Stunted growth, increased mortality, and liver tumors in offspring of polybrominated biphenyl (PBB) dosed Sherman rats

Abstract

Firemaster FF-1, a polybrominated biphenyl (PBB) mixture, was dissolved in corn oil and given as a dose of 200 mg/kg body weight to Sherman rats on d 7 and 14 of pregnancy. Control rats received equivalent doses of corn oil alone. Selected pups and all dams were killed 1 mo after pups were weaned. A total of 50 male and 50 female offspring per group were followed until they were 2 yr old. The livers of offspring killed at the ages of 2 mo and 2 yr had PBB levels of 2,4 (SD 1.2) and 0.8 (SD 0.65) mg/kg for females and 3.0 (SD 1.6) and 0.6 (SD 0.37) mg/kg for males, respectively. The incidence of hepatocellular carcinomas was 3/51 (5.9%) and 4/41 (9.6%) after 2 yr in females and males, respectively. Hepatocellular carcinomas were not observed among the controls. Neoplastic (hyperplastic) nodules of the liver were present in 9/51 (17.6%) and 2/41 (4.9%) of exposed females and males, respectively, whereas only 2/48 (4.2%) of control females and no control males had neoplastic (hyperplastic) nodules. Body weights were lower in PBB-exposed rats at ages 1, 6, 12, and 24 mo. Survival rates from birth to weaning were lower in PBB-exposed pups (89%) than in controls (98%). Mortality was two times higher in PBB-exposed males (64%) than in control males (32%) after 2 yr. Transplacental PBB exposure and exposure through milk resulted in PBB body burdens in the offspring still measurable at the end of their lifespan. These offspring had increased mortality rates and lower body weights than controls, and they developed hepatocellular carcinomas.

Laboratory and Human Studies on Polychlorinated Biphenyls (PCBs) and Related Compounds

“…In addition to the hepatocellular carcinomas, neoplastic nodules were observed in 17.6% exposed females and in 4.9% exposed male rats. All exposed rats gained less weight, and the lifespan of the male rats appeared reduced in that many male rats died earlier than the controls (30). It is therefore possible to induce hepatocellular carcinomas in offspring of dams treated with PBB.…”

“…In a recent study, dams of Sherman strain rats were given two doses of 200 mg/kg of PBB by gavage during pregnancy. The offspring that were also nursed by the treated dams still had measurable PBB body burdens at the end of their life span (see also carcinogenesis) (30) (34) exposed female Sherman rats to dietary levels of 100 mg/kg Aroclor 1260 and found 26 hepatocellular carcinomas in 184 exposed rats, whereas only one of 173 controls had a hepatocellular carcinoma. In addition, many exposed rats had neoplastic nodules.…”

Scientific Opinion on Polybrominated Biphenyls (PBBs) in Food

“…In rats exposed to FireMaster FF-1 (200 mg/kg b.w.) by gavage on GD7 and GD14, decreased pup survival, decreased body weight gain in offspring, and increased mortality in offspring were observed over 24 month after the exposure (Groce and Kimbrough, 1984). In seven rhesus female monkeys that were fed 0.012 mg/kg b.w.…”

Polychlorinated Biphenyls and Polybrominated Biphenyls

“…In a second study, groups of 30 female rats were given Firemaster FF-1 at a dose of 100 mg/kg bw by gavage twice per week for two 3-week periods separated by approximately 10 weeks (total of 12 doses). After 24 months observation, the incidences of hepatocellular (trabecular) carcinoma and hepatic neoplastic nodules were significantly increased -17 out of Rat, Sherman (M, F) 24 mo Groce & Kimbrough (1984), EFSA 28 (61%) versus 0 out of 25 (controls), and 24 out of 28 (82%) versus 1 out of 25 (4%; controls). In a third study, groups of 16 female rats were given Firemaster FF-1 as a single dose at 200 mg/kg bw by gavage.…”

“…In a study in pregnant Sherman rats given Firemaster FF-1 at an oral dose of 200 mg/kg bw on days 7 and 14 of gestation, the incidences of neoplastic nodules and hepatocellular carcinoma were slightly increased (not significantly) in male and female offspring over the 24 months after treatment (Groce & Kimbrough, 1984).…”