PBDEs human toxicity

Both animal model and in vitro studies suggest adverse developmental, reproductive, and neurotoxic as well as endocrine disruptive effects associated with exposure to PBDEs. Evidences for ElXI activity of PBDEs are based primarily on animal model studies (Van der Ven et al., 2008). Mice and rat studies on deca-DBE at a dose level of about 5 mg/kg bw/day or above resulted in B-cell activation and a reduced number of natural killer (NK) cells in the offspring (Teshima et al., 2008). The limited human toxicity data reported are summarized in Table 7.10. 

PBBs and PBDEs). US Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry,... 

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. 

Developmental Effects. Oral developmental toxicity studies of deca-, octa-, and pentaBDE have shown no evidence of teratogenicity in animals. Gestational exposure to a high (1,000 mg/kg/day) but maternally nontoxic dose of decaBDE was fetotoxic in rats as shown by subcutaneous edema and delayed skull bone ossification. Commercial mixtures of octaBDE caused skeletal ossification variations in rats and rabbits at maternally toxic levels and other indications of fetotoxicity at lower doses. Effects of gestational exposure to octaBDE included minimally increased postimplantation loss in rats at >10 mg/kg/day, increased resorptions in rats at 25 mg/kg/day, and increased skeletal variations in rabbits at 15 mg/kg/day and rats at 50 mg/kg/day. No evidence of fetotoxicity was found in the only available study of pentaBDE in rats at maternally toxic doses < 200 mg/kg/day. No studies are available on developmental effects of PBDEs in humans. Based on the evidence in animals, PBDEs are unlikely to cause developmental toxicity at expected levels of exposure. 

Due to tlie likelihoods that (1) multiple mechanisms (Ah-receptor-dependent mechanisms, Ah-receptor independent mechanisms, or both) may be involved in health effects induced by PBBs/PBDEs, (2) different PBB/PBDE congeners may produce effects by different mechanisms, and (3) humans are exposed to complex mixtures of interacting PBBs/PBDEs with differing biological activities, as well as to the lack of a suitable approach for quantitatively evaluating joint toxic action from concurrent exposures to PBBs, PBDEs, PCBs, CDDs, and/or CDFs in tlie environment, data from commercial PBB and PBDE mixtures are used to develop MRLs for assessing health risks from environmental exposures to PBBs or PBDEs. 

Zhou et al. 2001, 2002). The available data indicate that the thyroid is a particularly sensitive target of acute oral exposure and justify using thyroid effects as the basis for an acute oral MRL, but acute effects of PBDEs on the liver are not as well characterized as thyroid effects. Other studies indicate that immunosuppression and neurobehavior are important and potentially critical health end points for acute exposure to PBDEs that need to be further investigated (see discussions of data needs for Immunotoxicity and Neurotoxicity). Studies in other species would help to clearly establish the most sensitive target and species for acute exposure, as well as which animal toxicity data are the most relevant to humans and useful for assessing acute health risks. 

This chapter focuses on the 12 most toxic POPs subject to control of the Stockholm Convention. It is recognized that there are other POPs which have been demonstrated to elicit adverse effects of toxicological significance on human health and the environment, for which international agreement has yet to be reached on their inclusion in the Convention list. Indeed, five new POPs candidates (hexabromobiphenyl (6-PBB), pent-abromodiphenyl ether (PBDE), perfluorooctane sulfonate (PFOS), chlordecone and lindane) were proposed and considered at the First Meeting of the POPs Review Committee of the Stockholm Convention in November 2005 (UNEP, 2005). The challenge is for the local scientific... 

The toxicity, bioaccumulative potential, and ecological impact of organohalogenated substances such as polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), polychlorinated d iben zo -pa ra - diox i n s (PCDDs), or polybrominated diphenylethers (PBDEs) have been extensively reviewed.95 98 All are referred to as persistent organic pollutants (POPs), that is, chemical substances that remain in the environment, bioaccumulate through the food chain, and pose a risk to human health and the environment. The international community is calling for action to reduce and then eliminate the production or formation of these substances and to monitor their emission. In this case, the detectability obtainable by analytical methods should be very low, since the limits established for these residues are in the ng per liter range. 

The most frequently used BFRs are polybrominated diphenylethers (PBDEs), tetrabromobisphenol A (TBBPA), and hexabromocyclododecane (HBCD). The use of FRs has been growing rapidly in recent years. BFRs are the most often used FRs, and their market is still growing. However, the estimated annual use of OPFRs in Western Europe was almost twice that of all BFRs combined. Many FRs have been banned for use because of their potential toxicity, environmental occurrence, and accumulation in human tissue. FRs taken off the market are likely to be replaced by others. Although the REACH (registration, evaluation, authorization and restriction of chemicals) regulatory system has been introduced in Europe to improve protection of human health and the environment, it is still necessary to monitor FRs in environmental samples [84, 88]. 

The structural range of industrially important representatives of these groups is enormous, and includes chlorobenzenes (solvents), to PCBs (hydraulic and insulating fluids), and polybrominated biphenyls (PBBs) and polybrominated diphenyl ethers (PBDE) ethers (flame retardants). There is widespread concern over both the persistence and the potential toxicity of all these compounds, so that sites contaminated during their production represent a threat both to the environment and to human health. Comments have already been made in Chapter 6, Section 6.5.1.1 on the pathways for the aerobic bacterial degradation of chlorobenzenes and chlorobiphenyls. 

Several countries have been given restrictions on the use of compounds because of potential toxic effects in humans. In the European Community, the use of tris(2,3-dibromopropyl) phosphate (EC Directive 76/769/EEC) and tris(l-aziridinyl)phosphine oxide (EC Directive 83/264/EEC) in textiles has been banned. In 1977, the U.S. Consumer Product Safety Commission banned the use of tris(2,3-dibromopropyl) phosphate in children s clothing (ICPS, 1995). The European Community has also banned the use of PBBs in textiles (EC Directive 83/264/EEC). Several countries have either taken or proposed regulatory actions on PBBs. In addition, controls on the emissions of dioxins and furans from municipal solid waste incinerators have been implemented in the United Kingdom under the Environmental Protection Act (1990). Germany has developed rules for the maximum content of selected 2,3,7, and 8 substituted polychlorinated dibenzo-pura-dioxins and dibenzofurans in products. Recently, the European Commission has issued a proposal to ban the production and use of PentaBDE. In U.S. A., on the other hand, there are currently no regulations on PBDE production or use. PBBs have not been used widely in Europe and also in U.S.A. the production of the main mixture, hexabromobiphenyl (Firemaster BP-6), ceased in 1974, after the Michigan disaster. ... 

Polybrominated diphenyl ethers (PBDEs), mainly used as flame-retardants, have a total of 209 possible congeners. These compounds are being released into the environment more frequently because of their increased use in plastic materials and synthetic fibers. Environmentally significant concentrations have been reported in air, water, soil, sediment, and sewage samples, in aquatic and terrestrial organisms [45], and in human breast milk [46]. Little is known about their toxicity on organisms in the environment however, there is indication that they are endocrine disrupters capable of affecting the thyroid system [47]. 

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