1 1 1 2 2 2 2 2 3 3 (1) 4 (2) 5 5 6 8 9 10 11 12 12 14 (1) JECFA 14 (2) FDA 14 (3) EU 14 (4) 2005 15 15 15 1 2005 16 2 2005 17 17 22 23
- 1 -
Newberyite 50), 51), 52) Generally Recognized as SafeGRASGMP ph 7), 30) EU infant formulafollow-on formula 14 7 FAO/WHO JECFA EU 46 17 3 28 Magnesium hydrogen phosphate MgHPO 4 3H 2 O 174.33 CAS 7757-86-0JECFA - 2 -
7782-75-4FCC 27 20), 21) 43) Mg 2+ PO 3-4 - 3 -
0.25-0.65 mmol7.8-20.1 mg/g protein 85% 13 mmol/l40 mg/dl 1 mmol/l3.1 mg/dlpi 0.1% 29) MgMg Mg active transport passive diffusion Mg 130140% 180% active transport system Mg passive diffusion1030% Mg 31), 56), 57) Mg 2+ 3040% Mg 36% Mg 25% 5060% Mg 8) Mg 4 2 Mg 2128 g 1 mole 70 kg 14.3 mmol/kg 0.034% 31) Mg 5060% 1/3 Mg 15), 45) Mg 0.75-0.95 mmol/l1.8-2.3 mg/dl - 4 -
Mg 2128g 60% 20%Mg Mg 38% 12% Mg 35% 8) Mg carrier-mediated transport system Mg Mg 15), 46), 47) Mg 2+ Mg 71% 8) Mg 0.1 1.0 mm 8) Mg Mg 2+ MgX Mg Mg 160 mg/ 200 mg/400 mg/ Mg 160 mg/ 400 mg/ Mg 16) 4 344 521 mg/ 210 362 mg/ 112 124 mg/ 38.9% 30.6% 17) - 5 -
LD 50 1,3003,700 mg/kg 1,3804,100 mg/kg 10) LD 50 1,660 mg/kg / LD 50 2,500 mg/kg / 10) LD 50 1,050 2,800 mg/kg 32) SD 10 00.51.55.0%0 0.250.752.5 g/kg / 90 27 5.0% 1 1.5 5.0%5.0% 0.5% 5.0% 33), 42) 1.5% NOAEL0.25 g/kg / 20 012.55.0%0 0.51.252.5 g/kg / 5.0%2.5 g/kg / 16 5.0% 5.0% 2.5% 5.0% 2.5% 5.0% JECFA ) (kg) (g//) (g/kg /) 0.02 3 150 0.4 20 50-6 -
2.5% 10), 44) NOAEL 1%0.5 g/kg / 5.0% 2.5 g/kg / 5 0.22.010%0.1 1.05 g/kg / 0.22.010%0.11.0 5 g/kg / 1 10%5% 10% 10% 2% 2% 10%0.2% 10) 2.0% NOAEL 0.1 g/kg / 50 0.050.55.0% 0.0250.252.5 g/kg / 2 5% 0.5% 10) 5% NOAEL 0.25 g/kg / 50 0.050.55.0% 0.0250.252.5 g/kg / 2 5% 0.5% 10) 5% NOAEL 0.25 g/kg / F344 10 00.10.52.5% 0623081,600 mg/kg / 0592991,531 mg/kg / 90 2.5% - 7 -
2.5% 0.1 0.5% 2.5% 0.5 2.5% 34) 2.5%2.5% NOAEL 308 mg/kg / 299 mg/kg / B6C3F 1 10 00.30.6 1.252.55% 06101,2202,6905,41011,400 mg/kg / 0770 1,5803,2606,81013,830 mg/kg / 13 5% 2.5 5% 5% 2.5 5%2.5 5% 2.5 5% 5% 35) 2.5% NOAEL LOAEL 5,410 mg/kg / 6,810 mg/kg / B6C3F 1 50 00.52.0% 00.753.0 g/kg / 96 2% 8 36) 2% NOAEL 0.75 g/kg / B6C3F 1 50 00.52.0% - 8 -
0.753.0 g/kg / 96 8 36) Wistar 24 615 CD-1 24 616 2225 610 2022 618 10) mg/kg 370 320 465 335 130 370 238 410 282 410 169 138 240 170 166 141 128 250 0.40.75%200375 mg/kg / F 0 29 F 1 332 29 1.9% 0.8% 3) NOEL 375 mg/kg /0.75% 16 8 100 JECFA (kg) (g//) (g/kg /) 0.4 20 50-9 -
0.5%250 mg/kg / 0.05%25 mg/kg / 3), 4) NOEL 250 mg/kg /0.5% 25 mg/kg / 0.05% Wistar 22 615 0 200400 800 mg/kg / 20 14 800 mg/kg / 1 46 40) 800 mg/kg / 1,000 mg/kg / 800 mg/kg / NOEL 800 mg/kg / Salmonella typhimurium TA1535, TA1537, TA1538Saccharomyces cerevisiae D4 S9mix 10) S. typhimurium TA1530 S. cerevisiae D3 S. typhimurium TA1535, TA1536, TA1537, TA1538+/S9mix 10) S. typhimurium TA1535, TA1537, TA1538S. cerevisiae D4S9mix 10) S. typhimurium TA1530 G46 S. cerevisiae - 10 -
D3 S. typhimurium TA1535, TA1536, TA1537, TA1538+/S9mix in vivo in vitro 10) S. typhimurium TA1535, TA1536, TA1537 S9mix 10) S. typhimurium TA92, TA94, TA98, TA100, TA1535, TA1537 100 mg/ 12) S. typhimurium TA98, TA100, TA1535, TA1537, Escherichia coli WP2uvrA 5,000 µg/ 25) S9mix CHL 4.0 mg/ml 12) CHL/IU1.25 5.0 mg/mls9mix 25) S. typhimurium TA94, TA98, TA100, TA2637 100 mg/ml+/s9mix CHL 2.0 mg/ml 13) S. typhimurium TA97, TA98, TA100, TA102 10 mg/+/s9mix CHL 1.0 mg/ml 14) S. typhimurium TA1535, TA1537, TA1538, S. cerevisiae D4 TA1538 11) S. typhimurium TA1535, TA1537, TA1538, S. cerevisiae D4 11) 1 g 10) PTH - 11 -
PTH PTH 10) PTH 10) 1 kg 1.8 mg Mg 1112 Mg 1) Mg 325 1), 8) 15 2,0004,000 mg 10 2 3,900 mg 14 10) 5,0007,000 mg 1,500 mg 6,000 mg 15 10) 58) 54 3 4 10.51.02.0%P 50100200 mg/ 18-12 -
7 48 0.51.0 2.0% 30316472 144152 mg/ 0.51.0 2.0% 0.521.20 2.51 µg/ 1.042.14 5.07 µg/ 14 2.0% 14 18 0.5% 335359 mmol/kg 1.0 2.0% 360 700 mmol/kg 654 1,393 mmol/ kg 0.5 1.0 2.0%10.59.5 8.2 mg/dl 0.5% 12.813.7 mmol/kg 1.0 2.0% 60 431 mmol/kg 589 2,252 mmol/kg 18 1.0% 6 2 1 6 5 2.0% 58) SD 5 disodium ethane-1-hydroxy-1, 1-diphosphonateEHDP5 mg/kg / 10 3.0% 1 2 10 g/ 5 EHDP 1 5 EHDP 13 5 9.249.60 11.1 mg/dlehdp 7.289.04 7.72 mg/dl 5 6 2.69 gehdp 1.90 g 339 mmol/kgehdp 157 mmol/kg - 13 -
EHDP 58) JECFA JECFA 1986 29 23) Ionizable salts ADI Mg 7 ADI ADI 70 mg/kg / 1982 26 10) 26 6,600 mg ADI070 mg/kg / MTDI70 mg/kg /Mg FDA GRAS Mg Mg Mg 300 mg/ Mg 11) EU EU SCF1990 MgCa ADI not specified Mg JECFA MTDI 70 mg/kg / 61), 1) SCF 2001 UL Mg UL Mg 12 250 mg// NOAEL - 14 -
250 mg//uf 1 NOAEL UL 250 mg// Mg UL 4 13 13 UL 31) 2005 16 11 2005 Mg Mg 350 mg//8 5 mg/kg / 62, 2) 1 3,500 mg// 62, 2) 2 1987 45.4 22) 2 4,000 0.52 mg// 60 kg 0.0086 mg/kg / 15 65) 15 255 mg 270 mg 242 mg 1,022 mg 1,100 mg 952 mg 65) 1.3% 7 mg 543 mg 3.3 mg/ - 15 -
3.3 mg 4.2 mg3.3 25.7%%20.2%% 3.3 mg 4.2 mg 16 6.47 mg 36.68 mg 66 1 9.8 mg 41 mg 3.8% 4.0% 3.7 % 4.3% 2005 62, 2 350 mg 9.8 mg 2.8% 3,500 mg 41 mg 30% 1,2 1 2005 62, 2) mg/ 05 - - 21 - - - 21-611 - - 32 - - - 32-12 60 70 - - 55 70 - - 35 85 100 - - 80 100 - - 67 115 140 - - 110 130 - - 89 140 170 - - 140 160 - - 1011 180 210 - - 180 210 - - 1214 250 300 - - 230 270 - - 1517 290 350 - - 250 300 - - 1829 290 340 - - 230 270 - - 3049 310 370 - - 240 280 - - 5069 290 350 - - 240 290 - - 70 260 310 - - 220 270 - - - 16 -
+30 +40 - - +0 +0 - - 350 mg/ 5 mg/kg / 50% 1 9798% 1 1 2 2 2005 62, 2) mg/ 05 - - 130 - - - 130-611 - - 280 - - - 280-12 - - 650 - - - 600-35 - - 800 - - - 800-67 - - 1,000 - - - 900-89 - - 1,100 - - - 1,000-1011 - - 1,150 - - - 1,050-1214 - - 1,350 - - - 1,100-1517 - - 1,250 - - - 1,000-1829 - - 1,050 3,500 - - 900 3,500 3049 - - 1,050 3,500 - - 900 3,500 5069 - - 1,050 3,500 - - 900 3,500 70 - - 1,000 3,500 - - 900 3,500 - - +0 - - - +0-1)... (1994): 313-315. - 17 -
2) FAO and IPCS. Summary of Evaluation Performed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). ILSI Press. (1996): M-3, M-17, T-12. 7) FDA 21 CFR Parts 182 and 184. GRAS Status of Magnesium Carbonate, Magnesium Chloride, Magnesium Hydroxide, Magnesium Oxide, Magnesium Phosphate, Magnesium Stearate, and Magnesium Sulfate. Federal Register. (1985) 50: 13557-13560. 8) Altura BM. Basic biochemistry and physiology of magnesium: a brief review. Magnesium and trace elements. (1991-92) 10: 167-171. 9).. The Journal of Toxicological Sciences. (1988) 23: 31-35. 10) Twenty-sixth Report of the JECFA. International Programme on Chemical Safety (IPCS) Toxicological Evaluation of Certain Food Additives. WHO Food Additives Series 17. (1982): 151-176. 11) Life Sciences Research Office FASEB. Evaluation of the Health Aspects of Magnesium Salts as Food Ingredients. Contact No. FDA 223-75-2004. (1976). 12). 3.. (1982) 5: 579-587. 13). 4.. (1983) 6: 671-678. 14). 5.. (1984) 7: 634-643. 15) Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus Magnesium, Vitamin D, and Fluoride. National Academy Press, Washington, D.C. (1997): 190-249. 16)... (1984) 3: 7-12. 17)... (1956) 9: 18-26. 20) Revised Monograph-Magnesium Phosphate, Dibasic. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. (1996) Aug.8. 21) Magnesium Hydrogen Phosphate. JECFA Compendium. 22) FDA. 1987 Poundage and Technical Effects Update of Substances Added to Food. National Research Council, Washington, DC. Prepared for: Food and Drug Administration, Washington, DC. NTIS Report No. PB91-127266. (1989). 23) Twenty-ninth Report of the JECFA. Evaluation of certain food additives and contaminants. WHO Technical Report Series 733. (1986). 24) Twenty-sixth Report of the JECFA. Evaluation of certain food additives and contaminants. WHO Technical Report Series 683. (1982). 25). - 18 -
. The Journal of Toxicological Sciences. (1998) 23: 81-90. 29) Food and Nutrition Board Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus Magnesium, Vitamin D, and Fluoride. National Academy Press, Washington, D.C. (1997): 146-189. 30) Food and Drug Administration, HHS. 21CFR 184.1434 Magnesium phosphate. 31) European Commission. Scientific Committee on Food. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Magnesium. SCF/CS/NUT /UPPLEV/54 Final. (2001). 32) Magnesium Chloride). 7.. (1999): D-208-211. 33).. 0627010 ( 15 6 27 ). 34). F344 90. Bulletin of National Institute of Health Sciences. (2000) 118 : 63-70. 35) Tanaka H, Hagiwara A, Kurata Y, Ogiso T, Futakuchi M, Ito N. Thirteen-week oral toxicity study of magnesium chloride in B6C3F 1 mice. Toxicology letters. (1994) 73: 25-32. 36) Kurata Y, Tamano S, Shibata MA, Hagiwara A, Fukushima S, Ito N. Lack of carcinogenicity of magnesium chloride in a long-term feeding study in B6C3F 1 mice. Food and chemical toxicology. (1989) 27: 559-563. 37). 24 2 2. The Journal of Toxicological Sciences. (1998) 23: 37-49. 38). 24 4. The Journal of Toxicological Sciences. (1998) 23: 51-65. 39).. The Journal of Toxicological Sciences. (1998) 23: 67-79. 40).. Bulletin of National Institute of Health Sciences. (1996) 114: 16-20. 42). 90. 11-1428 (2000 3 2 ). - 19 -
43) NF.. 16. (1998 7 10 ). 44) Datta PK, Frazer AC, Sharratt M, Sammons HG. Biological effects of food additives. II. Sodium pyrophosphate. Journal of the Science of Food and Agriculture. (1962) 13: 556-566. 45) Elin RJ. Assessment of magnesium status. Clinical chemistry. (1987) 33: 1965-1970. 47) Romani A, Marfella C, Scarpa A. Cell magnesium transport and homeostasis: Role of intracellular compartments. Mineral and electrolyte metabolism. (1993) 19: 282-289. 50). 9..pp.806, 816-817. 51) 5505. Magnesium Phosphate, Dibasic. The Merck Index, Ninth Edition. (1976): 738. 52) Newberyite. http://euromin.w3sites.net/mineraux/newberyite.html 56) Worwag M, Classen HG., Schumacher E. Prevalence of magnesium and zinc deficiencies in nursing home residents in Germany. Magnesium research. (1999) 12: 181-189. 57) Durlach J. Magnesium in clinical practice. John Libbey Eurotext. (1988) : 1-15. 58) Haut LL, Alfrey AC, Guggenheim S, Buddington B, Schrier N. Renal toxicity of phosphate in rats. Kidney international. (1980) 17: 722-731. 59) ( 34 370 ).. 16 1 20 11. 60) Office for Official Publications of the European Communities. European Parliament and Council Directive No 95/2/EC of 20 February 1995 on Food Additives other than Colours and Sweeteners. CONSLEG: 1995L0002-29/01/2004. 61) EU Commission. Report from the Commission on Dietary Food Additive Intake in the European Union. http://europa.eu.int/comm/food/food/chemicalsafety/additives/flav15_en.pdf 62). ( 16 11 22 ) 63).. (1995) 10: 19-25. 64) Twenty-third Report of the JECFA. Evaluation of certain food additives. WHO Technical Report Series 648. (1980). 65) 15.. ( 17 4 21 ) 66). 1.( 7 ). 16. ( - 20 -
17 3 31 ) a) Principles for the safety assessment of food additives and contaminants in food. World Health Organization, International Program on Chemical Safety in Cooperation with the Joint FAO/WHO Expert Committee on Food Additives, Geneva, Environmental Health Criteria 70 (1987). 1) Commission of the European Communities. Reports of the Scientific Committee for Food (Twenty-fifth series). First Series of Food Additives of Various Technological Functions. (1990) 2). 2005 3) Weiner ML, Salminen WF, Larson PR, Barter RA, Kranetz JL, Simon GS. Toxicological review of inorganic phosphates. Food and Chemical Toxicology. (2001) 39: 759-786. 4) Summaries of toxicological data; Toxicity studies on phosphate. Food and Cosmetics Toxicology. (1964) 2: 147-154. - 21 -
Trimagnesium phosphate 33), 42) Mg 3 (PO 4 ) 2 Phosphoric acid 10) H 3 PO 4 Orthophosphoric acid 3) Disodium phosphate 10) Na 2 HPO 4 Diabasic sodium phosphate 58) NaH 2 PO 10) 4 NaH 2 PO 4 2H 2 O 10) 10), 44) Sodium orthophosphate NaH 2 PO 4 Monosodium phosphate 10) Monobasic sodium phosphate 58) Sodium triphosphate 10) 10), 4) Sodium tripolyphosphate Na 5 P 3 O 10 Sodium tripolyphosphates 10) Na 4 P 2 O 7 10) Sodium pyrophosphate 10)44) Tetrasodium diphosphate 10) Na 4 P 2 O 7 Tetrasodium pyrophosphate 10) Monopotassium phosphate 10) KH 2 PO 4 Monocalcium phosphate 10) Ca(H 2 PO 4 ) 2 Sodium acid pyrophosphate 10) Na 2 H 2 P 2 O 7 Sodium hexametaphosphate 10), 4) NaO 3 P 6 13), 32), 34), 36) Magnesium Chloride MgCl 2 Magnesium chloride hexahydrate 35), 40) Magnesium oxide 11) MgO MgCO 3 Magnesium sulfate 12), 25) MgSO 4 Magnesium stearate 11) Mg(C 18 H 35 O 2 ) 2-22 -
/ No LD 50 =1,3003,700 mg/kg 10 7 LD 50 =1,660 mg/kg 10 NaH 2 PO 4 KH 2 PO 4 Na 2 H 2 P 2 O Na 2 H 2 P 2 O 7 Na 4 P 2 O 7 Na 5 P 3 O 10 (NaPO 3 ) 6 LD 50 =1,3804,100 mg/kg 10 Na 5 P 3 O 10 LD 50 =2,500 mg/kg 10 90 10 16 20 1 5 Mg 3 (PO 4 ) 2 Na 4 P 2 O 7 00.51.55.0% 0.5% (00.250.752.50 1.55.0 2040 g/kg / ) 5.0% 27 1 5.0% NOAEL 0.25 g/kg / 012.55.0% (00.51.252.5 g/kg / ) 5.0% 5.0% 2.5% 2.5% NOAEL 0.5 g/kg / NOAEL 2.5 g/kg / 10 NaH 2 PO 4 5.0% (2.5 g/kg / ) (NaPO 3 ) 6 0.22.010% 2% (0.11.05 g/kg / 10% ) Na 5 P 3 O 10 0.22.010% (0.11.05 g/kg / 10% ) 10% NaCl (10%) Na 2 HPO 4 (5%) NOAEL 0.1 g/kg / 33 42 10 44 2 50 Na 5 P 3 O 10 0.050.55.0% 5% (0.0250.252.5 g/kg / ) NOAEL 0.25 g/kg / 10-23 -
3 / 2 50 6 15 6 16 6 10 6 18 24 24 2225 2022 (NaPO 3 ) 6 NaH 2 PO 4 KH 2 PO 4 Ca(H 2 PO 4 ) 2 Na 2 H 2 P 2 O 7 Na 4 P 2 O 7 (NaPO 3 ) 6 Na 5 P 3 O 10 0.050.55.0% (0.0250.252.5 g/kg / ) NaH 2 PO 4 KH 2 PO 4 Ca(H 2 PO 4 ) 2 Na 2 H 2 P 2 O 7 Na 4 P 2 O 7 (NaPO 3 ) 6 Na 5 P 3 O 10 5% NOAEL 0.25 g/kg / = mg/kg 370 410 - - 320 282 - - 465 410 - - 335 169 166 128 130 138 - - 370 240 - - 238 170 141 250 F 0 0.40.75% 29 (200375 mg/kg / F 1 3 32 29 ) NOAEL 375 mg/kg /0.75% 16 8 0.5% 100 (250 mg/kg / ) in vitro (+/ - S9mix) TA1535 TA1537 TA1538 D4 Ca(H 2 PO 4 ) 2 KH 2 PO 4 NaH 2 PO 4 0.05% (25 mg/kg / ) NOAEL 250 mg/kg /0.5% 25 mg/kg /0.05% No 10 10 3 4 10 TA1530 D3 Na 2 H 2 P 2 O 7 TA1535 Na 2 H 2 P 2 O 7 (+/ - S9mix) TA1536 TA1537 TA1538 in vivo TA1535 (+/ - S9mix) TA1537 TA1538 D4 TA1530 G46 D3 TA1535 (+/ - S9mix) TA1536 TA1537 TA1538 TA1535 (NaPO 3 ) 6 (+/ - S9mix) TA1536 TA1537 Na 2 H 2 P 2 O 7 Na 5 P 3 O 10 Na 5 P 3 O 10 Na 5 P 3 O 10 Na 5 P 3 O 10-24 -
( 1,500 mg ) / Na 2 H 2 P 2 O 7 Na 5 P 3 O 10 10 15 H 3 PO 4 2,0004,000 mg 14 2 H 3 PO 4 3,900 mg NaH 2 PO 4 5,0007,000 mg 15 NaH 2 PO 4 6,000 mg No 10-25 -
36 No / MgCl 2 LD 50 =1,0502,800 mg/kg 32 90 10 MgCl 2 00.10.52.5% 0 2.5% 623081,600 mg/kg / 0592991,531 mg/kg / 2.5% 2.5% 2.5% NOAEL 0.5%308 13 10 MgCl 2 00.30.61.252.55% 2.55% mg/kg /299 mg/kg / ( 06101,2202,690 5,41011,400 mg/kg / NOAELLOAEL 5,410 mg/kg 07701,5803,260/6,810 mg/kg / 6,81013,830 mg/kg / 2.5% ) 36 96 50 MgCl 2 00.52.0% 2% (00.753.0 g/kg / ) 2% 8 NOAEL 0.75 g/kg / 96 50 MgCl 2 00.52.0% 8 (00.753.0 g/kg / ) 6 15 22 MgCl 2 0200400 800 mg/kg / NOEL 800 mg/kg / 40-26 -
in vitro (+/ - S9mix) (+/ - S9mix) / TA92 TA94 TA98 TA100 TA1535 TA1537 TA98 TA100 TA1535 TA1537 WP2uvrA MgSO 4 100 mg/ 12 MgSO 4 5,000 µg/ 25 CHL MgSO 4 4.0 mg/ml 12 CHL/IU MgSO 4 1.255.0 mg/ml 25 (+/ - S9mix) TA1535 MgO 11 TA94 MgCl 2 100 mg/ml 13 (+/ - S9mix) TA98 TA100 TA2637 CHL MgCl 2 2.0 mg/ml TA97 MgCO 3 10 mg/ 14 (+/ - S9mix) TA98 TA100 TA102 CHL MgCO 3 1.0 mg/ml TA1537 TA1538 D4 TA1538 TA1535 TA1537 TA1538 D4 Mg(C 18 H 35 O 2 ) 2 No 11 JECFA ) (kg) (g//) (g/kg /) 0.02 3 150 0.4 20 50 NOAEL - 27 -