V. STANDARDIZATION OF ACTIVITY 221 



necessary to check response curve interpretations by the use of reference 

 (positive control) groups, as descril)ed on the preceding page. 



V. Standardization of Activity 



CHARLES E. BILLS 



The present international standard for vitamin D, adopted by the World 

 Health Organization^ in 1949, is pure vitamin D3. The international unit 

 (I.U.) is defined as the vitamin D activity of 0.025 7 of the standard. The 

 U.S. Pharmacopeial unit is also now defined in terms of vitamin D3 and is 

 identical with the international unit. The former A.O.A.C. chick unit is 

 now replaced by the international chick unit, which also represents 0.025 

 7 of vitamin D3. Four of the A.O.A.C. units equal three international chick 

 units. A review of the development of the international unit is given by 

 Coward,- and a brief account of the recent changes is given by Nelson.^ 



The original international unit of vitamin D was defined^ "as the vita- 

 min D activity of 1 mg. of the international standard solution of irradiated 

 ergosterol." Parenthetically, and not as a part of the definition, it was noted 

 that "the international standard solution has been prepared to have such 

 potency that approximately 1 mg. thereof given daily to a rachitic rat for 

 eight successive days will produce a wide line of calcium deposits in the 

 metaphysis of the proximal ends of the tibiae and of the distal ends of the 

 radii." 



The original international standard solution was an olive oil solution of 

 ergosterol irradiation products, prepared under defined conditions and is- 

 sued from the National Institute for Medical Research, London. Solutions 

 of similar composition and potency had served, since 1927, as the Pharma- 

 ceutical Society's standard, and, since 1930, as the official standard of the 

 Medical Research Council of Great Britain.- • ^ At the second international 

 conference on vitamin standardization, 1934, the definition of the unit was 

 broadened to read, "the Vitamin D activity of 1 milligram of the interna- 

 tional standard solution of irradiated ergosterol, which has been found equal 

 to that of 0.025 microgram of crystalline vitamin D." Provision was made 



1 World Health Organization: Expert Committee on Biological Standardization, 



Chronicle World Health Org. 3, 147 (1949). 

 2K. H. Coward, J. Pharm. Pharmacol. 1, 737 (1949). 

 3 E. M. Nelson, J. Assoc. Offic. Agr. Chemists 32, 801 (1949). 

 ■•Report of the Conference on Vitamin Standards, No. C.H. 1055 (1). League of 



Nations, Geneva, 193L 

 6 K. H. Coward, F. J. Dyer, and B. G. E. Morgan, Analyst 57, 368 (1932). 



