PDF《FOREWORD》

72 weeks via feed, with a post-observation period of

30 weeks. No significant effects were observed relative to controls with respect to survival rates, body weights and relative liver weights. Only limited pathological investigations were carried out at autopsy (gross examination with histological investigation of only the liver and any tissues showing gross abnormalities). No adverse effects were observed. Therefore the NOAEL for this study was ?500mg/kg bw/day. The tolerable upper intake level for human adults was set at 3.5 g/day corresponding to approx.

58 mg/kg bw/day (USA'

s Standing Committee on the Scientific Evaluation of Dietary Reference Intakes). Choline chloride does not show a mutagenic, clastogenic or DNA damaging potential when tested in vitro;

furthermore it has no structural alerts. There is therefore no indication of a genotoxic potential in vivo. O H N + Cl OECD SIDS CHOLINE CHLORIDE UNEP PUBLICATIONS

4 No developmental toxic effects were observed in mice after oral doses of

1250 mg/kg bw/day on gestation days

1 to 18. Doses above the levels recommended currently (4160 mg/kg bw/day and higher) and associated with maternal toxicity, did produce developmental toxic effects, but these were secondary to the maternal toxicity at the excessive doses used. The compound does not produce any significant developmental toxicity in the mouse. Thus evidence from animal studies and from human exposure indicates that choline chloride has low toxicity, is not mutagenic and has no developmental toxicity. This is not unexpected in view of its presence in the diet and its production in metabolic processes in the body;

it fulfils key roles in nerve transmission, cell membrane integrity, and lipid metabolism. Only limited animal data are available on effects on fertility, but the normal exposure of humans to appreciable amounts of choline chloride both from the diet and formed from normal metabolic processes, would argue against it having any significant adverse effects on fertility. This is supported by the fact that it has been widely used as an animal feed additive for decades with no apparent adverse effects being noted on fertility. Environment Choline chloride is a white crystalline solid but is marketed as an aqueous solution (70 C

75 % w/w in water) which is a colorless liquid with an amine-like odor. It has a measured water solubility of ca.

650 g/L (calculated water solubility: 1,000,000 mg/L) and a calculated vapor pressure of 6.57*10-10 hPa at 25°C. A Henry'

s Law Constant of 2.06*10-

11 Pa*m?/mole at

25 °C could be calculated. Distribution modeling using Mackay Level I indicates water (100 %) to be the main target compartment. The amount in the other compartments is with <

0.0001 % negligible. Choline chloride is readily biodegradable according to OECD-criteria (MITI-I Test;

BOD measurements) reaching

93 % degradation within

14 days. Due to the chemical structure hydrolysis can be excluded. In the atmosphere choline chloride will be rapidly degraded according to a half life time (t?) of about 6.9 hours for hydroxyl-radicals based on a

12 hours day. Due to the measured and calculated logKow of C3.77 and C5.16 both at 25°C, respectively, and a calculated logKoc of 0.37 a bio- or geoaccumulation is not to be expected. The aquatic toxicity has been determined for freshwater and saltwater species according to several GLP and non- GLP test guidelines. For the freshwater fish species O. latipes a LC50 (96h) of >

100 mg/L and for the saltwater fish species L. limanda a LC50(96h) of >