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Phthalates

Uses

  • Phthalates have been used as plasticisers in many plastics since the 1930's, with a quarter of the total plasticiser ever produced being diethylhexylphthalate (Kirk-Othmer's Encyclopaedia). In the UK they are no longer used in the manufacture of cling film or most other food contact plastics (MAFF, 1996a).
  • The ink used to print on plastic, board and foil-packed products frequently contains phthalates, as do some of the adhesives used in packaging (MAFF, 1996a).
  • They are found in products such as baby milk formula, cheese, margarine and crisps ('chips' in the USA).
  • Also found in vinyl flooring, emulsion paint and PVC baby toys.
  • Phthalates used include diethylhexylphthalate (DEHP), monoethylhexylphthalate (MEHP), dimethylphthalate(DMP), butylbenzylphthalate (BBP), dibutylphthalate (DBP) and dioctylphthalate(DOP).

Toxicity

Phthalates are fat soluble, so tend to concentrate in materials such as butter, margarine and cheese. In addition, they are likely to accumulate in body fat.

Occupational exposures

Several phthalates, particularly DEHP, are testicular toxicants. Part of this toxicity is believed to involve depletion of testicular Zinc, and may include the death and disintegration of the testicular germ cells (Amdur et al., 1991; Peters et al., 1997).

Occupational exposure to high levels of phthalates has been reported to lead to miscarriages and other complications of pregnancy (IEH, 1995)

In vitro experiments

BBP is oestrogenic in the E-SCREEN assay, which uses a human breast cancer cell culture, MCF-7 (Soto et al., 1995). Both BBP and DBP were oestrogenic to a different breast cancer cell line, bound rainbow trout oestrogen receptor and initiated the transcriptional activity of the oestrogen receptor (Jobling et al., 1995). Both BBP and DBP were agonists of the oestrogen receptor - their action is cumulative, adding to any oestrogen already present.

BBP can also act as an antiandrogen, blocking the action of dihydrotestosterone in a yeast screen containing a human androgen receptor (Sohoni and Sumpter, 1998). In this screen BBP was approximately as potent as flutamide, a well known anti-androgenic chemical.

In vivo experiments

Research at the Chemical Industry Institute of Toxicology confirmed that DBP does damage the reproductive system of male rats at low exposures, however this research suggested that DBP was disrupting the androgen system rather than imitating oestrogen (Foster, 1997). Further research has established that DBP cannot bind the androgen receptor, but does disrupt androgen-regulated male sexual differentiation (Mylchreest et al., 1999). This research, funded by the chemical industry, demonstrates that DBP is an endocrine disrupter, though maybe not an oestrogen.

Both DBP and DEHP caused irregularities in male sexual differentiation when given to pregnant rats (Gray et al., 1999). DEHP caused testicular and epididymal abnormalities, whilst in a multigenerational study DBP caused malfunctions including retained nipples and hypospadias.

Human Exposure

From toys

Many teethers and soft toys contain phthalate plasticisers, and research has shown that these plasticisers can leach out of the toys into the mouths of the children chewing them. There is now a huge international debate on the safety of these toys and their alternatives. Much of the work has been carried out by Greenpeace; their initial campaign information is here. The EU Scientific Committee on Toxicity, Ecotoxicity and the Environment has produced several reports on the subject, which are available on their web site.

From household goods

The phthalate diethylhexylphthalate (DEHP) is used in many PVC building materials, for example PVC flooring. Researchers have found that DEHP, and other phthalates, are present on household dust, so will be inhaled by both children and adults. Infants breath twice as much air as adults (per kilo body weight), and spend most of their time indoors, so will be getting a particularly large dose of phthalates from dust (Oie et al., 1997). Disturbingly, animal experiments indicate that MEHP, a metabolite of DEHP can irritate lungs (Doelman et al., 1990). Other research suggests that there is an association between PVC flooring and the development of bronchial obstruction in children (Jaakkola et al., 1999). This research suggests that the increasing incidence of asthma could be partially due to the increasing household use of plastics containing phthalates over the last few decades.

In healthcare

Many of the bags and tubes used in hospitals are made of PVC and leach phthalate plasticisers. There's a lot of information on this subject at the Health Care Without Harm site.

In food

A major human exposure to phthalates is believed to be from foods which have absorbed the chemical from their packaging, or from manufacturing processes. The UK Ministry of Agriculture, Fisheries and Food have done a range of studies on foods:

Baby milk

In a study of formula baby milk published in 1996 all 15 brands of baby milk formula tested by the UK Ministry of Agriculture, Fisheries and Food contained phthalates. The highest total phthalate concentration found was 10.2 mg/kg, and the highest concentration of BBP found was 0.25 mg/kg. Using the manufactures' feeding guides it was estimated that a new born infant would receive , on average, 0.13 mg/kg body weight/day of total phthalate, falling to 0.10 mg/kg/day at 6 months (MAFF, 1996b).

However, a more recent MAFF survey, published in December 1998, found levels ten times lower. It is not clear what the reason for this is - it could include improved production techniques, or possibly changes in analytical technique (ENDS, 1998; the MAFF report is on the web here).

Other food

MAFF studies have found that phthalate levels in foods like crisps, chocolate bars and cheeses are in the tens of mg per kg range. The highest level found in dairy produce was 114 mg/kg in soft cheese (ENDS, 1995).

Phthalates, particularly DBP and DEHP, were also found in products packaged in paper and board, such as cakes, fats and confectionery. The highest concentrations of DBP found were in gravy granules (62 mg/kg), vegetable burger mix (10 mg/kg), vegetable fat (8.4 mg/kg), chocolate coated cakes (5.8 mg/kg) and sausages (4.4 mg/kg). The highest concentrations of DEHP were 25 mg/kg in cookies and 11 mg/kg in vegetable fat (MAFF, 1995).

A survey of phthalate levels in fatty food samples taken as part of a 'Total Diet Survey' in 1993 found phthalates to be present in every sample, including in meat, fish, eggs, milk and milk products. These analyses led to a prediction that the daily intake of phthalates by an adult averaged 0.8 mg/person/day (0.013 mg/kg body weight/day), up to 1.6 mg/person/day (0.027 mg/kg body weight/day) for someone with a diet high in phthalate-containing products (MAFF, 1996a).

In water

Due to their persistence in the environment, phthalates are also commonly found in groundwater, rivers and drinking water (Jobling et al., 1995). Researchers in Holland have found up to 3.5 micro-g/l of DEHP in drinking water (ENDS, 1999).


This page was last updated in October 1999
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References

Amdur et al. 1991. Casarett and Doull's Toxicology: The Basic Science of Poisons, 4th Ed., p499.

Doelman, C. J. A., Borm, P. J. A. and Bast, A. 1990. Plasticisers and bronchial hyperreactivity. The Lancet 335, p725.

ENDS 1995. Packaging industry failing to act over phthalates in food. ENDS Report 245: 7-8.

ENDS 1996. Denmark takes lead in curbs on oestrogenic chemicals. ENDS Report 252: 35-36.

ENDS 1998. Food industry blames MAFF for phthalate scare. ENDS Report 287: 12-13.

ENDS, 1999. Industry glimpses new challenges as endocrine science advances. ENDS Report 290, p26-30.

Foster, P. M. D. 1997. Assessing the effects of chemicals on male reproduction: Lessons learned from di-n-butyl phthalate. Chemical Industry Institute of Toxicology.

Gray, L. E., Wolf, C., Lambright, C., Mann, P., Price, M., Cooper, R. L. and Ostby, J. 1999. Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p, p'-DDE, and ketonazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicology and Industrial Health 15, p94-118.

IEH 1995. Environmental oestrogens: Consequences to human health and wildlife. Institute for Environment and Health, Leicester, UK.

Jaakkola, J. J. K., Øie, L., Nefstad, P., Botten, G., Samualsen, S. O. and Magnus, P. 1999. Interior surface materials in the home and the development of bronchial obstruction in young children in Oslo, Norway. American Journal of Public Health 89, p188-192.

Jobling, S., Reynolds, T., White, R., Parker, M. G. and Sumpter, J. P. 1995. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ. Health Persp. 103(Suppl. 7): 582-587.

Kirk-Othmer's Encyclopaedia of Chemical Technology, 3rd Ed.. Vol.18.

MAFF 1995. Food Surveillance information sheet number 60: Phthalates in paper and board packaging. UK Ministry of Agriculture, Fisheries and Food.

MAFF 1996a. Food surveillance information sheet number 82: Phthalates in food. UK Ministry of Agriculture, Fisheries and Food.

MAFF 1996b. Food surveillance information sheet number 83: Phthalates in infant formulae. UK Ministry of Agriculture, Fisheries and Food.

Mylchreest, E., Sar, M., Cattley, R. C. and Foster, P. M. D. 1999. Disruption of androgen-related male reproductive revelopment by di(n-butyl) phthalate during late gestation in rats is different from Flutamide. Toxicology and Applied Pharmacology 156, p81-95.

Øie, L., Hersoug, L.-G. and Madsen, J. Ø. 1997. Residential exposure to plasticizers and its possible role in the pathogenesis of asthma. Environmental Health Perspectives 105, p972-978.

Peters, J. M., Taubeneck, M. W., Keen, C. L. and Gonzalez, F. J. 1997. Di(2-ethylhexyl)phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-alpha. Teratology 56: 311-316.

Sohoni, P. and Sumpter, J. P. 1998. Several environmental oestrogens are also anti-androgens. Journal of Endocrinology 158, p327-339.

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 estrogens: An update on estrogenic environmental pollutants. Environ. Health Persp. 103(Suppl. 7): 113-122.


URL: http://website.lineone.net/~mwarhurst/phthalates.html