All Other Adults Ages 19 Years and Older, Excluding Women of Childbearing Age
Data Selection. Data on liver abnormalities in humans were used to derive a UL. Bccausc clcar toxicity has been demonstrated in numerous studies at doses above 15,000 jig/day, only data involving doses less than 30,000 jig/day of vitamin A were included in Table 4-9. Data were thoroughly evaluated for other potential causcs of liver abnormalities. The following criteria for selecting the data sets were used: (1) data must show grossly elevated liver vitamin A levels or hypertrophy of Ito cclls, (2) no alcoholism, (3) no concomitant liver hepatitis, and (4) no hcpatotoxic drug use. While hepatitis A and B status arc known in most eases, testing for hepatitis C did not begin until the early 1990s and is unknown in most eases. Therefore, hepatitis C was not used as a criterion for exclusion.
Two ease studies reported hypertrophy of Ito cclls in a 63-ycar-old woman after vitamin A intake of 14,000 jig/day for 10 years (Minuk et al., 1988) and in a 36-ycar-old man who took about 15,000 ytg/ day for 12 years (Zafrani et al., 1984). Neither of these reports appear to be confoundcd by hepatitis A or B viral infections or concomitant exposure to other hcpatotoxic agents including alcohol. Reports of vitamin A-induccd hcpatotoxicity at doses less than 14,000 ytg/day were found (Eaton, 1978; Hatoff ct al., 1982; Kowalski et al., 1994; Orcn and Ilan, 1992). However, as Table 4-9 shows,
these studies fail to provide information on other predisposing or confounding factors such as alcohol intake, drugs and medications used, and history of viral hepatitis infection.
Uncertainty Assessment. A UF of 5.0 was selected to account for the severe, irreversible nature of the adverse effect, extrapolation from a lowcst-obscrvcd-advcrsc-cffcct level (LOAFL) to a NO AFX, and intcrindividual variation in sensitivity.
Derivation of a UL. Hcpatotoxicity was reported at vitamin A supplement doses of 14,000 yig/day. A LOAFX of 14,000 ytg/day was divided by a UF of 5 to obtain a UL after rounding of 3,000 ytg/day for adults other than women of reproductive age. This UL is the same as that set for women of reproductive age, given that the UL is defined as the highest level of daily nutrient intake likely to pose no risk of adverse health effects to almost all of the general population.
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