Biesemeier John A, Beck Melissa J, Silberberg Hanna, Myers Nicole R, Ariano John M, Radovsky Ann, Freshwater Les, Sved Daniel W, Jacobi Sylvia, Stump Donald G, Hardy Marcia L, Stedeford Todd
Chemtura Corporation, West Lafayette, Indiana 47906, USA.
Birth Defects Res B Dev Reprod Toxicol. 2011 Feb;92(1):17-35. doi: 10.1002/bdrb.20280. Epub 2011 Jan 31.
Decabromodiphenyl ether (DecaBDE; CASRN 1163-19-5) is a flame retardant used in a variety of manufactured products. A single oral dose of 20.1 mg/kg administered to mice on postnatal day 3 has been reported to alter motor activity at 2, 4, and 6 months of age.
To further evaluate these results, a developmental neurotoxicity study was conducted in the most commonly used species for studies of this type, the rat, according to international validated testing guidelines and Good Laboratory Practice Standards. DecaBDE was administered orally via gavage in corn oil to dams from gestation day 6 to weaning at doses of 0, 1, 10, 100, or 1,000 mg/kg/day. Standard measures of growth, development, and neurological endpoints were evaluated in the offspring. Motor activity was assessed at 2 months of age. Additional motor activity assessments were conducted at 4 and 6 months of age. Neuropathology and morphometry evaluations of the offspring were performed at weaning and adulthood.
No treatment-related neurobehavioral changes were observed in detailed clinical observations, startle response, or learning and memory tests. No test substance-related changes were noted in motor activity assessments performed at 2, 4, or 6 months of age. Finally, no treatment-related neuropathological or morphometric alterations were found.
Under the conditions of this study, the no-observed-adverse-effect level for developmental neurotoxicity of DecaBDE was 1,000 mg/kg/day, the highest dose tested.
十溴二苯醚（DecaBDE；化学物质登记号1163 - 19 - 5）是一种用于多种制成品的阻燃剂。据报道，在出生后第3天给小鼠单次口服20.1毫克/千克的剂量，会在其2、4和6个月大时改变运动活性。
为进一步评估这些结果，根据国际认可的测试指南和良好实验室规范标准，在这类研究中最常用的物种大鼠身上进行了一项发育神经毒性研究。从妊娠第6天至断奶，以0、1、10、100或1000毫克/千克/天的剂量，通过灌胃将十溴二苯醚经玉米油给予母鼠。对后代的生长、发育和神经学终点的标准指标进行了评估。在2个月大时评估运动活性。在4个月和6个月大时进行了额外的运动活性评估。在断奶和成年期对后代进行了神经病理学和形态学评估。
在详细的临床观察、惊吓反应或学习与记忆测试中，未观察到与治疗相关的神经行为变化。在2、4或6个月大时进行的运动活性评估中，未发现与受试物质相关的变化。最后，未发现与治疗相关的神经病理学或形态学改变。
在本研究条件下，十溴二苯醚发育神经毒性的未观察到有害作用水平为1000毫克/千克/天，即测试的最高剂量。
