PDF《FOREWORD》

OECD SIDS CHOLINE CHLORIDE UNEP PUBLICATIONS

1 FOREWORD INTRODUCTION CHOLINE CHLORIDE CAS N°: 67-48-1 OECD SIDS CHOLINE CHLORIDE UNEP PUBLICATIONS

2 SIDS Initial Assessment Report For SIAM

19 Berlin, Germany, 19-22 October

2004 1.

Chemical Name: Choline chloride 2. CAS Number: 67-48-1 3. Sponsor Country: United Kingdom Dr Steve Robertson Environment Agency National Centre for Ecotoxicology &

Hazardous Substances Isis House, Howbery Park, Wallingford OX10 8BD, UK Fax: +44

1491 828

556 e-mail: [email protected] 4. Shared Partnership with: BASF AG, Germany;

Air Products Chemicals, The Netherlands;

Taminco NV, Belgium 5. Roles/Responsibilities of the Partners: x Name of industry sponsor /consortium Akzo Nobel Chemicals NV Chris Braun Stationsplein

4 3800 AE Amersfoort The Netherlands x Process used 6. Sponsorship History x How was the chemical or category brought into the OECD HPV Chemicals Programme ? This substance is sponsored by the UK under the ICCA Initiative and is submitted for first discussion at SIAM

19 7. Review Process Prior to the SIAM: The industry consortium collected new data and prepared the updated IUCLID, and draft versions of the SIAR and SIAP. UK government peer-reviewed the documents and audited selected studies. 8. Quality check process: 9. Date of Submission:

23 July

3004 10. Date of last Update: 11. Comments: OECD SIDS CHOLINE CHLORIDE UNEP PUBLICATIONS

3 SIDS INITIAL ASSESSMENT PROFILE CAS No. 67-48-1 Chemical Name Choline chloride Structural Formula SUMMARY CONCLUSIONS OF THE SIAR Category/Analogue Rationale In some circumstances, available data for other choline salts (e.g. choline magnesium salicylate) have been evaluated in Human Health to assist the weight of evidence approach for choline chloride. Due consideration was given to potential toxicity exerted by byproducts e.g. in parenteral exposure. Human Health Choline is a dietary component and found in foods as free choline and as esterified forms such as phosphocholine, glycerophosphocholine, sphingomyeline, and phosphatidylcholine. It functions as a precursor for acetylcholine, phospholipids, and the methyl donor betaine and is important for the structural integrity of cell membranes, methyl metabolism, cholinergic neurotransmission, transmembrane signaling, and lipid and cholesterol transport and metabolism. Dietary choline is absorbed from the lumen of the small intestine. Additionally to dietary supply choline can be made available by enzymatic cleavage in the pancreas from other nutritional sources (e.g. phosphatidylcholine). Before choline can be absorbed from the gut, some is metabolised by bacteria to form betaine and methylamines. Fasting plasma choline concentrations vary from

9 to

20 ?mol/L. The critical adverse effect from high intake of choline is hypotension, with corroborative evidence on cholinergic side effects (e.g., sweating and diarrhoea) and fishy body odour. After inadequate dietary intake decreased choline stores and liver damage (as assessed by elevated alanine aminotransferase) may develop. Animal studies with choline chloride show a low acute toxicity after oral uptake (with a range of LD50s of

3150 C ?5000 mg/kg bw determined in different studies). . No acute toxicity attributable to choline was observed in humans following oral doses of ?3000 mg choline magnesium trisalicylate/day. In rabbits, choline chloride may lead to a slight irritation of the skin and eye. No data on sensitization in animals are available. The skin sensitisation potential of choline chloride is regarded as negligible in humans. In a limited, specialised, repeated dose study designed to investigate the impact of choline on the liver tumour promoting activity of phenobarbital and DDT in DEN-initiated animals, rats were dosed with approximately 500mg/kg bw/day over