Overview of the European Risk Assessment on EDTA - ACS Publications

Chapter 20

Overview of the European Risk Assessment on EDTA Otto J. Grundler, Arnold T. M. van der Steen, and Joel Wilmot

Downloaded by CORNELL UNIV on July 23, 2016 | http://pubs.acs.org Publication Date: July 21, 2005 | doi: 10.1021/bk-2005-0910.ch020

E A C , European Aminocarboxylates Committee, 4 Avenue van Nieuwenhuyse, B-1160 Brussels, Belgium (mailto:[email protected] http://eac.ceflc.org)

EDTA has been elected by the European authorities as part of the priority substances for extensive evaluation. Consequently the German Rapporteur drafted a comprehensive and detailed Risk Assessment Report that was completed in 2003. Their conclusions show that EDTA has a low toxicity profile for both human health and environment, that there is no risk for human health and that risks for the environment are limited to some local extreme cases of high emissions to small surface waters.

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© 2005 American Chemical Society Nowack and VanBriesen; Biogeochemistry of Chelating Agents ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

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EDTA is a well-known chelating agent used to control the effect of metals in chemical processes for more than 50 years. Due to its excellent chelating performance it is used in many applications. It improves the efficiency of several industrial processes from pulp bleaching to the cleaning of dairies. It also improves the quality of food and many other product formulations and is able to increase the quality and yield of crops. In the late 1980's the environmental impact of EDTA was scrutinized in Europe because of its widespread presence in the aqueous environment and its alleged role in the solubilization of heavy metals. Presumably due to these concerns, EDTA and NaÊDTA were chosen as priority substances for extensive evaluation and control of possible risks under European Regulation 793/93. The German authorities, BAuA (Federal Institute for Occupational Safety and Health), prepared a comprehensive risk assessment report on these substances (1, 2). More than 350 studies availablefromthe open literature, scientific institutions, authorities and industry were evaluated by the authorities and the final Risk Assessment Report includes a critical review and discussion of about 250 validated references. The technical experts of the E U Member States endorsed the conclusions in 2003. The European risk assessment process follows the instructions described in detail in the extensive Technical Guidance Document (TGD) of the European Union. Both TGD and Risk Assessment Reports are available to the public on the site of the European Chemicals Bureau (3).

Conclusions of the European Risk Assessment

Human health The risk for human health is determined by comparing the expected exposures to man (exposure assessment) with available data on toxicity and critical concentrations (effect assessment). EDTA has a relatively low toxicity and the estimated (reasonable worst-case) exposure levels are below the acceptable limits. EDTA and its tetrasodium salt are not considered to be mutagenic for humans and there is no carcinogenic potential. Furthermore there are no product classification and labeling requirements for carcinogenic, mutagenic, reproductive (CMR) or sensitizing effects as approved by the E U Classification and Labelling Committee. The member state experts of the European Union came to the following conclusions in relation to human health:

Nowack and VanBriesen; Biogeochemistry of Chelating Agents ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

338 • • •

No concern for consumers in any application No concern to workers No concern to the public who may be exposed via the environment

These conclusions are in line with the conclusions of the World Health Organization (WHO) on the quality standard of600 μφ for EDTA in drinking water (4) and with several approvals for the use of EDTA as food additive in the USA (5) and Europe (6). EDTA has been successfully used in food for many years.


Environment Due to its relatively low toxicity and physical properties there is no concern of possible EDTA emissions into the atmosphere. Also a risk to terrestrial organisms is not being expected. The potential risk for the aqueous environment is evaluated by comparing the predicted no-effect concentration (PNEC) with predicted environmental concentrations (PEC's) as a result of the emissions from the various application areas. Potential risk for the aqueous environment is indicated when the PEC/PNEC ratio for a certain emission scenario is > 1. The PNEC is derivedfromecotoxicity test results on various water species in combination with a safety factor that compensates for possible uncertainties in the effect assessment. The PNEC for EDTA is derivedfrom3 long-term toxicity tests on fish, daphnia and algae in combination with a safety factor of 10. The low aquatic toxicity is expressed by the relatively high PNEC of 2.2 mg/1 for EDTA in the aqueous environment. In addition after the evaluation of a large number of studies it is concluded that there is no risk to the aqueous environment due to the influence of EDTA on the mobility of heavy metals, eutrophication and nutrient deficiency. EDTA has no potential for bioaccumulation and therefore biomagnification via the food chain is not expected either. It is well known that EDTA is not readily biodegradable. However several recent studies demonstrated that EDTA is effectively biodegraded under slightly alkaline conditions and that EDTA can be readily eliminated in wastewater treatment facilities when operated at slightly alkaline conditions. Removal rates of 90% or more have been established. Biodégradation of EDTA in the aqueous environment depends on concentration, pH and the species of complexed ions. EDTA is also eliminatedfromthe aqueous environment by photochemical degradation of some of its metal complexes. Primarily the ferric complex breaks down upon the exposure to sunlight in natural aquatic environments. Biodegradable and non-toxic metabolites have been detected in the surface waters as a result of the degradation of EDTA. EDTA and its metabolites are not


339 expected to be persistent in the aqueous environment. For the purpose of risk assessment a worst-case assumption of no biodégradation was used. Though a simple classification of'readily biodegradable' and 'persistent* chelating agents is not possible due to the influence of metal ions, pH and concentration on the biodégradation of complexing agents in general. Therefore we recommend that EDTA is to be considered as 'inherently biodegradable'. Also the European Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) indicated in their officiai opinion on the risk assessment report on EDTA (7) that the assumption of no biodégradation (persistent) should be taken as conservative worst case.


Environmental risks The detailed sections of the Risk Assessment Report clearly indicate that the risk foT the local aqueous environment is limited to a restricted number of 'extreme cases' that may appear in relatively small surface waters near effluent release points of large sites with no effective EDTA removal. The extensive monitoring data available for EDTA indicate lower concentrations man expected from the applied 'worst-case* exposure scenarios in the Risk Assessment Report. On the basis of the 'worst-case exposure scenarios' the risk assessment report indicates 4 areas where EDTA may pose a risk for aquatic organisms in the local aqueous environment; • Industrial cleaning in large dairy and beverage sites • Pulp and paper bleaching • Circuit board production • Recovery of EDTA containing (photographic) waste The Risk Assessment Report concludes that appropriate risk reduction measures should be considered to reduce any potential risk (concentrations >2.2 mg/1) for the local aqueous environment. We recommend to use the experience of countries like Sweden where local measures have been taken for more than 20 years. Permitting has lead to substantial emission reductions, proving it to be an efficient tool in managing any possible local risks of EDTA.

Details on the Human health section Justification for cross-reading from different EDTA compounds In general, edetic acid and tetrasodium EDTA show similar properties and exposure pattern. However, with respect to acute toxic and local effects both substances behave differently. Thus, the hazard effects of the two substances have been evaluated separately only for the endpoints acute toxicity and irritation. For systemic effects any conclusions on H 4 E D T A or NaÊDTA have been derived from consideration of the overall available database due to the dissociation of these compounds under physiological conditions (1,2).


340 Risk characterization Specific chapters on workers, consumers and men indirectly exposed via the environment are discussed. No risks have been identified in any of these categories. In detail the following effect assessment has been discussed. As mentioned before, H4EDTA and NaÊDTA show different patterns of irritancy and acute toxicity.


Irritation The substance has shown weak irritant properties on rabbit skin but irritations to the rabbit eye. H4EDTA is thus considered to be irritating to the eyes. N a ^ D T A may result in serious damage to the eye. However workers are protected by using adequate equipment and consumer products contains only very low levels of EDTA. Therefore no risk for irritating effects are to be considered for both consumers and workers.

Acute toxicity As no valid data on inhalation toxicity are available, assessments are based on oral data. In summary for inhalation, dermal and oral exposure, tests have shown no concern for either workers or consumers.

Sensitization Based on the intensive use in industry and consumer products for many decades where no significant problems on skin sensitization were reported, the substance is claimed to be non-sensitizing to humans. This was supported by mandatory testing in guinea pigs. In the absence of valid indications EDTA is not considered to be a respiratory sensitizer.

Repeated dose toxicity In different studies after oral and dermal applications, EDTA was evaluated to be of no concern. Exposure of children via use of cleansers for tooth brackets has been concluded to be of no concern.


341 Mutagenicity Bacterial mutation tests are negative, but mutations and D N A damage were found in mouse lymphoma cells after exposure to very high concentrations. For somatic cells in mice (bone marrow cells) negative results with respect to the endpoints micronuclei, aneuploidy and sister chromatid exchanges were described. In germ line cells negative results were obtained for induction of structural chromosomal aberrations in spermatogonia, for induction of aneuploidy in primary and secondary spermatocytes, and also for induction of dominant lethals. A positive result was obtained in a micronucleus test with spermatids, indicating that aneugenic effects may be induced in specific phases of spermatogenesis (late spermacytoge-nesis). The effect was bound to the use of an extremely high dose in the L D range. Altogether, EDTA and its sodium salts have a low mutagenic potential at extremely high doses. On the basis of the various negative findings and the assumption of a threshold mode-of action for aneugens, it can be concluded that EDTA and its sodium salts are not mutagenic forman(l,2).


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Carcinogenicity A bioassay of Na EDTA for possible carcinogenicity was conducted by administrating of test material in the diet to Fischer 344 rats and B6C3F1 mice. The studies did not report spécifie data on kidney toxicity in either species. 3

Although a variety of tumors occurred among test and control animals of both species, no tumors were related to treatment. Thus, there is no concern on a carcinogenic potential of EDTA (1,2).

Fertility Based on a multigeneration study on rats, the substance was concluded of no concern to affect the reproductive performance.

Developmental toxicity Fetotoxic and teratogenic effects occurred in rats at exposure levels of around 1000 mg/kg bw/d, EDTA is considered of no concern with regard to fetotoxic and teratogenic effects for humans.


342 Details on the Environment section

Environmental exposure


EDTA is mainly used as a complexing agent for industrial purposes. We describe some details from the extensive European Risk Assessment Report and give the PECs only for the uses identified to be of concern. According to the TGD (3) the predicted environmental concentration (PEC) near emission sources is estimated from the daily consumption of EDTA in its various applications. The concentration in the effluent is calculated from the estimated emission into a waste water treatment plant with a hypothetical effluent flow of 2000 m /hr. Subsequently the PEC is estimated from the effluent concentration assuming a hypothetical dilution factor of 1 to 10 upon release into the local surface waters and taken into account the estimated regional background concentration of EDTA. 3

The Risk Assessment Reports show a disagreement between the calculated PECs and measured EDTA concentrations in the environment. Extensive monitoring suggests actual EDTA concentrations in the aqueous environment to be lower than the P E C s estimated by the very conservative worst-case assumptions of the TGD (3). For instance extensive monitoring demonstrated that the concentrations of EDTA in large rivers were far below the presented PECregional of 95 μg/l. In addition monitored effluent concentrations presented for many application areas are always below the effluent concentrations used for the PEC determinations.

Industrial detergents EDTA is used to prevent precipitation of calcium, magnesium and heavy metals. It has various uses within the industrial and institutional detergents market. The main application area is the dairy and beverage industry. Only one of the possible scenarios with a high consumption of 10 t/a in combination with no effective EDTA removal in the wastewater treatment plants leads to a PEClocal of 2.6 mg/1. Other scenarios with less consumption and/or effective elimination in wastewater treatment plant lead to no concern.

Photochemicals In photo industry EDTA is mainly applied in the bleachflx process which is a combination of bleaching and fixing. The exposure scenario represents a large photofmisher, for which a PEClocal of 0.57 mg/1 is calculated. Wastes from photo industry are collected by special disposal companies. Bath residues are either incinerated or evaporated and deposited. Some monitoring


343 data demonstrated the presence of EDTA in the waste water at their disposal sites. TGD (3) default values result in an estimated worst-case PEClocal of 2.4 mg/1.

Pulp and paper


EDTA is used to chelate metal ions during the chlorine free bleaching process applied by paper mills. EDTA is not fixed onto the paper and is thus emitted into the sewage. Two scenarios have been used. A removal factor of 90% has been chosen for sites reflecting the best available techniques. The monitoring data for effluents of such mills give a PEClocal of 0.5 mg/1. Monitoring data from Swedish and Finnish sites (representing the majority of the European market) reveal that a PEClocal of 4.1 mg/1 resulted from the worst case scenario is not reached for any site. Therefore, this value is not used in the risk characterization. Instead, the highest estimated local concentration at a mill without an effective EDTA removal (leading to a PEClocal of 2.6 mg/1) is considered as ''worst case (1,2).

Textile industry EDTA is used in textile finishing to produce easy care fabrics, to support oxidative bleaching and to prevent catalytical damages of the fibers.

Metal plating EDTA is used for the production of printed circuit boards. EDTA is mainly used in electroless copper plating, when copper is deposited on the board by catalytic reduction of complexed copper compounds. The exposure scenario, based on the average EDTA consumption of one site and TGD default values for the dilution model, results in a PEClocal of 12 mg/1 (1,2).

Water treatment Only a limited volume is yearly used in Europe for this purpose and it is considered to be widespread with no high local exposure.


344 Polymer and rubber production EDTA is used in the production of Styrene Butadiene Elastomers (SBR) which are mainly manufactured by emulsion polymerization.

Oil production EDTA is used for well cleaning processes at oil platforms. A very high dilution factor leads to no concern.


Fuel gas cleaning In Europe there are no emissions into the waste water from this use.

Disposal (Waste recovery) Some monitoring data indicate that EDTA is released into the waste water at waste recovery sites. Results from photochemicals recovery were used as default value with a PEClocal of 2.4 mg/1.

Household sewage Household detergents, cosmetics, pharmaceuticals and food are using EDTA for complexing of trace metals. The diffuse emissions of these EDTA applications in products are not a risk for the aqueous environment

Effects assessment According to the TGD the predicted no-effect concentration (PNEC) should be determined from the no-effect level of a long-term test on the most sensitive species and an extra assessment factor of 10 (3). For EDTA the PNEC is determined from the no-effect concentrations of 3 longterm eco-toxicity tests on Fish, Daphnia and Algae. This resulted in a PNEC of 2.2 mg/1 for EDTA in the aqueous environment derived from the no-effect level of 22 mg/1 from a 21-d study with Daphnia magna (1,2). Based on environmental behaviour properties, EDTA was estimated not to be of concern for sediment, atmosphere and terrestrial compartment and the food chain. No formal PNEC was established for these compartments because of lack of appropriate studies (8).



345 The influence of EDTA on heavy metals in sediments and surface waters has been investigated in a large number of studies. EDTA has the tendency to prevent the adsorption of recently emitted heavy metals to sediments and suspended solids and to remobilize heavy metals from highly loaded sediments. Because of the complexity of the EDTA-heavy metals interactions it is not possible to present a no-effect level for metal remobilization by EDTA. The concentration of solubilized heavy metals in the aqueous phase is affected much more by natural causes -such as pH, precipitating anions and high molecular humic and fulvic acids- than by trace amounts of EDTA. In wastewater from a German municipal wastewater treatment plant and in surface water from a Spanish river it was demonstrated that the complexation of Zn, Cd and Cu was mainly determined by organic substances of high molecular weight like humic and fulvic acids and that the contribution of EDTA was limited to a few percent only. The Risk Assessment Report concludes that significant remobilization can only occur in extreme cases of high local concentrations. (1,2) The decrease of the toxicity of heavy metals by the influence of EDTA has been demonstrated in various studies. Complexation with EDTA decreased the toxicity of heavy metals to Daphnia by a factor of 17 to 1700 (1,2)

Risk characterization

Aquatic compartment The risk assessment for aquatic organisms resulted in a PNECaqua of 2.2 mg/1. A need for limiting risks has been identified in some extreme cases where the PEClocalis>2.2mg/l: the use of EDTA in industrial detergents by large sites within dairy and beverage industry, where no effective waste water treatment is applied, paper mills where no effective waste water treatment is applied, metal plating (circuit board production), releases at waste recovery sites. Risk reduction measures already in place are to be taken into account. Influence on the distribution of heavy metals: Significant remobilization by EDTA can only occur in extreme cases where local high concentrations of EDTA can be found, for example when large point sources are emitted into small rivers. At high concentrations, EDTA could prevent the adsorption of heavy metals to sediments and could remobilize metals from highly loaded sediments. Both effects lead to increased heavy metal concentrations in the water phase. Simultaneously the sediment is deloaded. At


346 the same time EDTA complexes of heavy metals are less toxic than uncomplexed metals. Considering all these facts the overall effect for the aquatic environment will be limited and a risk for the aquatic environment due to the influence of EDTA on the mobility of heavy metals is not expected.

Atmosphere


EDTA is emitted into the atmosphere as dust during production. However because of the relative low toxicity of EDTA, a risk to the environment is not expected.

Terrestrial compartment No effect tests on terrestrial organisms are available. Therefore the risk characterization has been based on calculated pore water concentrations. No risk to terrestrial organisms was expected.

Non compartment specific effects relevant to thefood chain As there is no bioaccumulation, a biomagnification via the food chain is not expected.

References 1.

German Federal Institute for Occupational Safety and Health Notification Unit, Risk Assessment of Edetic acid (EDTA) - CAS # 60-00-4 (Draft of 15 December 2003) 2. German Federal Institute for Occupational Safety and Health Notification Unit, Risk Assessment of Tetrasodium ethylenediaminetetraacetate (Na EDTA) - CAS # 64-02-8 (Draft of 15 December 2003) 3. The European Chemicals Bureau (ECB), Technical Guidance Document and Risk Assessment Reports, http://ecb.jrc.it/existing-chemicals/ 4. World Health Organization, Guidelines for Drinking-water Quality, Second edition, Addendum to Volume 2 : Health Criteria and other Supporting Information, 1998, pages 97-107, http://www.who.int/water_sanitation_health/dwq/en/2edaddvol2a.pdf 5. Title 21 - Food and drugs, Chapter I - Food and Drugs Administration, Department of Health and Human Services (Continued), part 172 - Food Additives permitted for Direct Addition to Food for Human Consumption 4


347 6.

European Parliament and Councel Directive 95/2/EC of 20 Februari 1995 on food additives other than colours and sweeteners, Official Journal L061, 18/03/1995, pages 1-40 7. German Federal Institute for Occupational Safety and Health Notification Unit, Summary Risk Assessment of Edetic acid (EDTA) - CAS # 60-00-4 (Draft of 15 December 2003) 8. Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE), Opinion on the results of the Risk Assessment of Ethylenediamine Tetraacetate (EDTA), Environmental part, Adopted by the CSTEE during the 39 plenary meeting of 10 September 2003, http://europa.eu.int/comm/health/ph_risk/committees/sct/sct_opinions_en.ht m 9. German Federal Institute for Occupational Safety and Health Notification Unit, SIDS Initial Assessment Profile for EDTA, December 2003 Downloaded by CORNELL UNIV on July 23, 2016 | http://pubs.acs.org Publication Date: July 21, 2005 | doi: 10.1021/bk-2005-0910.ch020

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Overview of the European Risk Assessment on EDTA - ACS Publications

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