva a method was applied based on extraction of DINP with an organic solvent and quantification by means of HPLC - UV detection at 225

nm. Each collected portion of saliva was analysed in two independent determinations. The

method was validated by standard addition of DINP to the blank saliva of each individual volunteer. DINP-values found in the saliva were corrected for recovery percentages.

Results

Overall mean values and standard deviation for each specimen and for the various parameters were calculated.

Table 1. Overview of results from in vivo tests.

Parameter Specimen 1 Specimen 2 Specimen 3

mean Sd/range mean Sd/range mean Sd/range

Saliva weight (g) 16.3 9.4 10.9 4.2 16.7 8.5

pH 7.31 0.12 7.26 0.16 7.38 0.11

Protein (mg/l) 497 126 539 189 463 122

DINP release (g/min) 1.38 0.3-8.3 2.44 0.9-8.9 1.63 0.9-5.7

From the results obtained it appeared that there is no influence from the pH and protein

content of the saliva, at the values observed for the volunteers. A significant influence on the total release of DINP in saliva was found from the volume of the saliva produced . however, taking the exposure time as the relevant parameter and expression of DINP release in g/min, then there appeared to be no influence on the total volume of saliva produced during the exposure time. It was noted that the saliva production during exposure to test specimen 2 was significantly reduced compared to the other specimens.

Release in time appeared to be rather consistent. Below the mean release arranged to exposure period are presented.

Table 2. Release rates over 15 minutes time intervals

Exposure Specimen 1 Specimen 2 Specimen 3

period mean (g/min) mean (g/min) mean (g/min)

0-15 min 1.50 2.88 1.79

20-35 min 1.16 1.96 1.45

40-45 min 1.29 2.46 1.50

50-65 min 1.57 2.46 1.79

 

Annex 3

MOUTHING BEHAVIOUR OF YOUNG CHILDREN; AN OBSERVATIONAL

STUDY (SUMMARY REPORT)

M.E. Groot, M.C. Lekkerkerk, L.P.A. Steenbekkers

Department of Household and Consumer Studies, Wageningen Agricultural University.

The aim of this study is to quantify mouthing behaviour of young children. By means of an

observational study the time is assessed that children lick, suck or bite on objects. Parents of children in the age between 3 and 36 months have observed their child during 10 times one quarter of an hour at two different days. During these quarters they have registered the time during which the child has put something into his/her mouth. In case of a toy they also

specified the kind of toy. Data of 42 children are obtained. The children are divided into 4 age groups, according to developmental period:

3 to 6 months (n=5);

6 to 12 months (n=14);

12 to 18 months (n=12);

18 to 36 months (n=11).

Five categories of objects are discerned: dummy/pacifier, teether, fingers, toys and non toys. The parents specified the toys involved. On the basis of this specifications the toys are divided into two groups: toys meant for mouthing and toys not meant for mouthing. This division is made according to the definition producers of toys give. It should be noted that parents make this division in another way. The total time of mouthing behaviour in the observational period is extrapolated to the time the child is awake and not involved in eating. This will be referred to as the ‘awake time per day’. This is the total time of a day that the child has the opportunity to put objects into the mouth. The results presented in figures 1 - 3 all concern these extrapolated times.

Table 1. Standard deviation, minimum, mean and maximum total mouthing time [minutes], excluding dummy.

standard deviation

minimum mean maximum

3-6 months 19.1 14.5 36.9 67.0

6-12 months 44.7 2.4 44.0 171.5

12-18 months 18.2 0 16.4 53.2

18-36 months 9.8 0 9.3 30.9

 

EXPOSURE ASSESSMENT (SUMMARY REPORT)

M.P. van Veen

RIVM/LBO

The assessment of exposure to DINP due to mouthing (licking, sucking and chewing) of soft PVC toys was estimated as follows. The following key parameters were obtained from

research or literature. 1. Duration of mouthing. Durations were established by research of Household Studies at the Wageningen Agricultural University (WAU) (Groot et al., in prep). The duration was calculated by summing all mouthing activities except sucking on dummies (meeting of begeleidingscommissie WAU-research, 20/8/98). Durations were expressed as seconds per day. Four age categories were discerned, 3-6 months (n=5), 6-12 months (n=14), 12-18 months (n=12), and 18-36 months (n=11). Each child was observed on two days. These days are separately taken into account. The distribution of durations includes therefore both inter- and intra-individual variance.

1. Leaching rate. In vivo leaching rates were established by research of TNO (Meuling, in prep.). The four samples per test series were all taken into account. Leaching rates were

expressed in g/minute, and for the present analyses recalculated to mg/minute. Leaching

rates were available for specimen 1 (n=20), for specimen 2 (n=10), and for specimen 3 (n=10).

2. Body weight. Age specific body weights were obtained from GVO (Groeiboek, p:1-96,

GVO Den Haag) and are given in table 1 and 2. Body weights are assumed to have a normal distribution.

The above parameters were brought into the ‘product leaching scenario’ of CONSEXPO 2.0

(Van Veen, 1997). Additional parameters are product volume and concentration for which a sensitivity analysis was performed. The model is not sensitive at all to these parameters,

implicating that the total amount of DINP is not limiting. The ‘product leaching scenario’ allows a probabilistic estimation of exposure. Essentially, the key parameters are represented by distributions. Duration and Leaching were expressed as empirical distributions from which subsequent random sampling took place. Body weight was

sampled as random normal number (as calculated from the random number generator ran1,

see Press et al., 1992 for details [Numerical Recipes in C, 2

press, Cambridge]). A Monte Carlo analysis was performed to establish the final exposure distribution. The measure of exposure is mg phthalate/kg body weight during a day that a child sucks or chews. Tables 1, 2, and 3 report the estimated dose of phthalates per age category. The dose is calculated for the mean parameter case and at various percentiles of the Monte Carlo exposure distribution. In addition the maximum value of the Monte Carlo analysis is given as ‘maximum’. In the mean parameter case, each parameter is not a distribution but is represented by its mean only. The exposure distributions for age category 2 (6-12 months) underlying the tables are depicted in figure 1, 2 and 3. Both distributions are very skewed, the medians (=50 percentile) are much lower than the means, and upper tail percentiles are a factor 5-10 larger than the median value.

Table 1. Dose of DINP from specimen 1.

dose (mg/kg bw), per age category

1 2 3 4

mean parameter

case

0.00811 0.00653 0.00194 0.000949

50 percentile 0.00572 0.00362 0.000823 0.000383

95 percentile 0.0207 0.0222 0.00867 0.00333

99 percentile 0.0463 0.0447 0.0185 0.00737

maximum 0.101 0.131 0.0825 0.0205

body weight 6.25 (0.5) kg 9.25 (1) kg 11 (1.25) kg 13.5 (1.5) kg

age 3-6 month 6-12 months 12-18 months 18-36 months

Table 2. Dose of DINP from specimen 2.

dose (mg/kg bw), per age category

1 2 3 4

mean parameter

case

0.0144 0.0116 0.00344 0.00167

50 percentile 0.0103 0.00678 0.00146 0.000748

95 percentile 0.0397 0.0389 0.0160 0.00640

99 percentile 0.0773 0.0753 0.0352 0.0126

maximum 0.112 0.204 0.0894 0.0302

body weight 6.25 (0.5) kg 9.25 (1) kg 11 (1.25) kg 13.5 (1.5) kg

age 3-6 month 6-12 months 12-18 months 18-36 months

Table 3. Dose of DINP from specimen 3.

dose (mg/kg bw), per age category

1 2 3 4

mean parameter

case

0.00966 0.00779 0.00233 0.00113

50 percentile 0.00717 0.00480 0.00106 0.000521

95 percentile 0.0260 0.0255 0.0105 0.00432

99 percentile 0.0398 0.0518 0.0220 0.00783

maximum 0.0707 0.142 0.0511 0.0230

body weight 6.25 (0.5) kg 9.25 (1) kg 11 (1.25) kg 13.5 (1.5) kg

age 3-6 month 6-12 months 12-18 months 18-36 months

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