Ethylenediaminetetraacetonitrile

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: Based on the expected kinetic behaviour in the body EDTN accumulation in the body during prolonged exposure is not anticipated.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The acute oral and dermal toxicity of EDTN is low, with the LD50 being higher than 2000 mg/kg bw (dermal) and 5000 mg/kg bw (oral). The OECD 421 (6 -wk study) also revealed that EDTN has a low toxicity. Therefore, an extensive toxicokinetic assessment is considered of limited value. Below, an assessment of the anticipated toxicokinetic behaviour of EDTN is given. The water solubility of EDTN is moderate (0.3 g/L), and therefore not considered a rate-limiting factor for the absorption of the compound from the gastro-intestinal tract. Generally, the bioavailability of PDTN from the gastrointestinal tract is anticipated to be high (1). However, bioavailability (systemic exposure) may be decreased because of extensive first-pass metabolism. After absorption of EDTN, dealkylation of the tertiary nitrogens is anticipated. This metabolic route is mediated by the P450 enzyme system (2). Conjugation of the dealkylated nitrogen with glucuronide is an expected next step in the metabolism of EDTN. Another possibility for the metabolism of EDTN is that one or more of the cyano groups are displaced by glutathione (3). Extensive metabolism of the compound might lead to enzyme induction, which might cause the observed systemic effects increase in alanine aminotransferase activity and the increased Iiver to body weight ratio as well as the centrilobular hepatocyte hypertrophy after treatment with 1000 mg/kg bw as seen in the 28 -day toxicity study with the structurally related substance PDTN (see also section 13). Generally, this phenomenon is more considered an adaptation mechanism rather than a toxic effect. Glutathion conjugates formed in the liver can be excreted intact in bile, or they can be converted to mercapturic acids in the kidney and excreted in urine. EDTN will probably show a small volume of distribution because of its low partition coefficient. Accumulation in fatty tissues is not anticipated. Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily (4), it is to be expected that EDTN will not penetrate the skin to a large extent. Based on the expected kinetic behaviour in the body, as described above, EDTN accumulation in the body during prolonged exposure is not anticipated.

1. L.S. Schanker et al. Absorption of drugs from the rat small intestine (1958) J. Pharmacol. Exp. Ther. 123, 81 -88

2. A. Parkinson (1996). In: Casarett and Doull's Toxicology, The basic science of poisons, fifth edition. Eds. C.O. Klaassen, M.O. Amdur and J. Doull. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, p 144

3. A. Parkinson (1996). In: Casarett and Doull's Toxicology, The basic science of poisons, fifth edition. Eds. C.D. Klaassen, M.O. Amdur and J. Doull. Chapter 6: Biotransformation of xenobiotics. McGraw-Hill, New York, p 178

4. T.G. Vermeire et al. (1993), Estimation of consumer exposure to chemicals: application of simple models. The Science of the Total Environment 136, 155 -176