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Description of key information

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Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

The acute oral, dermal and inhalation toxicity of the read across substance GLDA-Na4 is low with the LD50 values being higher than 2000 mg/kg bw and the 4 -h LC50 value being higher than 4.2 mg/L (technically highest attainable concentration). The repeated dose toxicity studies (90 -day, developmental and 2 -generation study) also revealed that GLDA-Na4 has a low toxicity. Therefore, an extensive toxicokinetic assessment is considered of limited value. Below an assessment of the anticipated toxicokinetic behaviour of GLDA-Na4/GLDA-H4 is given.

The water solubility of GLDA is very high (>60% wt) and therefore in principle not considered a rate limiting factor for the absorption of the compound from the gastro-intestinal tract. However, the size of the molecules is quite large. Urine samples collected in rats at the end of a 90 -day oral gavage study, showed levels of 2 and 1.3% of the nominal intake in males and females, respectively. An absorption study (single gavage dose of 1000 mg/kg bw) in rats revealed an absorption up to 5%.

Therefore, also based on data on other chelates like EDTA-H4 and EDTA-Na4, for organic, soluble GLDA-Na4 the intestinal absorption was estimated to be 5%. Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily, and the log Pow of GLDA-Na4 was measured to be <0 and calculated to be -11.95, it is expected that GLDA-Na4 will be hardly absorbed through the skin. Comparing again to EDTA-H4 and EDTA-Na4, skin absorption was estimated to be 0.001%. Based on the particle size distribution of GLDA-Na4, it is expected that at least 90% of the inhaled substance will be deposited in the upper respiratory tract, which will finally be taken up orally. Of this, only 5% will be absorbed in the gastrointestinal tract and become available systematically, i.e. 0.9 x 0.05 = 0.045 (4.5%). The other maximally 10% may reach the alveoli and it is assumed that this will be absorbed completely (worst case). Therefore, the total inhalation absorption factor will be 0.045 + 0.10 = 0.145 (14.5%). It is not expected that the GLDA moiety undergoes biotransformation. Evidence for this conclusion comes from the oral absorption study in rats that showed almost 100% recovery in urine and feces and from studies with EDTA-FeNa which indicated that both EDTA and iron are excreted unchanged following ingestion of NaFeEDTA. Because of the high water solubility, the fraction of unchanged compound that would be absorbed will be readily excreted via the kidneys (i.e. at relatively high doses of 300 -1000 mg/kg bw slight kidney toxicity was seen).

Based on the rat absorption study, it was indeed found that when a limited amount of GLDA-Na4 is being absorbed, on average >85% is rapidly (first 24 hours) excreted via urine/faeces by the animal. Based on the expected kinetic behaviour in the body as described above, it is expected that GLDA-Na4 will not extensively be absorbed from the gastro-intestinal tract but when absorbed it will be readily excreted. Therefore, accumulation in the body during prolonged exposure is not anticipated.