Sodium [N-[2-[bis(carboxylatomethyl)amino]ethyl]-N-(2-hydroxyethyl)glycinato(3-)]zincate(1-)

Endpoint summary

Link to relevant study record(s)

Reference

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).

Objective of study:

toxicokinetics

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

R.7.12 Guidance on Toxicokinetics

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
The substance is a reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA. As the test substance is used as a fertilizer, it is expected that it will be highly water soluble, in order to have the zinc available for plant uptake; each 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. The molecular weight of each chelate in the reaction mixture (<500) is favorable for absorption. 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 log Kow (≤ -10.32) will severely limit the uptake through the lipid membranes. For risk assessment purposes the oral absorption of the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is set at 10%.2 The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

The low vapour pressure (≤ 9.9E-20 mm Hg at 25°C) and the absence of a boiling point (reaction and/or decomposition of the test substance starts at 150°C) indicate that the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is a substances with low volatility. Therefore it is not likely that the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA 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. The reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA 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 the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA 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 of the components (≤ -10.32). For risk assessment purposes the inhalation absorption of the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is set at 10%.2 The inhalation toxicity data do not provide reason to deviate from the proposed oral absorption factor.

The reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA 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. The moderate size of each components (approximately 350-450 Da) is not expected to hamper uptake, however the low log Kow of the components (≤ -10.32) 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. Although the MW (350-450) of the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA indicate that the criteria for 10% absorption are not met, the extremely low log Kow will severely limit absorption.
Taken together, based on molecular weight, some dermal absorption might be expected, but the extremely low log Kow will severely limit absorption. The oral absorption of the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is set at 10%. Based on these considerations, for risk assessment purposes the dermal absorption of the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is set at 10%.2

Once absorbed, distribution of the test substance throughout the body is expected based on its water solubility and moderate molecular weight. No metabolism is expected and the absorbed reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is expected to be excreted mainly via urine3. Based on its low partition coefficient, water solubility and moderate molecular size the reaction mixture of ZnEDTA, ZnDTPA and ZnHEEDTA is not expected to accumulate significantly in adipose tissue.
 

Conclusions:

A toxicokinetic assessment was performed based on the available data of the substance. Based on the physical/chemical properties of the reaction mass of ZnEDTA, ZnDTPA and ZnHEDTA, 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.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10