PBBs in animals

Most toxicity studies of PBBs in animals have involved oral exposure, and numerous effects have been documented including hepatic, renal, dermal/ocular, immunological, neurological, and developmental. 

Altered vitamin A homeostasis, primarily manifested as decreased hepatic storage of vitamin A, is another established effect of PBBs in animals. Vitamin A is essential for normal growth and cell differentiation, particularly differentiation of epithelial cells, and some PBB-induced epithelial lesions resemble those produced by vitamin A deficiency. Because it is the primary storage site for vitamin A, the liver has a major role in retinol metabolism. Esterification of dietary vitamin A, hydrolysis of stored vitamin A, mobilization and release into the blood of vitamin A bound to retinol-binding protein, and much of the synthesis of retinol-binding protein occurs in the liver. 

Limited information is available on lethal amounts of PBBs in animals. In general, dosing regimen and magnitude affect response. The lack of decreased survival in some studies does not necessarily indicate low toxicity because observation periods may not be sufficient to observe effects that develop slowly. 

Limited information is available regarding intermediate-duration dermal effects of PBBs in animals. A 10% chloroform solution of an unspecified commercial formulation of octabromobiphenyl did not induce bromacne when applied to the ear of rabbits for 30 days (Norris et al. 1975a). Only slight erythema and exfoliation was observed. Doses of 62 mg/kg of octabromobiphenyl mixture were not sensitizing when applied to the intact or abraded skin of guinea pigs over a 3-week period (Waritz et al. 1977). 

In vivo genotoxicity studies of PBBs in animals are summarized in Table 3-4. Administration of single oral doses between 50 and 1,000 mg of FireMaster FF-l/kg (purity not reported) by gavage in com oil to male and female B6C3F1 mice and male Fischer-344 rats did not induce unscheduled deoxyribonucleic acid (DNA) synthesis in hepatocytes (Mirsalis et al. 1985, 1989). However, doses 200 mg/kg significantly... 

No studies were located regarding quantitative absorption of PBBs in animals after inhalation exposure to PBBs. However, increased bromine concentrations were found in the liver and adipose tissue of rats exposed continuously to a commercial mixture of octabromobiphenyl for 15 weeks, suggesting that absorption had occurred (Waritz et al. 1977). 

A potential biomarker of exposure to PBBs is related to their effect on the thyroid gland. As discussed in Sections 3.2.2.2, Endocrine Effects, the thyroid gland is an unequivocal target of PBBs in animals, and evidence in humans is suggestive of a similar relationship. Effects in workers exposed to unspecified PBBs and/or decabromobiphenyl included increased scrum thyrotropin, low or borderline low serum T4, and increased thyroid antimicrosomal antibody titers (Bahn et al. 1980). A spectrum of thyroid effects has been... 

A review of the absorption, distribution and metabolism of PBBs in animals—mainly cattle and rodents—is already extant and will not be covered here (See DiCarlo et al, ref. 155). Suffice it to say that excretion rates of PBBs are exceedingly low, hence their biological half-lives long. Continued exposure leads to the build-up of PBBs in body fats. A major excretion route is via the lipid fraction of breast milk. 

Studies of PBBs in animals and humans have established their longterm accumulation in body lipids and very slow metabolism, hence prolonged storage in animals and man. While PBBs do cross the placental barrier, their transfer via nursing is considered to be of greater importance. 

Animal studies support he human evidence of neurobehavioral toxicity from prenatal exposure to low levels of lead. In an extensive review of the literature, Davis et al. (1990) discussed similarities between human effects and those in animals. The authors concluded that qualitatively "... the greatest similarities between human and animal effects involve cognitive and relatively complex behavioral processes such as learning." They further reported that quantitative relationships for PbB levels across species that cause developmental neurobehavioral effects are 10-15 pg/dL in children, <15 pg/dL in primates, and <20 pg/dL in rodents. 

Laboratory animals fed PBBs had body weight loss, skin disorders, and nervous system effects, and their livers, kidneys, thyroid glands, and immune systems were seriously injured. Some animals fed high amounts died. PBBs also caused birth defects in animals, but it is not known for sure whether PBBs make males or females infertile. Most of the effects in animals occurred after they ate large amounts of PBBs for short periods or smaller amounts for several weeks or months. In a lifetime study in rats and mice treated orally with PBBs at doses higher than those expected from environmental exposure, body weight loss and effects on the livers, kidneys, and thyroid glands were observed. A few studies tested animals exposed to PBBs by skin contact. These... 

It is not known whether the effects found in animals exposed to PBBs and PBDEs would also occur in people exposed in the same way. The amounts of PBBs and PBDEs that caused health effects in animals are much greater than levels of PBBs and PBDEs normally found in the environment or as yet found in people. Long-term exposure to these chemicals has a greater potential to cause health effects than short-term exposure to low levels because of their tendency to build up in your body over many years. More information on how PBBs and PBDEs can affect your health can be found in Chapter 3. 

FireMaster FF-1 after it was mistaken as a feed supplement and mixed with feed that was distributed within the state for several months before being discovered. Health problems in dairy cattle, reported in the fall of 1973, were the first signs that this episode occurred, but the accidental addition of PBBs to animal feed was not identified as the cause of the problem until the spring of 1974. 

Other effects of oral PBB exposure include decreased thyroid function, body weight loss, and liver cancer. Adverse hepatic as well as dermal and ocular effects have been observed in a limited number of dermal studies in animals. No significant adverse effects were observed in animal inhalation studies of PBBs, but only two studies have been conducted (one with octabromobiphenyl and one w ith decabromobiphenyl). 

Studies in animals, mostly intermediate-duration studies in rodents, indicate that a variety of immunological parameters such as spleen and thymus weights, antibody production, and lymphoproliferative responses can be affected by treatment with commercial PBB mixtures. The only chronic study found increased splenic hematopoiesis in mice, but no histological changes in the spleen, thymus, or lymph nodes of rats. It is... 

Unspecified signs of ocular irritation were observed in rats intermittently exposed to a high (5,000 mg/m ) dust concentration of decabromobiphenyl mixture for 4 weeks, but severity was not reported, and recovery was not assessed. Octabromobiphenyl and decabromobiphenyl mixtures caused mild eye irritation in rabbits when applied as a dry solid. Histopathological changes have not been observed in the eyes of rats or mice exposed orally to FireMaster FF-1 or FireMaster BP-6 in studies of acute, intermediate, or chronic duration. Xerophthalmia (extreme dryness of the conjunctiva) was reported in rats fed FireMaster BP-6 in an intermediate-duration study. Based on effects in animals, direct exposure to PBBs is likely to be irritating to human eyes. 

Based on the observations of adverse effects on reproduction in animals exposed to PBBs, the possibility that PBBs may cause reproductive harm in humans cannot be refuted and suggests that exposure of women to PBBs prior to and during the early phases of pregnancy may be of particular concern. 

Thyroid Effects. Limited information is available on thyroid effects in PBDE-exposed humans. There are suggestive occupational data as shown by effects that included increased serum FSH, low or borderline low serum T4, and increased thyroid antimicrosomal antibody titers in workers exposed to decaBDE and/or unspecified PBBs. There was no clear association between plasma levels of 2,2, 4,4-tetraBDE and thyroid hormone levels (free and total T3 and T4, TSH, free testosterone, follicle-stimulating hormone, lutenizing hormone, and prolactin) in men who consumed varying amounts of fatty fish from the Baltic Sea. Based on consistent evidence in animals, as summarized below, the thyroid is particularly sensitive to PBDEs and is a likely target of toxicity in exposed humans. 

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