defines a NOAEL as the highest intake at which no adverse effects have been observed) and identify the NOAEL for infants in this study based on the mean intake (for example, 44.4 µg or 1,775 IU/day) rather than the high end of the range. The NOAEL was rounded up to 45 µ g (1,800 IU)/day. Stearns (1968) subsequently commented that Fomon et al. (1966) did not study the infants long enough since the greatest differences in the Jeans and Stearns (1938) study appeared after 6 months. However, taken together, these papers support a NOAEL of 45 µg (1,800 IU)/day.

In two different surveys at two different time periods, the British Paediatric Association (BPA) (BPA, 1956, 1964) reported a marked decline in hypercalcemia in infants, from 7.2 cases per month in a 1953–1955 survey, to 3.0 cases per month in a 1960–1961 survey. This change occurred at the same time as new guidelines were introduced for fortification of food products with vitamin D. Data from BPA (1956) and Bransby et al. (1964) also show the estimated total vitamin D intake in infants at the seventy fifth percentile of 100 µg (4,000 IU)/day declining to a range of 18.1 to 33.6 µg (724 to 1,343 IU)/day between the two surveys.

Graham (1959) studied 38 infants aged 3 weeks to 11 months with hypercalcemia in Glasgow from 1951 to 1957. The data as reported offer no definitive proof of a relationship between vitamin D intake and hypercalcemia. However, Graham does report that the highest serum calcium value obtained, 4.65 mmol/liter (18.6 mg/dl), occurred in an infant with an estimated daily intake of 33 µg (1,320 IU)/day of vitamin D and that the infant made a complete recovery when vitamin D was omitted from the diet.

Taken together, these data indicate that excessive vitamin D intake is probably a risk factor for hypercalcemia in a few sensitive infants. However, these data are inadequate for quantitative risk assessment because the daily dosage is so uncertain. This is because of the inaccuracies of survey data, but also and more importantly, because sunlight exposure was not reported, and the level of fortification of food was probably not accurately determined, and was most likely underestimated.

Uncertainty and Uncertainty Factors. Given the insensitivity of the endpoint, the fact that sample sizes were small, and that little data exist about sensitivity at the tails of the distributions, an adjustment in the NOAEL or use of a UF of 1.8 is warranted.

Derivation of the UL. Based on a NOAEL of 45 µg (1,800 IU)/day for infants and a UF of 1.8, the UL for infants up to 1 year of age is set at 25 µg (1,000 IU)/day.



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