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Key value for chemical safety assessment

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An ADME study is not available. In acute dermal and oral studies no abnormalities were found at macroscopic post mortem examination of the animals. No mortalities occurred and the LD50s were >2000 mg/kg bw. The results from a repeated dose toxicity study (extended OECD 422, 90 -day) also revealed a low toxicity, the NOAEL is 500 mg/kg bw/day based on effects in the large intestine.

Therefore, an extensive toxicokinetic assessment is considered of limited value. Below an assessment of the anticipated toxicokinetic behaviour is given.

The water solubility of is high (the complexation product will always be placed on the market as an 65% or 90-92% aqueous solution) and therefore in principle not considered a rate limiting factor for the absorption of the compound from the gastro-intestinal tract.

Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily, and the log Pow was calculated/measured to be <0, it is expected that the complexation products will be hardly absorbed through the skin.

Because of the high water solubility, the compound or its metabolites will be readily excreted via the kidneys. At relatively high doses of 500 -2000 mg/kg bw kidney toxicity was seen.

Based on the information on the constituents of the complexation products it is expected the substance will be readily excreted. In one study the half-life of L(+) tartrate was 4.6 and 4.8 hours from the urine of male and female rats, respectively. In another study half-lives from bone and blood were 9 and 5.9 days for L(+) tartrate and 2.5 or 6.5 days for DL(-) tartrate, respectively (WHO food additives series 12, Tartaric acid and monosodium tartrate). Iron plays an important role in physiology and has limited bioavailability and homeostasis is tightly controlled (Papanikolaou and Pantopoulos, 2005). Sodium chloride plays an important role in physiology and is readily absorbed and excreted via the kidneys without undergoing any chemical change (www. saltinstitute. org).

Therefore, accumulation in the body during prolonged exposure is not anticipated for the complexation products.

For further details see attached document.