potassium;2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetate;dicalcium

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

general toxicokinetic assessment

Type of information:

other: summary of available information

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Review of toxicokinetics based on available information (Reliability 2)

Justification for type of information:

All available information on the test substance was used to assess the potential toxicokinetics, based on the REACH Guidance on Toxicokinetics (Reach Guidance 7c).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

R.7.12 Guidance on Toxicokinetics

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

A toxicant can enter the body via the gastrointestinal tract, the lungs and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration.1
As the test substance KCa2DTPA is used as a fertilizer, it is expected that it will be highly water soluble, in order to have the potassium and calcium available for plant uptake; the chelate is expected to have a water solubility of > 1 g/mL. It will therefore readily dissolve into the gastrointestinal fluids and make contact with the mucosal surface. As the pKa is high, the test substance is a weak acid, and not expected to dissociate into ions in aqueous solution, and will therefore not hamper the absorption. However, the molecular weight of KCa2DTPA (>500) is less favorable for absorption. Moreover, the log Kow (-13.49) will severely limit the uptake through the lipid membranes. For risk assessment purposes the oral absorption of KCa2DTPA is set at 10%. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

The low vapour pressure (≤ 8.27E-25 mm Hg at 25°C) and the absence of a boiling point (reaction and/or decomposition of the test substance starts at 125°C) indicate that KCa2DTPA is a substances with low volatility. Therefore it is not likely that KCa2DTPA will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region via inhalation of vapour.
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. KCa2DTPA is a solid, with unknown mean particle size. It cannot be excluded that at least part of the substance will reach the nasopharyncheal region and subsequently the tracheo/bronchial/pulmonary region via inhalation. If KCa2DTPA reaches the tracheobronchial region, it is likely to diffuse/dissolve into the mucus lining of the respiratory tract due to its water solubility. However, further uptake through the lipid membranes will be hampered due to the low log Kow (≤ -13.49). For risk assessment purposes the inhalation absorption of KCa2DTPA is set at 10%. The inhalation toxicity data do not provide reason to deviate from the proposed oral absorption factor.

KCa2DTPA is a powder, however, the substance is used/marketed as a liquid. Due to the high water solubility, it will dissolve easily into the surface moisture of the skin to allow uptake. However, the molecular weight of KCa2DTPA (>500) is less favorable for absorption. Moreover, the log Kow (-13.49) will severely limit penetrance of the first skin layer, the stratum corneum (non-viable layer of corneocytes forming a complex lipid membrane).
According to the criteria given in the REACH Guidance2, a default value of 100% dermal absorption should be used unless MW >500 and log Kow <-1 or >4, in which case a value of 10% skin absorption should be chosen. For KCa2DTPA the criteria for 10% absorption are met.
Based on these considerations, for risk assessment purposes the dermal absorption of KCa2DTPA is set at 10%.


Once absorbed, distribution of the test substance throughout the body is expected based on its water solubility. One calcium is less strongly bonded, but no further metabolism is expected. The absorbed KCa2DTPA is expected to be excreted mainly via urine. Based on its low partition coefficient, water solubility and moderate to high molecular size, KCa2DTPA is not expected to accumulate significantly in adipose tissue.

Applicant's summary and conclusion

Conclusions:

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of KCa2DTPA, absorption factors for this substance are derived to be 10% (oral), 10% (inhalation) and 10% (dermal) for risk assessment purposes. No significant bioaccumulation potential is expected.