Plasticisers

Di(2-ethylhexyl) phthalate (DEHP); Di(2-ethylhexyl) adipate (DEHA) (endorsed 1996)

Guideline

Di(2-ethylhexyl) phthalate: Based on health considerations, concentrations in drinking water should not exceed 0.01 mg/L.

Di(2-ethylhexyl) adipate: The data are inadequate to determine a guideline value.

General description

DEHP and DEHA are commonly used plasticisers in flexible polyvinyl chloride products. They may be present in drinking water that has been in contact with these products for long periods of time, or as the result of industrial spills. Overseas studies have detected DEHP in drinking water on a few occasions at concentrations from 0.00005 mg/L (50 ng/L) to 0.01 mg/L. DEHA has been detected at concentrations between 0.000001 mg/L (1 ng/L) to 0.0001 mg/L (100 ng/L) in treated drinking water.

DEHP is the most widely used plasticiser. It is also used as a replacement for polychlorinated biphenyls (PCBs) in electrical capacitors. DEHA is used as a lubricant and in hydraulic fluids. Exposure to DEHP and DEHA is widespread because of the broad range of products using these plasticisers. Food is the major source of exposure, and it has been estimated that adult daily intake of DEHP and DEHA, as a result of consumption of food in contact with plastic products, is 0.2 mg to 16 mg.

People receiving kidney dialysis treatment may be exposed to much higher amounts of these plasticisers. In the United States it has been estimated that each dialysis patient could be receiving up to 90 mg of DEHP per treatment.

Typical values in Australian drinking water

No data are available on DEHP or DEHA concentrations in Australian drinking waters. It is unlikely that concentrations would exceed those reported overseas.

Treatment of drinking water

There are no published reports on methods for the removal of DEHP or DEHA from drinking water.

Measurement

Measurement can be undertaken using a liquid extraction procedure (USEPA Draft Method 506 1990). The water sample is extracted with a ternary solvent consisting of methylene chloride, hexane and ethyl acetate. The extract is concentrated and analysed by gas chromatography with photoionization detection. The limit of determination is lower than 0.01 mg/L.

Health considerations

In animals, DEHP and DEHA are efficiently absorbed from the gastrointestinal tract, although marked differences in absorption are seen between species. Metabolism also differs markedly between species. Highest concentrations of metabolites are seen in the liver and adipose tissue.

An extensive review and summary of the human and animal toxicity data for DEHP is available (IPCS 1992).

Human volunteers fed up to 10 g of DEHP have experienced mild gastric disturbances, which occurred only at the highest dose. Dialysis patients receiving 150 mg per week intravenously showed no liver changes after one month, but had higher peroxisome numbers after a year. No data exist on the effects of ingested DEHA in humans.

Exposure to DEHP and DEHA can result in a significant increase in peroxisome proliferation in the liver cells of rats. An increase in peroxisome proliferation has been linked to the development of liver tumours in rodents. Humans are regarded as being less sensitive to chemically induced peroxisomal proliferation than rodents.

Long-term gavage (measured force-feeding) studies in rats using DEHP have reported that doses of 100 mg/kg body weight increased the activity of peroxisomal-associated enzymes, with higher doses resulting in depression of growth and enlargement of the liver and kidneys. Very high doses resulted in increased incidence of liver tumours. Short-term studies have reported increases in liver peroxisomal activity at lower doses (from 25 mg/kg body weight per day).

DEHP adversely affects reproduction in mice at 140 mg/kg body weight per day, and it is teratogenic and fetotoxic in mice with a no-effect level of 35 mg/kg body weight per day.

A short-term study using DEHA in rats and mice reported peroxisomal proliferation with a no-effect level of 100 mg/kg body weight per day. Longer-term studies are available, but have used much higher doses. DEHA adversely affects reproduction in rats at doses from 128 mg/kg body weight per day.

Neither DEHP nor DEHA exhibited mutagenic activity when applied to bacteria or to mammalian cells.

The International Agency for Research on Cancer has concluded that DEHA is not classifiable as to its carcinogenicity to humans (Group 3, no adequate evidence in humans and limited evidence in animals) and that DEHP is possibly carcinogenic to humans (Group 2B, no adequate evidence in humans but sufficient evidence in animals) (IARC 1982).

Derivation of the health-based guideline

The guideline values were determined as follows:

i) DEHP

$$\text{ 0.01 mg/L } = \dfrac{\text{ 25 mg/kg body weight per day x 70 kg x 0.01 }}{\text{ 2 L/day x 1000 }}$$

where:

• 25 mg/kg body weight per day is the lowest effect level based on a 14-day study using rats and hamsters (IPCS 1992). Although longer-term studies are available, they report no-effect levels at higher doses.

• 70 kg is the average weight of an adult.

• 0.01 is the proportion of total daily intake attributable to the consumption of water. Sufficient data are available to indicate that food is by far the major source of exposure, and that drinking water contributes approximately 1% of total daily intake.

• 2 L/day is the average amount of water consumed by an adult.

• 1000 is the safety factor in using the results of an animal study as a basis for human exposure (10 for interspecies variations, 10 for intraspecies variations and 10 because effects were observed at the lowest dose).

An additional safety factor for carcinogenic effects was not applied, as rats are by far the most sensitive species with respect to the sensitive end-point of peroxisomal proliferation.

The World Health Organization (WHO) guideline value of 0.008 mg/L was based on an adult body weight of 60 kg. The difference in guideline values is not significant.

ii) DEHA

The WHO has calculated a guideline value of 0.08 mg/L for DEHA based on a short-term developmental toxicity study (ICI 1988). The data are not considered to be adequate to determine an Australian guideline value.

References

IARC (International Agency for Research on Cancer) (1982). IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans: Some industrial chemicals and dyestuffs. World Health Organization, IARC, 29.

ICI (1988). Di(2-ethylhexyl)adipate: teratogenicity study in the rat. ICI Report No. CTL/P/2119.

IPCS (International Programme on Chemical Safety) (1992). Diethylhexyl phthalate. Environmental Health Criteria, 131. World Health Organization, IPCS.

USEPA Draft Method 506 (1990). Determination of phthalate and adipate esters in drinking water by liquid–liquid extraction or liquid–solid extraction and gas chromatography with photoionization detection. United States Environmental Protection Agency, Environmental Monitoring and Support Laboratory (EMSL), Cincinnati, Ohio.