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1 (1) (2) g (1) 1 (1) 1 2 1

2 astaxanthin;3,3 -dihydroxy-, -carotene-4,4 -dione (2) 1 2 C40H52O (3) R.Kuhn Astacus gammarus 1935 P.Karrer 1938 R.Kuhn Leftwick Weedon A U Council Directive 70/524/EEC Annex 100ppm 80ppm (4) (1) mg/kg Füllinsdorf LD mg/kg 4 13 Füllinsdorf mg/kg / 13 2

3 mg/kg / 3 6 (2) Füllinsdorf mg/kg / mg/kg / Wilson 9 (3) 0.05mg S.typhimurium TA1535 TA1537 TA1538 TA98 TA S9-Mix 10 3

4 mg/kg Füllinsdorf 11 (4) mg/kg mg/kg 400 mg/kg 8 1 (5) A 201 (6)

5 1) 2) 3) (ADI) H. Hencken,,p.79 p.99, 16,(1991) Joosten, H.F.P., Hoekstra, A., Geelen,J.A.G., and Yih, T. D., Cysts in Rabbit Foetal Brains / Malformation or Artefacts?, Toxicology 47, 25-37(1981). 10 Ames 11 in vivo Bernstein, P.S. et al, Identificaion and Quantitation of Carotenoids and their Metabolites in the Tissues of the Human Eye, Exp. Eye Res.72(3), (2001). 15 Khachik, F. et al, Transformation of Selected Carotenoids in Plasma, Liver, and Ocular Tissues of Humam and in Nonprimate Animal Models, IOVS. 43 (11) (2002). 16 Glatzle, D. and Bausch, J., Comparison of Astaxanthin and Canthaxanthin balance studies (1988) 17 Bausch, J., Plasmakinetics of Astaxanthin and Canthaxanthin in Humans(1987) 5

6 (1) (2) g (1) 1 (1) 1 2 canthaxanthin, -carotene-4,4 -dione 1

7 (2) 2 C40H52O CAS (3) Cantharellus cinnabarinus O.Isler 1956 A EU Council Directive 70/524/EEC Annex 25mg/kg 8mg/kg FAO/WHO JECFA 1995 (ADI) mg/kg / (4) (1) 14C 14C- 2 ml PGV/LacIbm 2

8 100 mg/kg C mg/kg 1 14C % % 4.6 3% 7 14C- 14C mg/kg C (2) 1) 1 10 ICR-SLC 1,250 2,500mg/kg 500 1,000mg/kg 14 1 LD50 2,500mg/kg 1,000mg/kg SD-SLC 2,500 5,000mg/kg 500 1,000mg/kg 14 1 LD50 5,000mg/kg 1,000mg/kg 4 2) g 3

9 15 4g/ / 5 3) Wistar % CD Sprague-Dawley mg/kg / mg/kg / 25mg/kg / mg/kg / mg/kg / 25mg/kg / 78 5mg/kg / mg/kg / 25 mg/kg mg/kg / ( ) mg/kg / mg/kg / 4

10 mg/kg / 52 25mg/kg / mg/kg / 250mg/kg / mg/kg / 78 5 mg/kg / 6 7 ( / ) mg/kg / / / mg/kg / mg/kg / mg/kg / 3 3 slit-lamp biomicroscopy 200mg/kg / mg/kg / 49mg/kg / mg/kg / 16 49mg/kg / 0.6mg/kg / mg/kg / 0 0.2mg/kg / 5

11 1 49mg/kg / 16 mg/kg / 0.2mg/kg / 8 4) 20 Wistar 0 1,000mg/kg 16 F1 15 F F 1 F F1 F F0 F1 5 5) H17 rec M45 rec WP2B/ hcr hcr W3110 thy pol P3478 thy pol 2,000 g/disc TA98 TA ,000 g/plate 2 S-9Mix preincubation 9 6) In vitro 6

12 1.2mg/L 14.2g/kg 12 28g/kg / mg /kg 42 8 mg/kg 0.5mg/kg / 20 50mg/kg mg/kg 18 50mg/kg / mg/kg / g/g 7

13 49 g/kg / / 7 154ng/g 100 7) (21 ) mg/ 58.1 mg/ 45mg/ g 30.3g 13.9g p mg 3,000mg 10 b mg/ 5 60mg/ mg 10 ( 170g) 5 15mg/ b 5 60mg/ b 5 90mg/ b b b b b b 15mg/ 0.25mg/kg / /

14 g % g ) 10 1 (LDL) LDL (3) 9

15 JECFA ADI mg/kg / ADI ADI 0.025mg/kg / ADI mg/kg / 10 10

16 1 2 3 JECFA Monograph 839.Canthaxanthin(WHO Food Additives Series 35) Buser, S., Canthaxanthin in a long-term study with male rats (feed mixture), (1992). 7 Buser, S., Canthaxanthin in a long-term study with female rats (feed mixture), (1992). 8 Buser, S.,Bausch, J., Goralczyk,R., Lenzs,B., Schuep,W., Bee, W., and Zuhlke,U., Canthaxanthin in a long-term study with Cynomolgus Monkeys, (1994). 9 ß 8 10 Kopcke, W, B. F., Schalch W, Canthaxanthin deposition in the retina : a biostatisitical evaluation of 411 patients, J. Toxicol.-Cut & Ocular Toxicol, 14(2) : (1995). 11 Arden GB, B. F., Canthaxanthin and the eye : A critical ocular toxicological assessment., J. Toxicol.-Cut & Ocular Toxicol, 10 : (1991). 12 Arden GB, Oluwole JOA, Polkinghorne P. et al Monitoring of Patients taking Canthaxanthin and Carotene : An Electroretinographic and Ophthalmological Survey., Human Toxicol. 8 : (1989). 13 Leyon, H., Ros, A.M., Nyberg, S., and Algvere, P., Reversibility of Canthaxanthin deposits within the retina., Acta Ophthalmologica, 68: (1990). 11

CAS NC(CH 2 ) 4 CN 1,4- C 6 H 8 N c.c d = Pa

CAS NC(CH 2 ) 4 CN 1,4- C 6 H 8 N c.c d = Pa 1 200117 21512 CAS 111693 110 NC(CH 2 ) 4 CN 1,4- C 6 H 8 N 2 108.14 1 99 2-1. 2 1 295 159 c.c. 550 3 1.7-4.9 20 d 0.965 4 3.73 = 1 0.3 Pa 0.002 mmhg20 2 log Pow-0.32 m/z 41, 1.0 68 0.54 54 0.43 4 Koc9-16