Diethylhexyl phthalate
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INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 131
DIETHYLHEXYL PHTHALATE
This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization.
Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization
First draft prepared by Dr P. Lundberg, Dr. J. Hogberg, and Dr P. Garberg, National Institute of Occupational Health, Sweden, Dr I. Lundberg, Karolinska
Hospital, Sweden, and Dr S. Dobson and Mr. P. Howe, Institute of Terrestrial Ecology, United Kingdom
World Health Orgnization Geneva, 1992
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coordination of laboratory testing and epidemiological studies, and promotion of research on the mechanisms of the biological action of chemicals.
WHO Library Cataloguing in Publication Data
Diethylhexyl phthalate.
(Environmental health criteria ; 131)
1.Diethylhexyl phthalate - adverse effects 2.Diethylhexyl phthalate - toxicity 3.Environmental exposure I.Series ISBN 92 4 157131 4 (NLM Classification: QV 612) ISSN 0250-863X
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR DIETHYLHEXYL PHTHALATE 1. SUMMARY
1.1 Identity, physical and chemical properties, and analytical methods
1.2 Sources of human and environmental exposure 1.3 Environmental transport, distribution, and transformation
1.4 Environmental levels and human exposure 1.5 Kinetics and metabolism
1.6 Effects on laboratory mammals and in vitro test systems
1.7 Effects on humans
1.8 Effects on other organisms in the laboratory and field
1.9 Evaluation
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS
2.1 Identity
2.2 Physical and chemical properties
2.3 Conversion factors 2.4 Analytical methods
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 3.1 Natural occurrence
3.2 Anthropogenic sources 3.2.1 Production levels 3.2.2 Uses
3.2.3 Disposal of plasticized products 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION,
AND TRANSFORMATION
4.1 Environmental transport and distribution 4.1.1 Transport in air
4.1.2 Transport in soil and sediment 4.1.3 Transport in water
4.1.4 Transport between media 4.2 Biotransformation
4.2.1 Abiotic degradation 4.2.2 Biodegradation
4.2.2.1 Aerobic degradation 4.2.2.2 Anaerobic degradation 4.2.3 Bioaccumulation
4.2.3.1 Model ecosystems 4.2.3.2 Aquatic invertebrates 4.2.3.3 Fish
4.2.3.4 Amphibians 4.2.3.5 Plants 4.2.3.6 Birds 5. ENVIRONMENTAL LEVELS AND EXPOSURE 5.1 Environmental levels
5.1.1 Air
5.1.2 Precipitation 5.1.3 Water
5.1.4 Sediment 5.1.5 Soil 5.1.6 Food
5.1.7 Aquatic organisms 5.1.8 Terrestrial organisms 5.2 General population exposure
5.3 Occupational exposure during manufacture, formulation or use
6. KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS 6.1 Absorption
6.1.1 Inhalation 6.1.2 Dermal 6.1.3 Oral
6.1.4 Intraperitoneal 6.2 Distribution
6.3 Metabolism
6.4 Elimination and excretion 6.5 Retention and turnover
6.5.1 Half-life and body burden 6.5.2 Indicator media
7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS
7.1 Single exposure 7.2 Short-term exposure 7.3 Long-term exposure
7.4 Skin and eye irritation; sensitization
7.5 Reproduction, embryotoxicity, and teratogenicity 7.5.1 Reproduction
7.5.2 Embryotoxicity and teratogenicity 7.6 Mutagenicity and related end-points
7.6.1 Mutation
7.6.1.1 Bacteria 7.6.1.2 Fungi
7.6.1.3 Mammalian cells 7.6.1.4 Drosophila 7.6.2 DNA damage
7.6.3 DNA binding
7.6.4 Chromosomal effects 7.6.5 Cell transformation 7.6.6 In vivo effects 7.7 Carcinogenicity
7.8 Special studies
7.9 Mechanisms of hepatotoxicity 8. EFFECTS ON HUMANS
8.1 General population exposure 8.2 Occupational exposure
9. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD 9.1 Toxicity to microorganisms
9.2 Toxicity to aquatic organisms 9.2.1 Invertebrates
9.2.2 Fish
9.2.3 Amphibians
9.3 Toxicity to terrestrial organisms 9.3.1 Plants
9.3.2 Earthworms 9.3.3 Insects 9.3.4 Birds
10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 10.1 Evaluation of human health risks
10.1.1 Exposure levels 10.1.2 Toxic effects 10.1.3 Conclusion
10.2 Evaluation of effects on the environment 10.2.1 Exposure levels
10.2.2 Toxic effects 10.2.3 Conclusion
11. RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH AND THE ENVIRONMENT
12. FURTHER RESEARCH
13. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES REFERENCES
RESUME RESUMEN
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR DIETHYLHEXYL PHTHALATE Members
Dr D. Anderson, British Industrial Biological Research Association, Carshalton, Surrey, United Kingdom
Dr R. Cattley, Department of Experimental Pathology and Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA
Dr U. Chantharaksri, Department of Pharmacology, Mahidol University, Bangkok, Thailand
Dr S.D. Gangolli, British Industrial Biological Research Association, Carshalton, Surrey, United Kingdom
Dr J. Högberg, Department of Toxicology, National Institute of Occupational Health, Solna, Sweden
Mr P. Howe, Institute of Terrestrial Ecology, Monks Wood Experimental Station, Abbots Ripton, Huntingdon, United Kingdom
Dr F. Matsumura, Toxic Substances Program, Department of Environmental Toxicology, University of California, Davis, California, USA
(Chairman)
Dr S. Oishi, Department of Toxicology, Metropolitan Research Laboratory of Public Health, Tokyo, Japan
Dr C.-N. Ong, Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore (Joint
Rapporteur)
Professor G. Pliss, Laboratory for Chemical Carcinogenic Agents, N.N.
Petrov Research Institute of Oncology, Leningrad, USSR
Professor Y.-L. Wang, Department of Occupational Health, School of Public Health, Shanghai Medical University, Shanghai, China
Mr G. Welter, Federal Environmental Protection Agency, Berlin, Germany Representatives of other intergovernmental organizations
Dr M. De Smedt, Commission of the European Communities, Luxembourg Representatives of non-governmental organizations
Dr C. Elcombe, European Chemical Industry Ecology and Toxicology Centre, Brussels, Belgium
Dr B. Lake, Conseil Européen des Fédérations de l'Industrie chimique (CEFIC), Brussels, Belgium
Secretariat
Dr B.-H. Chen, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (Secretary)
Dr P. Lundberg, Department of Toxicology, National Institute of Occupational Health, Solna, Sweden (Joint Rapporteur)
Dr D. McGregor, International Agency for Research on Cancer, World Health Organization, Lyon, France
NOTE TO READERS OF THE CRITERIA MONOGRAPHS
Every effort has been made to present information in the criteria monographs as accurately as possible without unduly delaying their publication. In the interest of all users of the environmental health criteria monographs, readers are kindly requested to communicate any errors that may have occurred to the Manager of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda.
* * *
A detailed data profile and a legal file can be obtained from the International Register of Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 or 7985850).
ENVIRONMENTAL HEALTH CRITERIA FOR DIETHYLHEXYL PHTHALATE
A WHO Task Group on Environmental Health Criteria for Diethylhexyl Phthalate (DEHP) met at the British Industrial Biological Research Association (BIBRA), Carshalton, Surrey, United Kingdom, from 3 to 7 June 1991. Dr S.D. Gangolli opened the meeting on behalf of BIBRA.
Dr B.-H. Chen, IPCS, welcomed the participants on behalf of the Manager, IPCS, and the three IPCS cooperating organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the draft criteria monograph and made an evaluation of the risks for human health and the environment from exposure to DEHP.
The first draft of this monograph was prepared by Dr P. Lundberg, Dr J. Högberg, and Dr P. Garberg of the National Institute of
Occupational Health, Sweden, Dr I. Lundberg of Karolinska Hospital, Sweden, and Dr S. Dobson and Mr P. Howe of the Institute of
Terrestrial Ecology, Monks Wood Experimental Station, United Kingdom.
The second draft was prepared by Dr P. Lundberg incorporating comments received following the circulation of the first draft to the IPCS Contact Points for Environmental Health Criteria monographs.
Particularly valuable comments on the draft were made by the European Chemical Industry Ecology and Toxicology Centre (ECETOC), the
International Agency for Research on Cancer (IARC), the Toxicology Division, Exxon Biomedical Sciences, and the Conseil European des Federations de L'industrie Chimique (CEFIC).
Dr B.-H. Chen and Dr P.G. Jenkins, both members of the IPCS Central Unit, were responsible for the overall scientific content and
technical editing, respectively.
The efforts of all who helped in the preparation and finalization of the document are gratefully acknowledged.
* * *
Financial support for this Task Group was provided by the United Kingdom Department of Health as part of its contributions to the IPCS.
ABBREVIATIONS
DEHP diethylhexyl phthalate DBP di- n-butyl phthalate
DiBP di-iso-butyl phthalate
ECETOC European Chemical Industry Ecology and Toxicology Centre
ECMO extracorporeal membrane oxidation HPLC high-performance liquid chromatography MEHP monoethylhexyl phthalate
NDMA N-dimethylnitrosamine NOEL no-observed-effect level PVC polyvinyl chloride
SHE Syrian hamster embryo SPF specific pathogen free UDS unscheduled DNA synthesis
US ATSDR US Agency for Toxic Substances and Disease Registry US FDA US Food and Drug Administration
1. SUMMARY
1.1 Identity, physical and chemical properties, and analytical methods
Di(2-ethylhexyl)phthalate (DEHP) is a benzenedicarboxylic acid ester which at room temperature is a colourless to yellow oily liquid.
Its solubility in water is low (0.3-0.4 mg/litre), and is even lower in salt water. It is miscible with most common organic solvents. The volatility of DEHP is relatively low (8.6 x 10-4 Pa).
Many sampling and analytical methods have been developed for the determination of DEHP in different media. Sensitive methods, such as gas chromatography, high-performance liquid chromatography, and mass spectrometry are being used increasingly. Analysis of low
concentrations of DEHP is complicated by contamination from plastic equipment during sampling and analysis.
1.2 Sources of human and environmental exposure
Almost all the DEHP present in the environment arises from anthropogenic sources rather than from natural ones.
The worldwide production of DEHP has been increasing during recent decades and at present amounts to about 1 x 106 tonnes per year. One third of the total production is in the USA and one third in Europe.
DEHP is the most widely used plasticizer (comprising 50% of all phthalate ester plasticizers) that softens resins. It may account for 40% (w/w) or more of the plastic. DEHP is used for making the
polyvinyl chloride (PVC) utilized in building, construction and
packaging, and for medical device components. Smaller amounts are used in industrial paints and as a dielectric fluid in condensers.
Discarded plasticized products may be disposed of either by
incineration or via dumping in a landfill site. During incineration at a low temperature, a large percentage of the DEHP may be lost to the atmosphere. The environmental fate of DEHP in landfill sites has not been well studied and no definite conclusions can be reached.
1.3 Environmental transport, distribution, and transformation
Transport in the air is the major route by which phthalates enter the environment. From the atmosphere DEHP either falls or is washed out via rainfall.
DEHP has a high octanol-water partition coefficient, so the equilibrium between water and an organic-rich soil or sediment is in
favour of the soil or sediment. It is readily adsorbed by organic soil particles.
Although the solubility of DEHP in water is low, the amount present in surface water may be higher due to adsorption onto organic particles and interaction with dissolved organic matter. It is
adsorbed particularly by small particles, and adsorption is enhanced in salt water.
Atmospheric photodegradation of DEHP is rapid, but its chemical hydrolysis in the environment is practically non-existent.
Aerobic degradation has been found to be carried out by several soil microorganisms. However, the microbial degradation of DEHP in the environment has been reported to be slow. The biodegradation pathway begins with hydrolysis to the mono-ester, which is then converted to phthalic acid. The ring-opening degradation to pyruvate and succinate and then to CO2 and H2O is similar to the metabolic pathway of
benzoic acid. The aerobic degradation is temperature dependent. Below 10 °C little degradation takes place. At higher temperatures
biodegradation proceeds in the upper layer of the soil, but it is virtually non-existent deeper down where conditions are anaerobic.
Anaerobic degradation, if it exists, is very much slower than aerobic degradation.
DEHP is highly lipophilic and moderately persistent. The degree of bioaccumulation depends on the capability of an organism to
metabolize DEHP. It has been shown to accumulate to a high degree in a variety of aquatic invertebrates, fish, and amphibians.
When DEHP was applied to plant leaves, there was little loss over a 15-day period. Uptake by plants from soil or sewage sludge was found to be low.
1.4 Environmental levels and human exposure
DEHP exists widely in the environment and is found in most samples, including air, precipitation, water, sediment, soil, and biota. Levels are generally highest in industrialized areas.
DEHP concentrations of up to 300 ng/m3 have been found in urban and polluted air. Levels of between 0.5 and 5 ng/m3 have been
reported in the air of oceanic areas, and the rainfall in these areas contained up to about 200 ng/litre. Precipitation samples from an area close to a plasticizer production plant indicated that the rate of dry deposition was 0.7 to 4.7 µg/m2 per day.
In rivers and lakes the concentration of DEHP has been found to be up to 4 µg/litre, highest levels being associated with industrial effluent discharge points. The concentration in the sea is less than 1 µg/litre, highest levels being in estuaries.
Due to its hydrophobic character, DEHP is readily absorbed to soil, sediment, and particulate matter. River sediment levels of up to 70 mg/kg (dry weight) have been reported, and these have reached 1480 mg/kg (dry weight) near discharge points.
The concentration of DEHP in biota varies from less than 1 to 7000 µg/kg. It has been found in various types of food, such as fish, shellfish, eggs, and cheese. The estimated average exposure was around 300 µg/person per day in the USA in 1974 and 20 µg/person per day in the United Kingdom in 1986.
Blood transfusions and other medical treatment using plastic
devices may lead to involuntary human exposure to DEHP. Levels from 13.4 to 91.5 mg/kg (dry weight) in lung tissue have been detected in patients.
The few data available indicate that workplace concentrations of DEHP are usually below 1 mg/m3.
1.5 Kinetics and metabolism
Available data on oral administration indicate that DEHP is hydrolysed in the gut by pancreatic lipase. The metabolites formed, i.e. mono(2-ethylhexyl)phthalate (MEHP) and 2-ethyl-hexanol, are rapidly absorbed. When 14C-labelled DEHP (2.9 mg/kg) was given
orally to rats, more than 50% was recovered in the urine or bile. The bioavailability of an oral dose of DEHP seems to be higher in young rats than in older ones.
When administered orally, DEHP is extensively hydrolysed in the gut in certain animals, e.g., rats, and is mainly distributed as monoethylhexyl phthalate (MEHP). However, hydrolysis occurs to a much lesser extent in primates and humans. MEHP binds to plasma proteins.
The liver seems to be the major organ for the metabolism of MEHP and 2-ethylhexanol. Several further metabolites have been identified, omega- and omega-1-oxidation being the major metabolic pathways. One or several of the products of omega-oxidation may be further
metabolized by ß-oxidation. Non-linear kinetics have been observed for the omega-oxidation. DEHP metabolism shows considerable species
differences; e.g., the omega-oxidation pathway is less extensive in humans than in rats.
Almost 100% of an oral dose of DEHP (2.9 mg/kg) was recovered in rat faeces and urine after a week. Bile and urine are the major
excretory pathways. In a human study, 15-25% of an oral dose
(0.45 mg/kg) of DEHP was excreted as MEHP, and oxidized metabolites constituted a major portion of the excretion products.
1.6 Effects on laboratory mammals and in vitro test systems The oral LD50 for DEHP is about 25-34 g/kg, depending on the species, but the value for MEHP is lower. In feeding studies on rats and mice, DEHP dosages greater than 3 g/kg per day caused deaths within 90 days, and a level of 0.4 g/kg per day reduced weight gain within a few days. In other studies, 6.3-12.5 g/kg diet caused a body weight reduction.
Hepatomegaly and increased relative kidney weights have been observed in treated animals in long-term studies. In one study, there were also hypertrophic cells in the anterior pituitary.
Several studies have shown testicular atrophy, evident within a few days, related to DEHP administration (dietary levels of 10-20 g DEHP/kg). Younger rats seem to be more susceptible than older ones, and rats and mice seem to be more sensitive than marmosets and hamsters. Reversibility of the atrophy has been observed. MEHP has toxic effects on Sertoli cells in vitro. DEHP, as well as MEHP, shows teratogenic properties. Malformations were observed at dietary levels of 0.5-2 g/kg in mice, and embryotoxic effects were observed at dietary levels greater than 10 g/kg.
Tests for mutagenicity and related end-points have been negative in most studies. DEHP may induce cellular transformation, and it has been shown to be carcinogenic at doses of 6 and 12 g DEHP/kg diet in rats and 3 and 6 g/kg diet in mice. There was a dose-related increase in hepatocellular tumours in both sexes of both species. The induction
of hepatic peroxisome proliferation and cell replication is strongly associated with the liver carci-nogenic effect of certain non-
genotoxic carcinogens including DEHP. However, marked differences have been observed among animal species with respect to DEHP-induced
peroxisome proliferation.
In contrast to rat hepatocytes, DEHP metabolites do not produce peroxisome proliferation in cultured human hepatocytes.
1.7 Effects on humans
Only very limited information is available on the effects of DEHP on humans. Mild gastric disturbances, but no other deleterious
effects, were reported for two subjects given 5 or 10 g DEHP.
1.8 Effects on other organisms in the laboratory and field
Most studies have yielded nominal LC50 values in acute toxicity tests that are in excess of 10 mg/litre, values which give a low toxicity rating for DEHP. However, these levels exceed the DEHP water solubility (0.3-0.4 mg/litre). One study suggested greater sensitivity of the water flea Daphnia pulex, with a nominal 48-h LC50 of 0.133 mg/litre. The only acute test with measured DEHP concentrations was on the fathead minnow and revealed a 96-h LC50 of > 0.33 mg/litre. In prolonged studies, the no-observed-effect level (NOEL) for Daphnia
magna was 72 µg/litre. For adult fish a NOEL of > 62 µg/litre was determined. An exposure of 14 µg/litre, from 12 days prior to
hatching, caused a significant increase in trout fry mortality. DEHP concentrations of between 3.7 and 11 µg/litre led to a reduction in the vertebral collagen of fish.
The survival of zebra fish fry is adversely affected by DEHP concentrations of 50 mg/kg food. Sediment concentrations of 25 mg/kg (w/w) significantly reduced microbial activity and the number of tadpoles hatching.
The acute toxicity of DEHP to algae, plants, earthworms, and birds is low.
1.9 Evaluation
DEHP causes reproductive and hepatocarcinogenic effects in rats and mice.
Testicular atrophy is the main reproductive effect in rats and mice, and young animals are more susceptible than older ones to this effect. The induction of hepatic peroxisome proliferation and cell replication are strongly associated with the liver carcinogenic effect of certain non-genotoxic carcinogens including DEHP. However, marked differences have been observed among animal species with respect to DEHP-induced peroxisome proliferation. Currently there is not
sufficient evidence to suggest that DEHP is a potential human carcinogen.
There is no documented information that DEHP presents any hazard, based on acute exposure to fish and daphnids. However, a reduction of microbial activity in sediment at environmental levels of DEHP was reported. A comparison between environmental levels and the
concentrations that produce effects in prolonged studies, especially early life-stage tests on fish and amphibians, indicates that a hazard for the environment, particularly via water and sediment, cannot be excluded. Adverse effects on organisms are likely in areas with highly contaminated water and sediments which are near to point emission
sources.
Although few relevant studies have been reported, the acute
toxicity of DEHP to algae, plants, earthworms, and birds appears to be low.
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS
2.1 Identity
Common name: di(2-ethylhexyl) phthalate
Structural formula:
Empirical formula: C24H38O4
Abbreviation: DEHP Relative molecular
mass: 390.57 Common synonyms:
1,2-benzenedicarboxylic acid bis(2-ethylhexyl) ester (CAS name);
phthalic acid bis(2-ethylhexyl) ester (IUPAC name); BEHP;
1,2-benzenedicarboxylic acid bis(ethylhexyl) ester;
bis(2-ethylhexyl) 1,2-benzenedicarboxylate; bis(2-ethyl-hexyl) ester of phthalic acid; bis(2-ethylhexyl) phthalate;
di(2-ethylhexyl) ortho-phthalate; di(ethylhexyl) phthalate;
dioctyl phthalate; DOP; ethylhexyl phthalate; 2-ethylhexyl phthalate; octyl phthalate; di- sec-octyl phthalate; phthalic acid dioctyl ester
Common trade names:
Bisoflex 81; Bisoflex DOP; Compound 889; DAF 68; Ergoplast FDO;
Eviplast 80; Eviplast 81; Fleximel; Flexol DOP; Goodrite GP 264;
Hatcol DOP; Kodaflex DOP; Mollan O; Nuoplaz DOP; Octoil;
Palatinol AH; Platinol DOP; Pittsburgh; PX-138; Reomol DOP;
Reomol D 79P; Sicol 150; Staflex DOP; Truflex DOP; Vestinol AH;
Vinicizer 80; Witcizer 312 (IARC, 1982; NIOSH, 1985b) CAS registry
number: 117-81-7 RTECS number: TI 035000
Di(2-ethylhexyl) phthalate (DEHP) is available in a variety of technical grades. In the USA typical product specifications are:
minimal ester content, 99.0-99.6%; maximal moisture content, 0.1%;
acidity (as acetic acid or phthalic acid), 0.007-0.01%; specific gravity, 0.980-0.985 (25 °C/25 °C); refractive index, 1.4850-1.4870 (23 °C); and minimal flash-point, 216 °C (IARC, 1982).
In western Europe, DEHP is available with the following specifications: maximal acid value, 0.06; maximal weight loss on
heating at 140 °C for 3 h, 1%; and saponification value, 284-290 mg KOH/g (IARC, 1982).
In Japan, DEHP must fulfill the following specifications: maximal acid value, 0.05; maximal weight loss on heating at 125 °C for 3 h, 0.1%; and specific gravity, 0.983-0.989 (20 °C/20 °C) (IARC, 1982).
2.2 Physical and chemical properties
DEHP is a colourless to yellow, oily liquid at room temperature and normal atmospheric pressure. The melting point is -46 °C (pour point) and the boiling point is 370 °C (at atmospheric pressure, 101.3 kPa; 236 °C at 1.33 kPa, and 231 °C at 0.67 kPa). The flash point is 425 °C (open cup) (Clayton & Clayton, 1981; IARC, 1982; SAX, 1984). At 20 °C, the density is 0.98 g/ml (Fishbein & Albro, 1972) and the
vapour pressure 8.6 x 10-4 Pa (Howard et. al., 1985). The log n- octanol-water partition coefficient is 3-5.
The solubility of uncolloidal DEHP in water is low (45 µg/litre at 20 °C) (Leyder & Boulanger, 1983). However, DEHP may form colloidal dispersions which lead to higher values for solubility (Klöpfer et al., 1982). Values of 285 µg/litre (Hollifield, 1979), 340 µg/litre (Howard et al., 1985), and 360 µg/litre (Defoe et al., 1990) have been determined at 20-25 °C. These higher values are probably more
realistic in the environment. Howard et al. (1985) determined a value of 160 µg/litre at 25 °C in salt water.
DEHP is miscible with most common organic solvents and is more soluble in blood than water. It is lipophilic and the distribution ratio in dichloromethane-Krebs bicarbonate buffer has been measured to be 1130 (Krauskopf, 1973; Clayton & Clayton, 1981; IARC, 1982; Sax, 1984; Weast et al., 1984; Sittig, 1985).
2.3 Conversion factors
1 ppm = 15.87 mg/m3 1 mg/m3 = 0.063 ppm
2.4 Analytical methods
Methods used for the analysis of di(2-ethylhexyl) phthalate in many types of samples are summarized in Table 1.
Analysis of samples with low concentrations of DEHP is complicated by the risk of contamination from plastic equipment.
Table 1. Methods for the analysis of di(2-ethylhexyl) phthalate
Sample Sample Assay Limit matrix preparation procedure detect Air collect on cellulose GC/FID range:
ester membrane filter; 2.03-1 extract disulfide) mg/m3 a 32-l sample 23 °C Air collect with impinger GC/ECD not gi (ethylene glycol); GC/MS
extract (hexane)
Marine air trap on glass-fibre filters GC/ECD 0.5 ng with foam plugs; Soxhlet
extract (petroleum ether);
concentrate extracts; clean-up on deactivated Florisil
columns
Air-borne Soxhlet extract (methanol); GC/MS not gi particulate concentrate; centrifuge matter
River water extract (hexane); filter HPLC/UV 2 ng a (normal and 224 nm reversed-phase
adsorption chromatography and gel
chromatography
Table 1 (contd).
Sample Sample Assay Limit matrix preparation procedure detect River water extract (chloroform); thin-layer 50 µg/
concentrate extract; dry by chromatography sodium sulfate treatment;
evaporate; dissolve residue (chloroform)
Industrial add hydrochloride acid; GC/MC (EI not gi and municipal extract (dichloromethane); and CI modes);
waste water clean-up by liquid with SIM chromatographic fractionation
River freeze-dry; homogenize; HPLC/UV 10 ng sediment extract (hexane; acetone; (233 nm) methanol); evaporate;
dissolve (hexane); filter
Human serum centrifuge; extract (chloroform: GC/FID 50 µg/
methanol); evaporate; dissolve GC/MS (ethyl acetate); treat with
alumina; decant; rinse;
filter; evaporate; dissolve residue (hexane-containing butyl benzyl phthalate as an internal standard)
Human plasma separation on Celite 545; GC/FID 50 ng extract (diethyl ether);
evaporate; dissolve (carbon disulfide)
Table 1 (contd).
Sample Sample Assay Limit matrix preparation procedure detect Stored blood; lyophilize; suspend; filter; GC/FID not gi whole blood wash residue; mix with distilled water; centrifuge; add silicic
acid to chloroform phase;
mix; centrifuge; decant;
evaporate; dissolve; centrifuge
Human and grind wet tissue samples GC/FID 0.3 µg animal in saline; extract homogenate (wet t tissue and or urine; dilute with 15 ng/
urine chloroform:methanol (urine Intravenous add hydrochloric acid; GC/ECD 4 µg/l solutions extract (dichloromethane);
redissolve Organic evaporate; dissolve GC/FID not gi solvents (diethyl ether) Solid immerse in chloroform: GC/FID not gi reagents methanol; filter; rinse;
evaporate
Aluminium cut into small pieces; GC/FID not gi foil; rubber immerse in chloroform:
tubing, etc. methanol; extract
Abbreviations: GC = gas chromatography; FID = flame-ionization detection; EC electron capture detection; MS = mass spectrometry; HPLC = hi performance liquid chromatography; UV = ultraviolet spectrosc EI = electron impact; CI = chemical ionization; SIM = selecte monitoring.
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
It seems likely that by far the major part of the phthalate esters present in the environment arises from human activity and not from natural sources. Some dialkyl esters may be found in coals, crude oil, and shales while others may have plant origins, but most
originate either directly or indirectly from industrial processes.
Phthalic acid has been reported to be formed during the bacterial metabolism of phenanthrene.
3.1 Natural occurrence
Phthalates have been reported in a wide variety of substances (oil, soil, plants, and animals) and over a wide geographical area.
Most occurrences have anthropogenic origins but some could be of
natural origin. The nature of the origin is further complicated by the fact that sampling techniques often lead to contamination of samples via contamination from plastic bags or bottles. Mathur (1974a)
critically reviewed this question and concluded that the possibility of the phthalic acid esters found in biological and geochemical
samples being of biosynthetic origin cannot be ruled out. Both Mathur (1974a) and Peakall (1975) cite reports where phthalates were detected yet no anthropogenic source could be found. Studies by Manandhar et al. (1979) and Pare et al. (1981) also revealed residues of phthalates in biological samples where the source seemed to be natural. Peterson & Freeman (1984) suggested that some of the phthalates found in older samples (from the 1920s and 1930s) of sediment cores from Chesapeake bay, USA, may have been of natural origin.
An ECETOC (European Chemical Industry Ecology and Toxicology Centre) task force concluded that, although knowledge of naturally produced phthalates is limited or uncertain, it is unlikely that this contribution is of significance except, possibly, in very localized areas (ECETOC, 1985).
3.2 Anthropogenic sources
3.2.1 Production levels
About 2.7 x 106 tonnes of total phthalates are produced annually, of which the non-plasticizer (dimethyl and diethyl) phthalates represent a very small fraction. Of the plasticizer phthalates, DEHP accounts for well over 50% of the tonnage, the contribution of the remaining compounds ranging from about 1% to 10%
each (ECETOC, 1985).
The production of DEHP has been increasing since it was first used commercially in 1949. During the period 1950-1954, the production in the USA was 106 x 103 tonnes, and by the period 1965-1969 the
level had risen to 650 x 103 tonnes (Peakall, 1975).
The estimated world consumption of DEHP in 1984 was 1.09 x 106 tonnes (SRI, 1985).
3.2.2 Uses
Phthalate acid esters are the most widely used plasticizers for the production of polyvinyl chloride (PVC) products (with DEHP as the plasticizer). Phthalates are used for the insulation of wires and cables, in floor tiles, weatherstripping, upholstery, garden hose, swimming pool liners, footwear and clothing. They are also used in food wrapping and containers, although in some countries this use is prohibited by law. They also have non-plasticizer uses, e.g., as pesticide carriers.
DEHP has been widely used since 1949. An important property is that it softens resins without reacting with them chemically. This has led to about 95% of DEHP production being directed towards plasticizer use, particularly in PVC products such as tubing and medical device components. It is also used as a plasticizer in cellulose ester
plastics and synthetic elastomers. The DEHP content of these products generally ranges from 20 to 40%, but for some uses it is up to 55%.
The most important non-plasticizer use of DEHP is as a dielectric fluid in capacitors.
3.2.3 Disposal of plasticized products
Most discarded plasticized products are disposed of either by incineration or via dumping in a tip/landfill site. When incinerated at high temperature the combustion of phthalates is nearly complete.
However, if combustion is uncontrolled and occurs at a low
temperature, a large percentage of the phthalates may be lost to the atmosphere. After dumping in a landfill site, phthalates may leach into the aquatic environment, but because of their high affinity for organic soil particles and their low water solubility this is not likely to be a major route into the environment. Indiscriminate
dumping is more likely to lead to volatilization of phthalates to the atmosphere rather than leaching to the aquatic environment (ECETOC, 1985).
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION 4.1 Environmental transport and distribution
The release of phthalates to the environment may occur as follows:
a) during production and distribution;
b) during the manufacture of plasticized products;
c) during the use of plasticized product;
d) after disposal.
It was concluded by ECETOC (1985) that most of the phthalates entering the environment are likely to do so by volatilization to the atmosphere, only a minor part (perhaps 10%) entering the aquatic environment by leaching.
The estimated worldwide emissions of DEHP are given in Table 2.
However, as reported by ECETOC (1985), the loss of DEHP from modern production plants is negligible.
4.1.1 Transport in air
ECETOC (1985) suggested that transport in air is the major route by which phthalates enter the environment. DEHP is volatilised to the atmosphere and then either falls as dry deposition or is "washed out"
via rainfall.
DEHP has been measured in air samples from remote sites at Enewetak Atoll in the North Pacific Ocean (Atlas & Giam, 1981), the North Atlantic (Giam et al., 1978), the Gulf of Mexico (Giam et al., 1978, 1980), and Sweden (Thurén & Larsson, 1990).
4.1.2 Transport in soil and sediment
DEHP has a high n-octanol-water partition coefficient, so the equilibrium between water and an organic-rich soil or sediment will be very much in favour of the soil or sediment. Absorbance of DEHP by soil or sediment is also enhanced by van de Waals type bonding with natural soil minerals, promoted by the presence of benzene rings and carbonyl groups, and also by the low solubility of DEHP (ECETOC, 1985).
From results with other organic substances, Wams (1987) estimated that 90% of DEHP is readily adsorbed by organic soil particles.
As can be seen from section 5.1.4, the sediment or hydrosoil tends to act as a sink for DEHP.
Table 2. Estimated worldwide emission of DEHP, based on an estimated total annual production of 4 x 106 tonnesa
Phase Emission (tonnes/year) Route Production up to 40 000 waste water Distribution 2000 sewage systems Production of PVC 32 000 air and water During use of plastics 14 000 air
6000 water After disposal:
to landfill sites up to 200 000 percolating water to waste incinerators ? air
uncontrolled burning ? air
a Adapted from Wams (1987). The values are higher than those from other sources (ECETOC, 1985)
4.1.3 Transport in water
The solubility of DEHP in water is low (0.3 mg/litre at 25 °C).
However, the amount present in surface water may be higher than the actual solubility as a result of adsorption onto organic particles
(Taylor et al., 1981) and interactions with dissolved organic matter of high relative molecular mass, such as humic and fulvic acid
(Matsuda & Schnitzer, 1971).
DEHP has been found to adsorb to suspended particulate matter fairly rapidly, in less than 2 to 3 h, especially to small particles (Al-Omran & Preston, 1987). This adsorption was more rapid in salt water than in fresh water. Taylor et al. (1981) reported that between one-half and two-thirds of the DEHP in Mississippi River water is associated with particulate matter.
By extrapolating laboratory data on the volatilization of DEHP from water under defined conditions, Klopffer et al. (1982) obtained a half-life in water of 146 days, although on purely theoretical grounds a value of only 25 days was calculated.
Using the Exposure Analysis Modeling System (EXAMS), Wolfe et al.
(1980a) calculated that at equilibrium the loss of DEHP via
volatilization from a model river, a pond, an eutrophic lake, and an oligotrophic lake would be 0%, 2.8%, 2.2% and 2.3%, respectively.
4.1.4 Transport between media
Eisenreich et al. (1981) estimated that the total annual deposition of DEHP from air into the Great Lakes, North America, varied from 3.7 tonnes (Lake Ontario) to 16 tonnes (Lake Superior).
DEHP has a high n-octanol/water partition coefficient. This means that biota living in phthalate-containing water would be
expected to have a higher phthalate level than the water itself (see section 4.2.3). However, many organisms are able to metabolize DEHP, and the concentrations found may be lower than those expected on the sole basis of partition coefficient.
During the 33-day period of a model ecosystem study, the concentration of 14C in the aquatic phase reached a peak of 31 µg/litre at the fifth day after treatment and had declined to 7.7 µg/litre by the end of the experiment. This decline was stated to be the result of the uptake of DEHP and its degradation products by the organisms in the model ecosystem (Metcalf et al., 1973).
Lokke & Bro-Rasmussen (1981) treated the leaves of Sinapsis alba with a mixture of di-iso-butyl phthalate (DiBP), di- n-butyl
phthalate (DBP), and DEHP at a rate of 2.5 µg/cm2. Only very small amounts of DEHP evaporated from the leaves during the 15-day
experiment, compared with DiBP (71%) and DBP (43%).
4.2 Biotransformation
4.2.1 Abiotic degradation
As a result of atmospheric photodegradation, the atmospheric half-life of DEHP is less than one day (ECETOC, 1985).
Chemical hydrolysis of DEHP is practically non-existent, the half-life being > 100 years in water at pH 8 and 30 °C (Wolfe et al., 1980b).
4.2.2 Biodegradation
Aerobic degradation has been found from several micro-organisms in soil, sludge, sediment, and water. Anaerobic degradation is very much slower, or possibly even non-existent.
The first step in the metabolic pathway for the biodegradation of DEHP is the hydrolysis of the diester to the monoester by esterases with low substrate specificity (Kurane et al., 1980; Taylor et al., 1981). The monoester is then converted into phthalic acid (Engelhardt et al., 1975). The ring-opening degradation to pyruvate and succinate and then to CO2 and H2O is similar to the metabolism of benzoic
acid. According to Kurane et al. (1984), this is probably why the biodegradation of phthalic esters is so widespread. It appears that mixed populations of microorganisms are the most successful at completely degrading DEHP (Engelhardt et al., 1975; Kurane et al., 1979). When pure cultures of bacteria, selectively isolated in the laboratory, are used for the biodegra-dation of phthalates,
accumulation of the breakdown products tends to occur (Keyser et al., 1976).
4.2.2.1 Aerobic degradation
Aerobic degradation of DEHP has been found with several
microorganisms, including bacteria and fungi. Overall, it appears that phthalates with short alkyl chains undergo rapid degradation, whereas those with longer chains, such as DEHP, are only 40-90% degraded after 10-35 days (ECETOC, 1985).
Graham (1973) reported that laboratory-scale activated sludge processes degraded 91% of introduced DEHP within 38 h. Saeger & Tucker (1973) demonstrated that all phthalates tested underwent complete aerobic degradation in activated sludge and river water.
Aerobic degradation of DEHP depends on temperature. Mathur (1974b) incubated a loam soil with DEHP at 4, 10, 22-25, and 32 °C, and soil respiration rates were measured after 14 weeks. Increased rates of respiration, showing that microbial degradation was taking place, were found at all temperatures. However, at 4 and 10 °C results indicated that only marginal degradation was taking place.
Johnson & Lulves (1975) incubated freshwater hydrosoil containing
14C-DEHP (1 mg/litre) under aerobic conditions, and after 14 days, 50% of the DEHP had been degraded. This was a much slower rate of degradation than that found with DBP, where 98% was degraded within 5 days. Johnson et al. (1984) studied the biodegradation of phthalic acid esters in freshwater sediment and found that the length and configuration of the alkyl phthalate diester significantly affected the primary biodegradation rate. After a 14-day incubation in aerobic sediment at 22 °C, less than 2% of the branched-chain alkyl phthalate DEHP had been degraded whereas over the same period the linear alkyl DBP showed 85% degradation. DEHP degradation was significantly greater at very high concentrations (10 mg/litre) and at temperatures above 22 °C. Neither inorganic nitrogen nor phosphorus influenced the
degradation of DEHP. Engelhardt et al. (1977) found that the fungus Penicillium lilacinum degraded approximately half of the initial amount of DEHP within 30 days, yielding the corresponding monoester, a second metabolite, which is hydroxylated in the alcohol moiety, and at least four minor metabolites. The bacterium Pseudomonas
acidovorans completely degraded DEHP at a medium concentration of 5000 mg/kg within 72 h (Kurane et al., 1977).
Saeger & Tucker (1976) found that 60% of the DEHP had undergone primary biodegradation within 5 weeks in Mississippi River water.
Rapid primary degradation was found when DEHP was added to activated sludge at the rate of 5 mg/24 h. Depending on the source of the
sludge, between 70% and 78% was degraded. To monitor whether complete biodegradation was being achieved, the authors measured CO2
evolution. Within the 14 days of incubation DEHP had essentially been completely degraded to CO2 and water under the conditions of this
test. Taylor et al. (1981) showed the presence of significant
populations of taxonomically distinct bacteria that grew on a range of phthalic acid esters, including DEHP, in the water and sediments of the Mississippi River region.
Sugatt et al. (1984) used an acclimated shake-flask
CO2-evolution test to study the biodegradation of DEHP and reported an initial breakdown of the parent compound of > 99% within the 28 days. The authors calculated a half-life of 5.25 days for the primary biodegradation of DEHP.
In surface waters, DEHP is strongly adsorbed to organic particles (Taylor et al., 1981), which tends to reduce degradation (Baughman et al., 1980).
In the upper layer of soil, biodegradation of phthalates proceeds as in surface water, but deeper down, where conditions are anaerobic, it is virtually nonexistent (Engelhardt & Wallnofer, 1978). Shanker et al. (1985) incubated garden soil containing DEHP at a concentration of 500 mg/kg. Within 20 days, 75% of the DEHP had been degraded and, after 30 days, more than 90%. Again the rate of degradation was much slower than that found for either di- n-methyl or di- n-butyl
phthalate. No degradation was detectable when sterilized soil was used.
4.2.2.2 Anaerobic degradation
Johnson & Lulves (1975) found DEHP to be completely resistant to microbial attack under anaerobic conditions. After 30 days, there was no significant loss of 14C-DEHP activity in freshwater hydrosoils overlaid with nitrogen.
Shanker et al. (1985) reported that degradation of DEHP was much slower in anaerobic soil, flooded with sterile water to reduce the oxygen tension. After a 30-day incubation, 33% of the DEHP had been degraded, compared with more than 90% in the case of aerobic soil.
O'Connor et al. (1989) studied the biodegradation of DEHP under anaerobic conditions in a medium containing municipal digester sludge over a period of 140 days. DEHP, which was the only carbon source, was added at a rate of 20, 100, and 200 mg/litre, and 100%, 69%, and 54%
of the DEHP was degraded at the three respective concentrations.
However, complete biodegradation to carbon dioxide and methane was minimal.
Ziogou et al. (1989) studied the behaviour of DEHP (0.5, 1, and 10 mg/litre) during batch anaerobic digestion of sludge over a 32-day period. No degradation of DEHP was observed during this period.
4.2.3 Bioaccumulation
DEHP is highly lipophilic, the log n-octanol-water partition coefficient being 3 to 5, and it is moderately persistent. The accumulation of DEHP is also influenced by the capability of an
organism to metabolize it. Melancon (1979) reviewed the metabolism of phthalates in aquatic organisms. Bioconcentration factors for DEHP in a variety of aquatic organisms are given in Table 3.
Table 3. Bioaccumulation of DEHP in aquatic organisms
Organism Stat/ Exposure Exposure Bioconce flowa period concentration fact (µg/litre)
Freshwater organisms
Canadian pondweed stat 24 h 10 274.8 (Elodea canadensis) stat 12 h 10 000 133.8 Snail stat 48 h 10 857.5
( Physa sp) stat 6 h 10 000e 402
Scud flowb 7 day 0.1 13 60 (Gammarus pseudolimnaeus) flow 7 day 0.1 3900
Water flea flowb 7 day 0.3 5200
(Daphnia magna) flow 7 day 0.3 420
stat 1 h 10 421d stat 12 h 10 000e 133.8 Sowbug flowb 21 day 62.3 250
(Asellus brevicaudus) Mosquito (larvae) stat 12 h 10 1320.2 (Culex pipiens stat 24 h 10 000e 1187.3 quinquefasciatus) stat 24 h 10 20.3 stat 48 h 10 000e 434.6 Midge larvae (3rd instar) flowb 7 day 0.2 408
(Chironomus plumosus) flowb 7 day 0.3 3100
flow 7 day 0.3 350
Mayfly flowb 7 day 0.1 2300
(Hexagenia bilineata) flow 7 day 0.1 575
Table 3 (contd). Organism Stat/ Exposure Exposure Bioconce flowa period concentration fact (µg/litre) Mosquito fish stat 48 h 100 265
(Gambusia affinis) stat 12 h 10 000e 129
Fathead minnow flow 14 day 1.9 45
(Pimephales promelas) flow 56 day 1.9 88
Marine organisms Eastern oyster (muscle) stat 24 h 100 11
(Crassostrea virginica) stat 24 h 500 6
Brown shrimp stat 24 h 100 10
(Penaeus aztecus) stat 24 h 500 16
Sheepshead minnow stat 24 h 100 10
(Cyprinodon variegatus) stat 24 h 500 13
a Stat = static conditions (water unchanged for the duration of the test); f (DEHP concentration in water continuously maintained, unless stated otherw
b Intermittent flow-through conditions
c Bioconcentration factor = concentration of DEHP in organism divided by con
d Bioconcentration factor calculated using a radioactive isotope (values rep radiolabelled products)
e DEHP applied directly to water 4.2.3.1 Model ecosystems
Metcalf et al. (1973) studied the uptake of 14C-labelled DEHP from water by aquatic organisms in a model ecosystem containing algae
(Oedogonium), snails ( Physa sp.), mosquito larvae (Culex pipiens quinquefasciatus), and fish ( Gambusia sp). The mosquito larvae showed the highest concentration factor and the fish the lowest.
Labelled DEHP was added to Sorghum plants and at the end of the 33- day experiment the water contained 0.34 µg DEHP per litre, the algae 18.32 mg/kg (53 890 x), the snails 7.3 mg/kg (21 480 x), the mosquito larvae 36.61 mg/kg (10 7670 x), and the fish 0.044 mg/kg (130 x).
Sodergren (1982) exposed fish, aquatic invertebrates, and plants to 14C-labelled DEHP at a concentration of 1.4 mg/litre for 27 days under static conditions. After 5 days, 1/50 of the added amount of DEHP was still present in the water, and at the end of the experiment 62% was recovered from the various surfaces (glass walls, sediment and surface microlayer). All organisms accumulated DEHP. The amphipod
Gammarus pulex, larvae of trichopterans, and the snail Planorbis corneus accumulated the DEHP to the highest degree, the
concentration factors ranging from 17 000 to 24 000. The submerged plants, Mentha aquatica and Chara chara, also showed uptake and storage of large amounts (concentration factor of 18 000). However, the fish (stickleback, Pungitius pungitius, and minnow, Phoxinus
phoxinus) did not accumulate 14C-DEHP to any great extent
(concentration factors of 300 or less). Large accumulations of DEHP occurred in organisms living and/or feeding at interfaces.
4.2.3.2 Aquatic invertebrates
Brown & Thompson (1982a) exposed Daphnia magna to nominal
14C-labelled DEHP concentrations of 3.2, 10, 32, and 100 µg/litre for 21 days and obtained bioconcentration factors of 166, 140, 261, and 268 at the four respective concentrations.
When Brown & Thompson (1982b) exposed mussels (Mytilus edulis) to labelled DEHP at concentrations of 4.1 and 42.1 µg per litre, in both cases equilibrium was reached within 14 days with a concentration factor of 2500. Exposure ceased on day 28 but the mussels were
monitored for a further 14 days. The half-life for loss of DEHP over this period was calculated to be 3.5 days.
Laughlin et al. (1978) exposed grass shrimp, during larval development, to DEHP concentrations of up to 1 mg/litre for 28 days.
DEHP was not detectable in shrimp tissues at or above a level of 2 mg/kg.
When Streufert et al. (1980) exposed midge larvae (Chironomus plumosus) to a radioactively labelled DEHP concentration of 0.2 µg/litre, the larvae accumulated DEHP to 292 times the concentration in water within 2 days. DEHP levels in the midge larvae reached a plateau after 7 days at a bioconcentration factor of 408. Some of the larvae were transferred to clean water after 4 days, by which time they had accumulated 56 µg DEHP/kg, and the half-life for loss was calculated to be 3.4 days.
After 9 weeks of exposure to sediment containing approximately
600 mg/kg, dragonfly larvae had taken up 14.7 mg DEHP per kg. This was significantly more than control larvae, which contained 2.9 mg/kg (Woin & Larsson 1987).
Hobson et al. (1984) fed penaeid shrimps on a diet containing between 40 and 50 000 mg DEHP/kg for 14 days at a rate of 40 g/kg body weight per day. Whole body residues ranged from 0.249 to 18.3 mg/kg in a dose-related manner.
4.2.3.3 Fish
Macek et al. (1979) exposed bluegill sunfish (Lepomis
macrochirus) to 14C-DEHP, both via food at a concentration of 2.8 mg/kg and via water at 5.6 µg/litre, for up to 35 days. The steady- state body burden of 14C-DEHP after exposure via food and water was 0.73 mg/kg and via water alone was 0.64 mg/kg. The authors concluded that the uptake of DEHP via the aquatic food chain was statistically indistinguishable from that due to aqueous exposure. The time required for the fish to eliminate 50% of the residue burden during depuration in uncontaminated water was < 3 days.
In a study by Karara & Hayton (1989), sheepshead minnows (Cyprinodon variegatus) were exposed to a 14C-DEHP concentrations of 60 ng/litre at temperatures ranging from 10 °C to 35 °C for a
period of between 72 h and 160 h. The amount of DEHP accumulated after 72 h was 6 times greater at 35 °C than at 10 °C, and the
bioconcentration factors increased exponentially with temperature from 45 at 10 °C to 6510 at 35 °C. Metabolic clearance also increased as a function of temperature, the maximum value being reached at a
temperature of between 29 °C and 35 °C.
Tarr et al. (1990) exposed three sizes (2.9 g, 61 g, and 440 g) of rainbow trout (Oncorhynchus mykiss) to 14C-DEHP at 20 ng/ml
under static conditions for up to 96 h at 12 °C. The body-weight- associated changes in the pharmacokinetic parameters caused the bioconcentration factor to decline from 51.5 to 1.6 as body weight increased.
When Mehrle & Mayer (1976) exposed rainbow trout (Salmo
gairdneri) eggs (12 days prior to hatching to 24 days post-hatching) to 14C-labelled DEHP at concentrations of 5, 14, and 54 µg/litre, the bioconcentration factors were 78, 113, and 42, respectively.
Mayer (1976) exposed fathead minnows (Pimephales promelas) to DEHP concentrations ranging from 1.9 to 62 µg/litre for 56 days under flow-through conditions. As the exposure concentration increased, concentration factors, measured after 56 days, decreased from 569 to 91. Equilibrium was attained after 28 days at the lowest dose and after 56 days at the highest dose. After exposure the fish were placed in uncontaminated water for 28 days, and the half-lives for loss
ranged from 6.2 days (at 2.5 µg/litre) to 18.3 days (at 62 µg/litre).
4.2.3.4 Amphibians
Larsson & Thuren (1987) exposed moorfrog eggs to sediment DEHP concentrations ranging from 10 to 800 mg/kg (fresh weight of
sediment). The eggs hatched after about 3 weeks and the tadpoles were analysed after 60 days. The DEHP was released from the sediment to the overlying water, and the losses to the water increased linearly with increasing levels in the sediment (from 0.89 to 187.4 µg/litre). DEHP accumulated in the tadpoles at concentrations ranging from 0.28 to 246.8 mg/kg wet weight, and the accumulation increased with increasing DEHP concentration, both in sediment and water.
4.2.3.5 Plants
Lokke & Bro-Rasmussen (1981) applied DEHP as a mixture that also contained DiBP and DBP at a concentration of 2.5 µg/cm2 to the
leaves of Sinapis alba. The residue level of DEHP on the leaves immediately after application was 2.7 µg/cm2. After 15 days, DEHP levels had decreased to 0.8 µg/cm2, but when the growth of the plant was taken into account, no significant loss of DEHP over this period was found. Lokke & Rasmussen (1983) also found little loss of DEHP over a 15-day period when they applied it (as a mixture with DBP) to
Achillea at a concentration of 3.5 µg/cm2 or to Sinapis at 3.1 µg/cm2. Residues ranged from 120 to 155 µg/plant, and approximately 80% of the DEHP accumulated was on the surface of the leaf.
When Schmitzer et al. (1988) grew barley from seed in soil containing 1 or 3.33 mg 14C-DEHP/kg dry soil for 7 days, only 0.61%
and 1.25%, respectively, of the applied 14C was taken up by the plants. Aranda et al. (1989) also found low accumulation of DEHP by plants grown in sewage sludge containing DEHP. Lettuce (Lactuca sativa), carrot (Daucus carota), chile pepper (Capiscum annuum), and tall fescue (Festuca arundinaca) were all grown in sludge containing 14C-DEHP levels of between 2.57 and 14.07 mg/kg.
Bioconcentration factors ranged from 0.06 to 0.53 (based on initial soil concentration and plant dry weight).
4.2.3.6 Birds
Belisle et al. (1975) fed mallard ducks (Anas platyrhynchos) on a diet containing 10 mg DEHP/kg for a period of 5 months. No DEHP was detected in fat tissue, but 0.1 and 0.15 mg/kg (wet weight) were found in breast muscle and lung tissue, respectively.
O'Shea & Stafford (1980) exposed starlings (Sturnus vulgaris) to a dietary DEHP concentration of 25 or 250 mg/kg for 30 days. One of eight birds fed 25 mg/kg contained detectable residues (1.6 mg/kg) after 30 days exposure, and five of eight birds fed 250 mg/kg
contained an average of 1.8 mg/kg. The same proportion of birds fed the higher dose still had detectable residues (an average of 1.3 mg/kg) 14 days after dosing had finished.
When Ishida et al. (1982) fed hens on a diet containing 5 or 10 g/kg for up to 230 days, DEHP was detected in all tissue monitored except the brain. Residues ranged from non-detectable to 42.5 mg/kg for most tissues. However, adipose tissue (192.7 to 899.6 mg/kg) and feathers (513.1 to 1165.2 mg/kg) accumulated the highest
concentrations. A similar pattern of uptake was observed in hens fed 2 g/kg for 25 days, although the amount of DEHP accumulated was much lower. At this dose level no accumulation had occurred in tissues other than liver and feather within 5 days.
5. ENVIRONMENTAL LEVELS AND EXPOSURE 5.1 Environmental levels
DEHP exists widely in the environment and is found in most samples, including air, precipitation, water, sediment, soil, and biota. Residues have also been detected in food and in humans.
In many cases it is not clear whether the phthalate measured in samples is naturally occurring or is exogenous. However, there seem to be clear indications that high levels of DEHP are anthropogenic in origin.
5.1.1 Air
The levels of DEHP in air have been monitored in the North Atlantic, the Gulf of Mexico, and on Enewetak Atoll in the North Pacific and found to range from not detectable to 4.1 ng/m3 (Giam et al., 1978; Giam et al., 1980; Atlas & Giam 1981). Similar levels (between 0.5 and 5 ng/m3) have been found in the Great Lakes ecosystem (Eisenreich et al., 1981) and in the Swedish atmosphere (Thurén & Larsson, 1990). The DEHP content of these samples was at least an order of magnitude lower than those found in urban areas such as New York city, where levels of up to 28.6 ng/m3 have been found (Bove et al., 1978). Based on the analysis of snow samples, Lokke &
Rasmussen (1983) calculated DEHP concentrations in air of 22 ng/m3 at Lyngby, Denmark. Levels of 29-132 ng/m3 have been found in
Antwerp, Belgium (Cautreels et al., 1977), 126 ng/m3 in polluted air in Belgium (Cautreels & Van Cauwenberghe, 1978), 300 ng/m3 in
polluted air in Canada (Thomas, 1973), and 38-790 ng/m3 in Japan in 1985 (Environment Agency of Japan, 1989).
5.1.2 Precipitation
Atlas & Giam (1981) measured levels of DEHP in rainfall at Enewetak Atoll, North Pacific, of 5.3-213 ng/litre (mean, 55
ng/litre). Eisenreich et al. (1981) reported between 4 and 10 ng/litre in precipitation falling on the Great Lakes ecosystem and Thurén &
Larsson (1990) a level of 55 ng/litre in Sweden. Goto (1979) found a range of mean rainwater concentrations of 0.65 to 3.16 µg/litre in various Japanese cities.
Lokke & Rasmussen (1983) analysed snow sampled near a plasticizer production plant 14 days after a snowfall. Levels of DEHP ranged from 0.7 to 4.7 µg/m2 per day over this period, the highest levels being within 150 m of the plant and the lowest levels at least 600 m away.
5.1.3 Water
Levels of DEHP found in water are summarized in Table 4.
Table 4. Concentrations of DEHP in water
Location Country Year Concentration Reference µg/litrea
Marine
Northern Atlantic 0.0001-0.006 Giam et al. (19 Gulf of Mexico 0.006-0.316 Giam et al. (19 Estuaries Germany ND-0.3 Weber & Ernst ( Nueces Estuary,
Texas USA 1980 0.2-0.77 Ray et al. (198 Estuaries United Kingdom 1981 0.058-0.078 Waldock (1983)
Freshwater
Various rivers Japan ND-3.1 Kodama et al. ( Various cities Japan 1974 0.1-2.19 Goto (1979) River Meuse Netherlands 1983 < 0.1-3.5 Wams (1987) River Rhine Netherlands 1983 ND-1.2 Wams (1987) River Rhine Netherlands 1982 ND-4.0 Wams (1987)
a ND = not detectable
