PBBs humans

The principal source of pollution by polybrominated biphenyls (PBBs) has been the commercial mixture Firemaster, which was produced in the United States between 1970 and 1974. Production was discontinued in 1974 following a severe pollution incident in Michigan, when Firemaster was accidentally mixed with cattle feed on a farm. In due course, PBBs entered the human food chain via contaminated animal products. Substantial residues were found in humans from the area, and were snbse-quently found to be highly persistent. 

Firemaster is a stable solid, resembling a PCB mixture in its lipophilicity, chemical and thermal stability, and low vapor pressure. Firemaster contains some 80 ont of a possible 209 PBB congeners, but just two of them— 2,2, 4,4, 5,5-hexabromobiphenyl and 2,2, 3,4,4, 5,5, heptabromobiphenyl—account for around 85% of the commercial product (Environmental Health Criteria 152). These two componnds were fonnd to be very slowly eliminated by humans exposed to them during the Michigan incident. A half-life of abont 69 weeks was estimated for 2,4,5,2,4, 5 -HBB. 

PBB mixtures have been used as fire retardants. Many of their constituent congeners are highly persistent, and there was a major environmental accident in the United States in which farm animals and humans became heavily contaminated by them. 

Effects in Humans Based on Blood Lead (PbB) Levels... 

As discussed in the introduction to Section 2.2, the bulk of the human data on the health effects of lead are expressed in terms of internal exposure, or PbB levels, rather than external exposure levels (i.e., mg/m3 or mg/kg/day). For the general population, exposure to lead occurs primarily via the oral route with some contribution from the inhalation route, whereas occupational exposure is primarily by inhalation with some oral. Therefore, it is difficult to distinguish specific routes and levels of exposure. For this reason, the human health effects data for lead will be presented in terms of PbB levels in this section. Health effects associated with human exposures to lead and internal lead doses are shown in Table 2-1. 

A major limitation inherent in a good portion of the human health effects studies is that exposure durations, and sometimes PbB levels, are not specified. However, many of the studies deficient in experimental detail still provide useful information, and they will be discussed in this section even if they are not recorded in Table 2-1. 

Respiratory Effects. The only information located regarding respiratory effects in humans associated with lead exposure was a case report of a 41-year-old man who was exposed to lead for 6 years while removing old lead-based paint from a bridge. At the time of the initial assessment, his PbB level was 87 pg/dL, and he complained of mild dyspnea for the last 2-3 years. No abnormalities in respiratory function were seen at clinical examination, so it is not possible to conclude that his respiratory symptoms were related to exposure to lead (Pollock and Ibels 1986). 

Cardiovascular Effects. There is currently considerable scientific debate as to whether there is a causal relationship between lead exposure and hypertension. Another area of controversy is whether African Americans are more susceptible to the cardiovascular effects of lead than are whites or Hispanics. The evidence from both occupational studies and large-scale general population studies (i.e., National Health and Nutrition Examination Survey [NHANES II], British Regional Heart Study [BRHS]) is not sufficient to conclude that such a causal relationship exists between PbB levels and increases in blood pressure. The database on lead-induced effects on cardiovascular function in humans will be discussed by presenting a summary of several representative occupational studies followed by a discussion of the findings from the large-scale general population studies. 

Renal Effects. Ingestion of drinking water containing lead was found to be associated with evidence of renal insufficiency in humans (Campbell et al. 1977). Lead concentrations in drinking water were compared to PbB concentrations in 283 residents who ingested this water for a mean of 21.5 years. A highly significant correlation was found for these two parameters. In addition, elevated PbB concentrations were associated with renal insufficiency, reflected as raised serum urea concentrations and hyperuricemia. No renal biopsies were performed. 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

Transplacental transfer of lead in humans has been demonstrated in a number of studies, and lead has been identified in umbilical cord blood. In the work of Bellinger et al. (1987a), the mean lead concentration in umbilical cord blood from a sample size of 11,000 women was 6.6 3.2 pg/dL. In a study of 236 pregnant women in Glasgow, Scotland, the geometric mean PbB levels were 14 pg/dL for... 

Renal Effects. Exposure to lead that results in PbB ranging from approximately 60 to >100 pg/dL has been associated with nephropathy in some studies of lead-exposed workers (e.g., Chia et al. 1995a). The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, few or no nuclear inclusion bodies,... 

Neurological Effects. The data on neurobehavioral toxicity of exposure to lead suggest that children are more sensitive, as indicated by responses at lower PbB levels, than are adult humans, and that animals are affected at roughly the same PbB levels as are humans. 

In humans, encephalopathy can occur at PbB levels as low as 100-120 pg/dL in some adults (Kehoe 1961a, 1961b, 1961c Smith et al. 1938) and at PbB levels as low as 80-100 pg/dL in some children (EPA 1986a NAS 1972). This condition can result in death or in permanent cognitive impairment, particularly in children. Furthermore, children with high PbB levels (>80-100 pg/dL) and symptoms of... 

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. 

The low concentrations of lead in plasma, relative to red blood cells, has made it extremely difficult to accurately measure plasma lead concentrations in humans, particularly at low PbB concentrations (i.e., less than 20 pg/dL). However, more recent measurements have been achieved with inductively coupled mass spectrometry (ICP-MS), which has a higher analytical sensitivity than earlier atomic absorption spectrometry methods. Using this analytical technique, recent studies have shown that plasma lead concentrations may correlate more strongly with bone lead levels than do PbB concentrations (Cake et al. 1996 Hemandez-Avila et al. 1998). The above studies were conducted in adults, similar studies of children have not been reported. 

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