ECPI Fact Sheet in Response to the Greenpeace Attack on the Use of Flexible PVC in Toys

Are Greenpeace correct in claiming that little is known of the type of phthalates used in PVC toys or of their extraction during use?

Flexible PVC has been used in the production of PVC toys for the past forty to fifty years. The plasticisers most commonly used have been di-(2-ethylhexyl) phthalate (DEHP, DOP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP). Due to their widespread use in a variety of different applications the toxicology of these phthalates has been extensively researched and understood.

It has long been recognised that children will suck and chew on everything with which they come into contact and that during this process they will extract and ingest substances. This is true irrespective of whether the material used is wood, rubber, PVC or other plastics. Consequently the potential for intake of a variety of substances, including plasticisers, from toys has been extensively investigated.

In 1985, for example, Rodricks and Turnbull (1) analysed an extensive collection of plasticiser migration data from PVC pacifiers, teethers and toys and concluded that the use of these products, when properly processed, did not pose a risk to health.

Is it true that phthalates cause cancer?

There is no evidence to suggest that phthalates can cause cancer in human beings. Since 1980 a large number of investigations have shown that feeding high levels (many thousand times greater than foreseeable exposure) of phthalates and other chemicals to rodents over their lifetime causes a large increase in microbodies in the liver called peroxisomes. This 'peroxisome proliferation' leads to the formation of liver tumours. However, when these chemicals are given to non-rodent species such as marmosets and monkeys (2, 3) (primates considered to be metabolically closer to humans), such peroxisome proliferation and liver damage is not seen.

On the basis of these differences in species response, it was concluded some years ago that phthalates do not pose a significant health hazard to people. This scientific view was adopted by a European Commission decision of 25 July 1990 which states that DEHP shall not be classified or labelled as a carcinogenic or irritant substance. The correctness of this decision has recently been reaffirmed by two comprehensive reviews (4, 5).

While the International Agency for Research on Cancer (IARC) has classified DEHP as "an agent possibly carcinogenic to humans", this is based only on the rodent studies and does not take into account the more recent understanding of the underlying mechanisms. It is possible that this classification will be open to change in the future following the recent publication of an IARC consensus report on peroxisome proliferation and its role in carcinogenesis.

Are Greenpeace correct in stating that there is emerging concern that phthalates can mimic oestrogen and may therefore be responsible for human reproduction problems?

The most recent in-vivo (live experimentation) studies specifically intended to look for oestrogenic effects are a series of internationally accepted and validated tests which measure changes in the reproductive organs of female rats which occur via processes under oestrogenic control. They have shown (6, 7, 8) that all the phthalates ranging from dibutyl phthalate (DBP) to diisodecyl phthalate (DIDP) produce no oestrogenic effects.

In addition, numerous multigeneration fertility studies have been carried out on many different phthalates. The most recent of these are 2-generation studies which demonstrate that exposure of rats to diisononyl phthalate (DINP) (9) and DIDP (10) in utero, during lactation, puberty and adulthood does not affect testicular size, sperm count, morphology or motility, or produce any reproductive or fertility effects. No outcome which might be anticipated from hormone modulation was observed. The maximum level dosed was around 600 mg/kg bw/day.

It is true that some laboratories using newly developed in-vitro (test tube) screening assays have shown some phthalates, such as dibutyl phthalate (DBP) and butylbenzyl phthalate (BBP), to exhibit a weak positive result indicating possible oestogenicity. However, these findings are equivocal in that these phthalates have proved to be non-oestrogenic in some studies (6, 11, 12, 13, 14). Most phthalates, including DEHP, diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), have been tested and found to produce no oestrogenic effects[11].

Recently published data from in-vitro screening tests (15) indicates that , in contrast to other studies (11, 13), DINP may be weakly oestrogenic. However these authors recognise that when plasticisers are eaten they are broken down to other molecules and that it is these to which humans are actually exposed. They have shown that these breakdown products are not active in the screening tests. They therefore conclude that results from in-vitro tests on whole phthalates may have little significance for human health and that it is the results of the tests on live animals (see above) which are important.

Is it true that there are a variety of materials which are safer to use than flexible PVC in toys?

As Greenpeace themselves point out this is not true. All materials contain substances which can be extracted by sucking or chewing however the majority of these substances have not been investigated to the same extent as phthalates.

Are Greenpeace correct in concluding that the weight of evidence indicates that flexible PVC should not be used in children’s toys?

The Greenpeace study only identifies the levels of phthalates in toys and does not provide any new toxicological or exposure data. They have not carried out a risk assessment of any kind and so the ‘weight of evidence’ statement is not supported by the data provided. It should be noted that, in line with the Existing Substances Directive, the major phthalates are currently being subjected to risk assessment by the competent authorities of Holland, France, Sweden and Norway. It is these independent risk assessments and not the Greenpeace ‘study’ which will decide which materials should be used.

REFERENCES 

1. Rodricks JV. And Turnbull D. "A Comprehensive Risk Assessment of DEHP as a Component of Baby Pacifiers Teethers and Toys" in "The Risk Assessment of Environmental and Human Health Hazards : a Text Book of Case Studies", John Wiley, 1989.

2. Rhodes, C., et al, 1986, Environ Health Perspect, 65, 299.

3. Short, R.D., et al, 1987, Toxicol Ind Health, 3, 185.

4. Ashby, J., Brady, A., Elcombe, C.R., Elliott, B.M., Ishmael, J., Odum, J., Tugwood, J.D., Kettle, S. and Purchase, I.F.H. 1994, ‘Mechanistically-based human hazard assessment of perixisome proliferator-induced hepatocarcinogenesis’, Human and Experimental Toxicology, 13, Supplement 2.

5. Huber, W.W., Grasi-Kraupp, B. and Schulte-Hermann, R., 1996, ‘Hepatocarcinogenic potential of di(2-ethylhexyl) phthalate in rodents and its implications on human risk’, Critical Reviews in Toxicology, 26(4), 365-481.

6. Meek M D, Clemons J, Wu Z F and Zacharewski T R (1996), 'Assessment of the alleged oestrogen receptor-mediated activity of phthalate esters', presented at the 17th Annual SETAC Meeting, Washington, USA, 18-21 November 1996.

7. Meek, M.D., Clemons, J., Wu, Z.F. and Zacharewski, T.R., 1997, ‘Examination of the alleged in-vitro and in-vivo ostrogenic activities of eight commercial phthalate esters’. Presented at the SETAC Europe Meeting, Amsterdam, 6-10 April 1997. Submitted for publication.

8. Uterotrophic assays in immature rats, Zeneca Central Toxicology Laboratory, Report Nos. CTL/R/1278 - 1281, 1996.

9. Nikiforov A I, Keller L H, Harris S B, 'Lack of transgenerational reproductive effects following treatment with diisononyl phthalate (DINP)', SOT 1996 Annual Meeting, Abstract 608 cited in Fundamental and Applied Toxicology Supplement, The Toxicologist, Vol 30, No 1, Part 2, March 1996.

10. Nikiforov, A.L., Trimmer, G.W., Keller, L.H., Harris, S.B., ‘Two-generation reproduction study in rats with diisodecyl phthalate (DIDP)’, presented at Eurotox’96, September 22-26 1996.

11. Balaguer P, Gillesby BE, Wu Z F, Meek M D, Annick J and Zacharewski TR (1996), 'Assessment of chemicals alleged to possess oestrogen receptor mediated activities using in-vitro recombinant receptor/reporter gene assays', SOT 1996 Annual Meeting, Abstract 728, cited in Fundamental and Applied Toxicology Supplement, The Toxicologist, Vol 30, No 1, Part 2, March 1996.

12. Jobling, S., Reynolds, T., White, R., Parker, M.G. and Sumpter, J.P., 1995, ‘A variety of environmentally persistent chemicals, including some phthalate plasticiers, are weakly oestrogenic’. Environmental Health Perspectives, 103 (6), 582-587.

13. Soto, A.M., Sonnenschein, C., Chung, K.L., Fernandez, M.F., Olea, N. and Serrano, F.O., 1995, ‘The E-screen assay as a tool to identify oestrogens: an update on oestrogenic environmental pollutants. Environmental Health Perspectives, 103 (7), 113-122.

14 Gaido, K.W., Barlow, K.D. and Leonard, L., ‘Use of a Yeast-based Oestrogen Receptor Assay to assess chemical interactions with the Oestrogen Receptor’, SOT 1996 Annual Meeting, Abstract 731 cited in Fundamental and Applied Toxicology, Supplement, The Toxicologist, Vol 30,No.1,Part 2, March 1996.

15. Harris, C.A., Pirkko Henttu, Parker, M.G. and Sumpter, J.P., 1997, ‘The estrogenic activity of phthalate zsters in vitro’. Environmental Health Perspectives, 105 (8), 802-811.