15 48 15 8 25 15 1321 15 8 25 0825002 15 8 25 6 8 15 2 18 15 6 27 2 15 3 13 28 35 (1) 51 198 7 (2) 3 6 1 100g (1) 1 (1) 1 2 1
astaxanthin;3,3 -dihydroxy-, -carotene-4,4 -dione (2) 1 2 C40H52O4 596.86 97.0 102.0 (3) 1 1933 R.Kuhn Astacus gammarus 1935 P.Karrer 1938 R.Kuhn Leftwick Weedon 1967 1982 A U 1990 2 Council Directive 70/524/EEC Annex 100ppm 80ppm (4) 22 233 8 4 16 120 (1) 10 0 125 250 500 1000 2000mg/kg Füllinsdorf 10 1 1 10 LD50 2000mg/kg 4 13 Füllinsdorf 16 0 310 620 1240mg/kg / 13 2
5 25 3 3 0 40 80 160mg/kg / 3 6 (2) Füllinsdorf 40 0 250 500 1000mg/kg / 7 16 7 20 0 100 200 400mg/kg / 7 19 8 Wilson 9 (3) 0.05mg S.typhimurium TA1535 TA1537 TA1538 TA98 TA100 5 5 S9-Mix 10 3
500 1000 2000mg/kg 2 30 6 Füllinsdorf 11 (4) 40 400 mg/kg 91 12 20 mg/kg 400 mg/kg 8 1 (5) 4 3 16 4 A 201 (6) - - 14 17 4
1) 2) 3) (ADI) 1 2 3 H. Hencken,,p.79 p.99, 16,(1991). 4 10 5 13 6 13 7 8 9 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 12 13 14 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), 215-223(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) 3383-3392 (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
15 48 15 8 25 15 1321 15 8 25 0825002 15 8 25 6 8 15 2 18 15 6 27 2 15 3 13 28 35 (1) 51 198 7 (2) 14 4 1 80g (1) 1 (1) 1 2 canthaxanthin, -carotene-4,4 -dione 1
(2) 2 C40H52O2 564.86 CAS 514-78-3 96.0 102.0 209 (3) 1 1950 Cantharellus cinnabarinus O.Isler 1956 A 1963 1966 EU Council Directive 70/524/EEC Annex 25mg/kg 8mg/kg FAO/WHO JECFA 1995 (ADI) 0-0.03mg/kg / (4) (1) 14C 14C- 2 ml 1 1 1 46-89 7 98 PGV/LacIbm 2
100 mg/kg 5 10 1 2 1 6 1 14C- 0.2 0.6 mg/kg 1 14C- 84 89 1.6% 3.6 1.6% 4.6 3% 7 14C- 14C- 0.2 0.6 mg/kg 1 2 14C- 96 1 7.4 100 1 (2) 1) 1 10 ICR-SLC 1,250 2,500mg/kg 500 1,000mg/kg 14 1 LD50 2,500mg/kg 1,000mg/kg 4 1 10 SD-SLC 2,500 5,000mg/kg 500 1,000mg/kg 14 1 LD50 5,000mg/kg 1,000mg/kg 4 2) 6 1 1 0 1 4g 3
15 4g/ / 5 3) Wistar 0 0.5 2.0 5.0% 998 25 25 25 15 0 0.5 2.0 6 5 CD Sprague-Dawley 50 0 0 5 25 75 250mg/kg / 104 10 52 10 78 30 104 26 51 78 104 10 51 104 25mg/kg / 25mg/kg / 17 51 104 250mg/kg / 104 75 250mg/kg / 25mg/kg / 78 5mg/kg / 75 250 mg/kg / 25 mg/kg 52 75 250 mg/kg / (52 104 ) 75 250mg/kg / 78 78 75 250 mg/kg / 4
104 75 250 mg/kg / 52 25mg/kg / 78 104 5 25mg/kg / 250mg/kg / 52 25 75 250mg/kg / 78 5 mg/kg / 6 7 ( 50 49 1 3 4 11 / ) 0 0 0.2 0.6 1.8 5.4 16 49 mg/kg / 3 2 4 / / 0 200 500 1000mg/kg / 3 0.2 49mg/kg / 3 1 2 200 1000mg/kg / 3 3 slit-lamp biomicroscopy 200mg/kg / 18 8 1000mg/kg / 49mg/kg / 2 1 1 2 3 1.8 5.4mg/kg / 16 49mg/kg / 0.6mg/kg / 2.5 3 49mg/kg / 0 0.2mg/kg / 5
1 49mg/kg / 16 mg/kg / 0.2mg/kg / 8 4) 20 Wistar 0 1,000mg/kg 16 F1 15 F1 39 43 F 1 F F1 F 2 1 1 3 F0 F1 5 5) H17 rec M45 rec WP2B/ hcr hcr W3110 thy pol P3478 thy pol 2,000 g/disc 2 10 9 TA98 TA100 4 40 400 4,000 g/plate 2 S-9Mix preincubation 9 6) In vitro 6
1.2mg/L 14.2g/kg 12 28g/kg / 1 4 0.2 0.5 1.8 20 50mg /kg 42 8 mg/kg 0.5mg/kg / 20 50mg/kg 0.2 0.5 1.3mg/kg 18 50mg/kg / 1 5 12 12 4 11mg/kg / 40 34.5 3 16 20-30 g/g 7
49 g/kg / 36 83 54 / 7 154ng/g 100 7) 32 25 7 411 95 (21 ) 15 240mg/ 58.1 mg/ 45mg/ 1 14 3.1 2 0.6 201g 30.3g 13.9g p 0.0001 30mg 3,000mg 10 b 27 5 15mg/ 5 60mg/ 90 120mg 10 ( 170g) 5 15mg/ b 5 60mg/ b 5 90mg/ b b b b b b 15mg/ 0.25mg/kg / 11 12 19 11 8 6/9 2 3 8
1 12 178g 14 5 70% 1 12 150g 10 61 11 8) 10 1 (LDL) LDL (3) 9
JECFA ADI 0-0.03mg/kg / ADI ADI 0.025mg/kg / ADI 5 0.25mg/kg / 10 10
1 2 3 JECFA Monograph 839.Canthaxanthin(WHO Food Additives Series 35) 4 5 6 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) : 89-104(1995). 11 Arden GB, B. F., Canthaxanthin and the eye : A critical ocular toxicological assessment., J. Toxicol.-Cut & Ocular Toxicol, 10 : 115-155(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 : 439-450(1989). 13 Leyon, H., Ros, A.M., Nyberg, S., and Algvere, P., Reversibility of Canthaxanthin deposits within the retina., Acta Ophthalmologica, 68:607-611(1990). 11