UL for Women 51 years3000 yigday of preformed vitamin A

Infants, Children, and Adolescent Boys

Data Selection. Case reports of hypcrvitaminosis A in infants were used to identify a LOAFL and derive a UL. Data were not available to identify a NOAFL.

Identification of a LOAEL. A LOAFX of 6,460 yig/day of vitamin A (which was rounded to 6,000 yig/day) was identified by averaging the lowest doses of four case reports (Pcrsson ct al., 1965). Four cases of hypcrvitaminosis A occurred after doses of 5,500 to 6,750 yig/day of vitamin A for 1 to 3 months (Table 4-10). The age of onset of symptoms ranged from 2.5 to 5.5 months and included anorexia, hypcrirritability, occipital edema, pronounced craniotabcs, bulging fontanels, increased intracranial pressure, and skin lesions

144 DTETARY REFERENCE INTAKES

and desquamation. The lowest dose associated with a bulging fontanel involved a 4-month-old girl given a daily dose of 24 drops of AD-vimin (about 5,500 jig of vitamin A) for 3 months. Her fontanels bulged 0.5 centimeters above the plane of the skull. The other three cases involved a dose of 6,750 ng/day of vitamin A for 1 to 2.5 months. Increased intracranial pressure and bulging fontanels were observed in these cases as well. Other effects observed at the higher dose included anorexia, hypcrirritability, occipital edema, pronounced craniotabes, skin lesions, skin desquamation, epiphyseal line changes, and cortical hyperostosis on x-rays.

Uncertainty Assessment. A UF of 10 was selected to account for the uncertainty of extrapolating a LOAEL to a NOAEL for a nonscvcrc and reversible effect (i.e., bulging fontanel) and the interindividual variability in sensitivity.

Derivation of a UL. The LOAEL of 6,000 jig/day was divided by a UF of 10 to calculate a UL of 600 jig/day of preformed vitamin A for infants.

Children and Adolescent Boys. There arc limited case report data of hypervitaminosis A (e.g., bulging anterior fontanels, increased intracranial pressure, hair loss, increased suture markings on the skull, and periosteal new bone formation) in children and adolescents after doses ranging from 7,000 jig/day in young children to 15,000 yig/day in older children and adolescents (Farris and Erdman, 1982; Siegel and Spackman, 1972; Smith and Goodman, 1976). Given the dearth of information and the need for conscrvativism, the UL values for children and adolescents arc extrapolated from those established for adults. Thus, the adult UL of 3,000 yig/day of preformed vitamin A was adjusted for children and adolescents on the basis of relative body weight as described in Chapter 2 with use of reference weights from Chapter 1 (Table 1-1). Values have been rounded.

Vitamin A UL Summary, Infants, Children, and Adolescent Boys

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