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 μg 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 μg/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, hyperirritability, 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 nonsevere and reversible effect (i.e., bulging fontanel) and the interindividual variability in sensitivity.

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

Children and Adolescent Boys. There are 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 μg/day in young children to 15,000 μg/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 conservativism, the UL values for children and adolescents are extrapolated from those established for adults. Thus, the adult UL of 3,000 μg/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.