Those questions are addressed in the following sections. Reproductive and developmental effects of beryllium are considered first, then other potentially relevant health end points.

REPRODUCTIVE AND DEVELOPMENTAL EFFECTS

Reproductive and developmental toxicity of beryllium compounds has been reviewed by EPA (1998b), the Agency for Toxic Substances and Disease Registry (ATSDR 2002), and the American Conference of Governmental Industrial Hygienists (ACGIH 2006). Animal studies have included oral and parenteral exposure but not inhalation exposure. Reproductive and developmental outcomes have not been examined in epidemiologic studies of beryllium workers, and only one study of reproductive and developmental outcomes in workers that included consideration of beryllium exposure was identified.

EPA’s (1998b) review focused on hazard assessment of environmentally relevant doses and concluded that “the potential of beryllium to induce developmental and/or reproductive effects has not been adequately assessed” (p. 50). It should be noted that many of the animal studies may have been conducted at doses that result in maternal toxicity and so might not have assessed effects directly on the fetus independently of effects on the mother.

The animal studies reviewed include a chronic dog-feeding study in which beryllium sulfate was mixed in the diet at three doses (from 0.023 to 1.3 mg/kg per day) and administered to males and females from before mating through weaning of pups (Morgareidge et al. 1976) and two studies previously reviewed by EPA (1991) in which beryllium compounds were administered parenterally to rats (Clary et al. 1975; Mathur et al. 1987). No adverse reproductive or developmental effects were reported in the dog study, and mixed results were reported in the rat studies.

EPA also noted that no reproductive or developmental effects were reported after paternal occupational exposure to beryllium by Savitz et al. (1989), who examined the effect of parents’ occupational exposure on risk of stillbirth, preterm delivery, and small-for-gestational-age infants in a case-control study that used data from the 1980 National Natality Survey and the 1980 National Fetal Mortality Survey. For stillbirths, case groups of 2,096 mothers and 3,170 fathers were examined for associations with 18 industrial or chemical categories. No maternal cases were listed for beryllium exposure, but 127 paternal cases associated with beryllium exposure were listed with an adjusted odds ratio (OR) of 1.0 (95% confidence interval [CI], 0.7-1.3). A similar analysis of preterm deliveries (363 mothers and 552 fathers) and small-for-gestational-age infants (218 mothers and 371 fathers) yielded no cases associated with maternal beryllium exposure. For paternal exposure, 23 cases of preterm delivery were associated with beryllium exposure (OR, 1.0; 95% CI, 0.5-2.0), and 16 cases of small-for-gestational-age infants were associated with beryllium exposure (OR, 0.9; 95% CI, 0.5-1.7). Thus, this study suggested no reproductive or developmental



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