The UL for adolescent girls was adjusted on the basis of relative body weight as described in Chapter 3 with the use of reference weights from Chapter 1 (Table 1-1).

Data Selection. Data on liver abnormalities in humans were used to derive a UL. Because clear toxicity has been demonstrated in numerous studies at doses above 15,000 μg/day, only data involving doses less than 30,000 μg/day of vitamin A were included in Table 4-9. Data were thoroughly evaluated for other potential causes 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 cells, (2) no alcoholism, (3) no concomitant liver hepatitis, and (4) no hepatotoxic drug use. While hepatitis A and B status are known in most cases, testing for hepatitis C did not begin until the early 1990s and is unknown in most cases. Therefore, hepatitis C was not used as a criterion for exclusion.

Two case studies reported hypertrophy of Ito cells in a 63-year-old woman after vitamin A intake of 14,000 μg/day for 10 years (Minuk et al., 1988) and in a 36-year-old man who took about 15,000 μg/ day for 12 years (Zafrani et al., 1984). Neither of these reports appear to be confounded by hepatitis A or B viral infections or concomitant exposure to other hepatotoxic agents including alcohol. Reports of vitamin A-induced hepatotoxicity at doses less than 14,000 μg/day were found (Eaton, 1978; Hatoff et al., 1982; Kowalski et al., 1994; Oren and Ilan, 1992). However, as Table 4-9 shows,