Frequently Asked Questions

  • What are phthalates and what are they used for?

Phthalates are a group of colourless, odourless liquids which are used as 'plasticisers'. They are produced by the simple reaction of alcohols with phthalic anhydride and the elimination of water. Both alcohols and phthalic anhydride are well known substances which have been in use for a long time and which are derived from petroleum. Phthalates have very low volatility, do not readily dissolve in water and are not persistent in the environment. Their principal use is to soften the popular plastic, polyvinyl chloride (PVC). Plasticised PVC is used in a wide range of applications such as medical tubing and bloodbags, footwear, stationery goods, flooring and wall-coverings, electrical cable insulation, clothing and toys. 

  • What other products, apart from PVC, are phthalates used in?

Rubber products, paints, printing inks, adhesives, lubricants and some cosmetics. However, some 90% of all plasticisers are used in the production of flexible PVC. 

  • What amount of phthalates are used in Europe, and what are the principal ones?

In western Europe about one million tonnes of phthalates are produced each year of which more than 900,000 tonnes are used in the plasticisation of PVC. The most commonly used are diisononyl phthalate (DINP), di-2ethylhexyl phthalate (DEHP or sometimes called DOP) -  and diisodecyl phthalate (DIDP). For further information on these individual phthalates please refer to: The DINP Information Centre, the DEHP Information Centre, and the DIDP Information Centre.

  • Is it true that phthalates cause cancer?

No phthalates are classified as human carcinogens by the World Health Organisation (WHO) and 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 [13, 14] (primates considered to be metabolically closer to humans), such peroxisome proliferation and liver damage is not seen.
 
It is now generally accepted that phthalates are one of a number of substances which can cause liver tumors in rodents by a mechanism which does not occur in humans.
 
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 [15, 16].

In February 2000, the International Agency for Research on Cancer (IARC) - which is part of the World Health Organisation (WHO) - re-classified the phthalate plasticiser DEHP as "not classifiable as to carcinogenicity to humans." Some years earlier it had been classified as "possibly carcinogenic to humans" based on rodent students.

  • It has been said that phthalates are responsible for reduced sperm count in men and other human reproduction problems. Is this true?

It has been hypothesised (and at the moment it remains a hypothesis) that some reported cases of reduced sperm count in men may be due to exposure to chemicals in the environment which mimic the natural female hormone oestrogen. There is still no evidence that there is a general problem in humans and no evidence that chemicals in general, or any chemicals specifically, are the cause. However, this hypothesis has sparked interest in the development of screening tests which could be used to identify oestrogenic substances.
 
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 [17, 18, 19] 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) [20] and DIDP [21] 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.
 
In a 1995 publication Sharpe et al [22] hypothesised that the observed effects on rat testes after administration of a low dose of butylbenzyl phthalate (BBP) were related to an oestrogenic mechanism. In fact there are some inconsistencies in this study and therefore it is being repeated in other laboratories. One of these repeat studies [23] has been completed and shows no effects on testes at these low doses.
 
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 oestrogenicity. However, these findings are equivocal in that these phthalates have proved to be nonoestrogenic in some studies [17, 24, 25, 26, 27].
 
Most phthalates, including DEHP, diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), have been tested and found to produce no oestrogenic effects [24].
 
Recently published data from in-vitro screening tests [28] indicates that, in contrast to other studies [24, 26] , 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 which are important.
 
The potential reproductive risk posed by some phthalate esters has recently been reviewed by the Commission of the European Communities [26] . While it is the case that some phthalates have been shown to cause reproductive effects in rats and mice, these have occurred at levels 10,000 times higher than the estimated exposure to people. It is, therefore, very unlikely that any significant risk to human reproductive health is associated with the use of phthalates.
 
The hypothesis of the potential impact of industrial chemicals on animal and human health and fertility is, in fact, a question for the entire chemical industry. Cefic, the body which represents the European chemical industry, has responded to this broad debate and has already implemented a substantial programme of research. 

  • Is asthma linked to phthalate exposure?

All sorts of substances, materials and even specific elements of our modern lifestyle have come under the spotlight as far as asthma is concerned. Unfortunately it is an area where there is still little known about the causes. However, tests have been conducted on phthalates in the United States and have shown no evidence of them causing asthma. US authorities (National Academy of Sciences) have considered phthalates as a potential inducer of asthma and found the evidence unconvincing.

  • Phthalates are found in many household items and some of these items contain more than 50% phthalates.  Isn't this a cause for concern?

The amount of phthalates found in a finished product has little to do with potential exposure. That is entirely dependent on the amount that might migrate from the article which in turn is dependant on how the article is manufactured and how it is used. The fact is that, in the 50 years during which phthalates have been used, there is no reliable evidence that they have caused health problems for anyone when used as intended. The presence of phthalates in household items does not mean that they will enter the body at harmful levels.  Indeed, The CDC data report has demonstrated that real life exposure is within "safe" limits.

  • Recent evaluations have raised concerns about the use of DEHP in medical devices.  Shouldn't we at least limit that application?

DEHP-plasticized medical devices have become vital to modern healthcare.  DEHP-plasticized PVC is a popular choice for many medical applications because it is clear, affordable, strong, flexible, easily sterilized and won't kink. 

In Europe it is the only plasticiser recommended for use in blood bags by the European pharmacopoeia.

The US Food and Drug Administration recently issued a "Consumer Update" stating concern for very young male infants who are critically ill and have prolonged exposure to multiple devices containing DEHP."  However, whilst noting that studies have not been conducted which would rule out effects on humans it stated that DEHP-containing devices have been used on newborn babies for many years without apparent ill effect.  The FDA expressed little concern for adults receiving medical treatments such as intravenous or dialysis.  The concerns about possible risks are based on the effects seen in rodents.  However, tests on primates, which are much better predictors of effects of DEHP in humans than rodents, have demonstrated that they are much less susceptible to effects from DEHP than rodents.

Regulatory agencies in many countries that have approved DEHP-plasticized vinyl for use in medical devices make the point that substitutes may expose patients to hazards not present with devices made with DEHP.  Any alternative to DEHP in vinyl would have to undergo scientific scrutiny and receive approval from such authorities before it could be used.

The medical device industry is one of the most highly regulated in the world. All such products, including their components, therefore have to conform to rigorous safety standards.

For more information please refer to Plasticisers in Medical Devices and to the DEHP Information Centre

  • There have been newspaper reports that phthalates leach out of plastic water and soda bottles. Is this true?

Definitely not. Phthalates do not leach out of water or soda bottles because there are no phthalates in them to begin with.

Many such bottles are made from polyethylene terephthalate. Despite the similarity in name, they are very different.

  • The use of phthalates in a large number of everyday products such as cosmetics, toys, cables, etc must mean that we are being exposed to much higher levels than to those from just one substance. Isn't this a problem and shouldn't we be doing something about it?

Aggregating exposures is only valid for substances that act via additive mechanisms. For phthalates, there is no evidence to support the additive theory, and some evidence to refute it. It is clear that health effects that may be caused in animals by exposure to phthalates differ among the various compounds and depend on the timing and size of the dose. Not all phthalates act the same way, and none have acted at all on laboratory animals unless the dose is very large. So, arguing that phthalate exposures are additive is a good scare tactic, but not good science.

Misguided information and exaggeration of the facts is unfortunately commonplace among those who are trying to restrict the use of phthalates. Cosmetics are a good example.  People talk about 50,000 parts per million of a phthalate in nail polish being typical of the amount found. It may sound like a lot. It's five percent. Yet if a woman used and absorbed all of the dibutyl phthalate from five - 5 - full bottles of nail polish every day, her exposure would still be about equal to a level that produced no effects in laboratory animals.

For another example, the maximum concentration of diethyl phthalate in a recent survey of perfumes sampled was 2.8%. A woman would have to somehow spray herself with more than 2 litres of perfume daily, and absorb all the diethyl phthalate in that perfume, to exceed the amount that produced no effects in laboratory animals.

Further evidence that people are not being put at risk from exposure to phthalates comes from work conducted by the US Centers for Disease Control and Prevention (CDC). In studies they conducted on the levels of low-level metabolites of various chemicals in urine samples among human volunteers they found nothing alarming about the levels of phthalates. The levels were all within those considered safe by the US Environmental Protection Agency.

  • Is it right that phthalates are dangerous to the environment?

While phthalates are widely distributed in the environment, their levels are low because they are subject to relatively rapid photochemical and biological degradation. Levels of phthalates in natural waters are reported to be decreasing. The Netherlands National Institute of Public Health and Environmental Protection (RIVM) has reported that the level of phthalates in Lake Yssel fell by 75% in the period 1980-88 [1].
 
Over the past 40 years extensive research has been conducted into the environmental effects of phthalates and, as a result, the major phthalates are among the most well understood of all chemicals. There is now a large body of evidence to show that phthalates, at current and foreseeable exposure levels, do not pose a risk to human health or to the environment. 

  • There has been concern expressed about phthalates' toxicity in the water environment; what do you say to that?

It is worth re-stating that recent studies [l, 2, 3] show that levels of phthalates in natural waters are generally low and are reported to be decreasing. It is true that phthalates can accumulate in some simple aquatic organisms. However, most higher organisms (such as fish) are able to metabolise them (or break them down) rapidly without apparent harm and therefore, biomagnification up the food chain does not occur.
 
Well conducted aquatic toxicity studies [4, 5] which take into account the extremely low water solubility of phthalates, show that most phthalates do not exhibit acute or chronic toxicity to a variety of aquatic organisms. 

  • What about the spreading of municipal sewage sludge - which contains concentrations of phthalates - on agricultural land? Surely, phthalates can be taken up by plants and get into the human food chain that way?

There is no evidence to suggest that phthalates can enter the human food chain as a result of municipal sewage sludge being used on agricultural land. This is a subject which has been comprehensively studied over the years. In certain parts of Europe the spreading of sewage sludge on farmland remains an economic, effective and safe way of improving agricultural land.
  
There are two points to bear in mind: the rates at which phthalates biodegrade in sewage sludge and soils; and the uptake by plants from the ground of phthalates such as DEHP Phthalates are subject to both aerobic and anaerobic (in the presence, or not, of oxygen) biodegradation, and there are several investigations which demonstrate that when they are contained in sewage sludge they are rapidly biodegraded [6, 7, 8, 9, 10] 
 
For example, one study [11] examined garden soil containing DEHP. Within 20 days 75% of the phthalate had been degraded and after 30 days more than 90%.

A major research study on the uptake by plants of DEHP was conducted in the United States in 1989 [12]. Among the plants grown and tested were four food chain crops: lettuce, carrots, chili peppers and tall fescue (a pasture grass). The authors concluded that "because intact DEHP was not detected in any plants, DEHP uptake by plants was of minor importance and would not limit sludge additions to soils used to grow these crops".

  • With all of these issues facing the plasticiser industry, isn't it being complacent and insufficiently responsive?

The European plasticiser industry is very conscious of the genuine public concern which now exists around the use of phthalates. The Industry welcomes a responsible public debate, and accepts that it has a responsibility to respond to public concern by ensuring that there is an open exchange of information about the performance of its products. Clearly, if there was evidence that any single product presented a serious health risk, the plasticiser industry would have no hesitation in withdrawing it.

The industry is also fully committed to supporting and, where appropriate, commissioning further scientific research to give further comfort to the view that the current use of phthalates poses no hazard to the health of people or to the environment.

References

  1. National Institute of Public Health and Environmental Protection (RIVM), update of the Exploratory Report Phthalates', report no 710401008, Netherlands, 1991.
  2. Furtmann, K., 1993, 'Phthalate in der aquatischen Umwelt', Landesamt für Wasser und Abfall, NordrheinWestlaien, No6/93.
  3. Hurford N, Law, RJ, Payne, AP, Fileman, TW, 1989, Oil Chem Pollut 5, 391-410
  4. Rhodes, JE, Adams, WJ, Biddinger, GR, Robillard, KA and Gorsuch, JW, 1995, Env Toxicol and Chemistry, 14, 11, 1967.
  5. Adams, WJ, Biddinger, GR, Robillard, KA and Gorsuch, JW, 1995, Env Toxicol and Chemistry, 14,9,1569.
  6. Saeger, VW and Tucker, Ill, ES, 1976, 'Biodegradation of phthalic acid esters in river water and activated sludge', Appi Environ Microbiol, 31, 29, 34.
  7. Shanker, R, Ramakrishna, C and Seth, PK, 1985, 'Degradation of some phthalic acid esters in soil', Environ Poll, 39, 1-7.
  8. Fairbanks, B.C., O'Connor, GA and Smith, SE, 1985, 'Fate of di-2-(ethylhexyl)phthalate in three sludge amended New Mexico soils', J Environ Qual, 14(4), 479/483.
  9. Schnitzer, JL., Scheunert, L, Korte, F., 1988, 'Fate of Bis(2-ethylhexyi) [14C] phthalate in laboratory and outdoor soil-plant-systems', J Agr Food Chem 36, 210/215.
  10. Herring, R and Bering, CL, 1988, 'Effects of phthalate esters on plant seedlings and reversal by a soil micro-organism', Bull Environ Contam Toxicol, 40, 626-632.
  11. Shanker, R, Ramakrishna, C and Seth, RK., 1985, 'Degradation of some phthalic acid esters in soil', Environ Poll, 39, 1-7.
  12. Aranda, JM, O'Connor, GA and Eiceman, GA, 'Effects of sewage sludge on di-(2-ethylhexyl) phthalate uptake by plants', 1989, J Environ Qual 18, 45-50.
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  14. Short, RD, et al, 1987, Toxicol lnd Health, 3, 185.
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  16. Huber, WW, 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.
  17. Meek MD, Clemons J, Wu Z F and Zacharewski T R (1996), 'Assessment of the alleged oestrogen receptormediated activity of phthalate esters', presented at the 17th Annual SETAC Meeting, Washington, USA, 18-21 November 1996.
  18. Meek, MD, Clemons, J, Wu, ZF and Zacharewski, TR, 1997, 'Examination of the alleged in-vitro and invivo ostrogenic activities of eight commercial phthalate esters'. Presented at the SETAC Europe Meeting, Amsterdam, 6-10 April 1997. Submitted for publication.
  19. Uterotrophic assays in immature rats, Zeneca Central Toxicology Laboratory, Report Nos. CTL/R/1278 - 1281, 1996.
  20. Nikiforov A 1, 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.
  21. Nikiforov, AL, Trimmer, GW, Keller, LH, Harris, SB, 'Two-generation reproduction study in rats with diisodecyl phthalate (DIDP)', presented at Eurotox'96, September 22-26 1996.
  22. Sharpe, RM, Fisher, JS, Millar, MM, Jobling, S and Sumpter, JP 1995, 'Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production'. Environmental Health Perspectives, 103 (12), 1136-1143.
  23. Ashby, J., Tinwell, H., Lefevre, RA., Odum, J., Paton, D., Millward, S.W., Tittensor, S. and Brooks, A.N., 'Normal sexual development of rats exposed to butyl benzyl phthalate from conception to weaning'. Submitted for publication in Reg. Tox. Pharmacol.
  24. Balaguer, P, Gillesby, B.E., 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.
  25. Jobling, S, Reynolds, T, White, R, Parker, MG and Sumpter, JR, 1995, 'A variety of environmentally persistent chemicals, including some phthalate plasticiers, are weakly oestrogenic'. Environmental Health Perspectives, 103 (6), 582-587.
  26. Soto, AM, Sonnenschein, C, Chung, KL, Fernandez, MF, Olea, N. and Serrano, FO, 1995, 'The E-screen assay as a tool to identify oestrogens: an update on oestrogenic environmental pollutants. Environmental Health Perspectives, 103 (7), 113-122.
  27. Gaido, KW, Barlow, KD, 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.l,Part2, March 1996.
  28. Harris, CA, Pirkko Henttu, Parker, MG and Sumpter, JP, 1997. 'The estrogenic activity of phthalate esters in-vitro'. Environmental Health Perspectives, 105 (8), 802-811.
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  30. Rodricks, JV and Turnbull, D in 'The Risk Assessment of Environmental and Human Health Hazards: a text book of case studies', John Wiley, 1989.