Brominated flame retardants are a novel group of global environmental contaminants. Within this group the polybrominated diphenyl ethers (PBDE) constitute one class of many that are found in electrical appliances, building materials, and textiles. PBDEs are persistent compounds that appear to have an environmental dispersion similar to that of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT). Levels of PBDEs are increasing in mother's milk while other organohalogens have decreased in concentration. We studied for developmental neurotoxic effects two polybrominated diphenyl ethers, 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) and 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99)--congeners that dominate in environmental and human samples--together with another frequently used brominated flame retardant, tetrabromo-bis-phenol-A (TBBPA). The compounds were given to 10-day-old NMRI male mice, as follows: PBDE 47, 0.7 mg (1.4 micromol), 10.5 mg (21.1 micromol)/kg body weight (bw); PBDE 99, 0.8 mg (1.4 micromol), 12.0 mg (21.1 micromol)/kg bw; TBBPA, 0.75 mg (1.4 micromol), 11.5 mg (21.1 micromol)/kg bw. Mice serving as controls received 10 mL/kg bw of the 20% fat emulsion vehicle in the same manner. The present study has shown that neonatal exposure to PBDE 99 and PBDE 47 can cause permanent aberrations in spontaneous behavior, evident in 2- and 4-month-old animals. This effect together with the habituation capability was more pronounced with increasing age, and the changes were dose-response related. Furthermore, neonatal exposure to PBDE 99 also affected learning and memory functions in adult animals. These are developmental defects that have been detected previously in connection with PCBs.

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This study shows that both a gamma-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-D-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.

Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), has been found to be increasing in the environment and in human milk. Previous studies have shown that lower brominated PBDEs, tetra-, penta-, and hexabrominated diphenyl ethers, can cause developmental neurotoxic effects. The present study shows that the highly brominated PBDE 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) can be absorbed during neonatal life and induce developmental neurotoxic effects in adult mice, effects that also worsen with age. These effects seem to be inducible only during a defined critical period of neonatal life. Neonatal Naval Medical Research Institute (NMRI) male mice were exposed on day 3 to 2.22 or 20.1 mg PBDE 209/kg body weight, on day 10 to 1.34, 13.4, or 20.1 mg PBDE 209/kg body weight, or on day 19 to 2.22 or 20.1 mg PBDE 209/kg body weight, or to [U-14C]-2,2',3,3',4,4',5,5',6,6'-decaBDE. The oral neonatal administration of [U-14C]PBDE 209 on day 3, 10, or 19 showed that the compound distributes throughout the body and increases in the brain, from 24 h after administration to 7 days after administration, in 3-day-old and 10-day-old mice. The spontaneous behavior tests, observed in 2-, 4-, and 6-month-old mice, showed that the effect only occurred in mice exposed on day 3 and that this effect worsened with age. We conclude that more attention should be focused on the highly brominated PBDEs as possible developmental neurotoxic agents.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.