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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic behaviour of trisodium hydrogen ethylenediaminetetraacetate (CAS 150-38-9) has been investigated. Also for the structurally related substances disodium dihydrogen EDTA (CAS 139-33-3) and tetrasodium EDTA (CAS 64-02-8) no reliable information on the disposition and metabolism in experimental animals or humans is available. For disodium hydrogen EDTA a few poorly reported toxicokinetic experiments have been performed (Yang et al., 1964). The results of these experiments are cited in this document in the appropriate sections.

In accordance with Annex VIII, Column 1, Section 8.8.1, of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017), assessment of the toxicokinetic behaviour of trisodium hydrogen EDTA (CAS 150-38-9) is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017) and taking into account further available information on structural analogue substances.

The substance trisodium hydrogen EDTA is an organic solid at 20°C with a molecular weight of 358.2 g/mol. The water solubility and log Pow values are 201.3-212.9 g/L and -3.8 at ambient temperature, respectively. The pH value is 7.2 - 8.7. Trisodium hydrogen EDTA solution showed no evaluable vapour pressure curve in the temperature range of 126.0 to 150.9 °C. Due to this result, the vapour pressure for the temperatures 20, 25 and 50 °C was estimated to be < 7 mPa.


Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2017).


In general, molecular weights below 500 and log Pow values between -1 and 4 are favorable for absorption via the gastrointestinal (GI) tract. Water-soluble substances will readily dissolve into the gastrointestinal fluids. Absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Thus absorption of the molecule in the gastrointestinal tract can be expected to be limited.

After gavage administration of 400 mg/kg bw of the source substance disodium dihydrogen EDTA (CAS 1239 -33 -3) to weanling and adult rats roughly 90 % of the dose were recovered in feces, while only 5.3 % (adults) - 8.6 % (weanlings) were recovered in urine within 48 h. It was therefore assumed that most of the orally applied disodium dihydrogen EDTA is not absorbed (Yang, 1965). After a single gavage application of ca. 475 mg/kg bw to rats, the gastrointestinal tract was removed in intervals up to 32 h and the EDTA content analyzed. All disodium dihydrogen EDTA passed through the stomach within 12 h and 93 % of the dose was recovered in the colon after 32 h, which demonstrated a poor absorption from GI tract (Yang, 1964).

The observation of systemic toxicity following exposure by any route is an indication for substance absorption; however, this will not provide any quantitative information.

A two year feeding study with trisodium hydrogen EDTA (CAS 150-38-9) to rats revealed a NOAEL of ≥495 mg/kg/day (corresponding to 7500 ppm in the diet). In this feeding study with two dose levels, 3750 ppm and 7500 ppm (corresponding to 248 and 495 mg/kg bw/day), no substance related toxic effects were observed. The same study at the same dose levels (3750 ppm and 7500 ppm; corresponding to approximately 469 and 938 mg/kg bw/day) conducted with mice showed a NOAEL of ≥938 mg/kg bw/day. There were also no treatment related changes. Based on the results of these oral repeated dose toxicity studies with trisodium hdyrogen EDTA, no conclusion on the absorption of the test substance via the gastrointestinal tract is possible.

Overall, taking into account the physical-chemical properties of trisodium hydrogen EDTA, the oral absorption potential of the substance is anticipated to be low.


The smaller the molecule, the more easily it may be taken up. In general, a molecular weight below 100 g/mol favors dermal absorption, above 500 g/mol the molecule may be too large (ECHA, 2017). As the molecular weight of trisodium hydrogen EDTA is 358.2 g/mol, dermal absorption of the molecule might be possible. However, as the test substance is a solid, hindered dermal absorption has to be considered as dry particulates first have to dissolve into the surface moisture of the skin before uptake via the skin is possible (ECHA, 2017).

Moreover, a substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. However, if water solubility is above 10,000 mg/L and the log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum (ECHA, 2017). Thus dermal uptake of trisodium hydrogen EDTA will be low.

The dermal permeability coefficient (Kp) can be calculated from log Pow and molecular weight (MW) applying the following equation described in US EPA (2014):

log Kp (cm/h) = -2.80 + 0.66 log Pow – 0.0056 MW

The calculated Kp for trisodium hydrogen  EDTA is 4.56 E-08 cm/h and a dermal flux rate of 3.44 E-05 mg/cm2 per h was calculated indicating a very low dermal absorption potential for trisodium hydrogen EDTA  (please refer to Table 1).

Table 1: Dermal absorption value for trisodium hydrogen EDTA (CAS 150-38-9-4) (calculated with Dermwin v 2.02, Epi Suite 4.1)


Structural formula

Flux (mg/cm2/h)

trisodium hydrogen EDTA 


3.44 E-05

If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2017). In vivo skin irritation studies with the analogue substances disodium dihydrogen- and tetrasodium EDTA (CAS 139-33-3 and CAS 64-02-8) revealed no skin corrosive or irritation properties, thus no damage to the skin surface is expected to lead to an enhanced penetration.

Overall, based on the physico-chemical and the available toxicological data, dermal uptake of trisodium hydrogen EDTA is considered to be low.


In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract (ECHA, 2017). No granulometry data,of trisodium hydrogen EDTA is available as the substance is only handled in solution and identified uses do not include spray applications. The vapour pressure of trisodium hydrogen EDTA solution was estimated to be < 7 mPa at 25 °C, thus being of low volatility (ECHA, 2017).

Moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. Vapours of very hydrophilic substances may be retained within the mucus (ECHA, 2017). Thus, taking into account a log Pow of -3.8 absorption of trisodium hydrogen EDTA will be limited, if the substance is inhaled.

A 90-day inhalation study with disodium dihydrogen EDTA (CAS 139-33-3) to rats did not reveal any substance related systemic toxic effects up to and including the highest concentration tested, 15 mg/m3. Based on the results of this inhalation repeated dose toxicity studies with disodium dihydrogen EDTA, no conclusion on the absorption of the test substance via inhalation is possible.

In conclusion, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance can be considered negligible. However, if the substance is inhaled, the absorption of the substance will be low.

Distribution and Accumulation

Distribution of a compound within the body depends on the rates of the absorption and the physico-chemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores. The rate at which very hydrophilic molecules diffuse across membranes could limit their distribution (ECHA, 2017).

Trisodium hydrogen EDTA has a medium molecular weight and good water solubility. Based on the physico-chemical properties and if absorption occurs, distribution within the body can be considered as very likely. After absorption, trisodium hydrogen EDTA may enter the blood circulating system through which it will be distributed within the body.

Highly lipophilic substances in general tend to concentrate in adipose tissue, and depending on the conditions of exposure may accumulate. Although there is no direct correlation between the lipophilicity of a substance and its biological half-life, it is generally the case that substances with high log Pow values have long biological half-lives. The low log Pow of -3.8 implies that trisodium hydrogen EDTA may not have potential to accumulate in adipose tissue (ECHA, 2017). This is also supported by the fact that in rats 99% of an oral dose of 475 mg/kg bw of disodium dihydrogen EDTA are excreted within 32 h (6% via urinary excretion and cumulated to 93 % via the feces)(Yang, 1964). Based on this information the bioaccumulation potential of trisodium hydrogen EDTA is considered to be very low.


Prediction of compound metabolism based on physico-chemical data is very difficult. Structure information gives some but no certain clue on reactions occurring in vivo. The potential metabolites following enzymatic metabolism were predicted using the QSAR OECD toolbox (v4.2, OECD, 2018). This QSAR tool predicts which metabolites may result from enzymatic activity in the liver and in the skin, and by intestinal bacteria in the gastrointestinal tract. No hepatic dermal metabolites were predicted for the test substance, respectively. Up to 12 metabolites were predicted to result from all kinds of microbial metabolism for the test substance. Most of these metabolites were found to be a consequence of the degradation of the molecule by microbial metabolism.

Available genotoxicity data with trisodium hydrogen EDTA do not show any genotoxic properties of the test substance. An Ames-test, an in vitro cytogenicity/chromosome aberration test and an in vitro mouse lymphoma assay test were consistently negative with and without metabolic activation. Also an in vivo micronucleus test with the source substance disodium dihydrogen EDTA (CAS 139-33-3) was negative. Thus, there was no evidence for differences in genotoxic potencies due to metabolic changes in genotoxicity tests.


The major routes of excretion for substances from the systemic circulation are the urine and/or the feces (via bile and directly from the GI mucosa). Only limited conclusions on excretion of a compound can be drawn based on physico-chemical data. Low molecular weight (below 300 g/mol in rats), good water solubility, and ionization of the molecule at the pH of urine are characteristics favorable for urinary excretion. Based on the good water solubility and medium molecular weight, excretion of absorbed substance via urine is expected.

Short summary

There is no  experimental data available on the toxicokinetic behavior of trisodium hydrogen EDTA (CAS 150-38-9).

Based on its physico-chemical properties oral and inhalation absorption of trisodium hydrogen EDTA is considered low. Dermal absorption is assumed to be very low. If absorbed, trisodium hydrogen EDTA will presumably be distributed in the body and predominantly excreted via urine. Its bioaccumulation potential is considered to be very low.


ECHA (2017) Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Yang, S.S. et al. (1964) Summaries of toxicological data. Fd. Cosmet. Toxicol. 2, 763-767

OECD (2018). OECD QSAR Toolbox v 4.2, 2018, Laboratory of Mathematical Chemistry Oasis. Downloaded from Prediction performed on 25 October 2018.

US EPA. 2012: Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.1.; Prediction of dermal flux rate: DERMWIN v.2.02 (September 2012); United States Environmental Protection Agency, Washington, DC, USA; Prediction performed on 25 October 2018.