Zabel E W, Walker M K, Hornung M W, Clayton M K, Peterson R E
Environmental Toxicology Center, University of Wisconsin, Madison 53706, USA.
Toxicol Appl Pharmacol. 1995 Oct;134(2):204-13. doi: 10.1006/taap.1995.1185.
Fish-specific toxic equivalency factors (TEFs), which relate the toxic potency of polyhalogenated aromatic hydrocarbons (PHAHs) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on the endpoint of early life stage mortality, have been used in assessing the risk to fish early life stage survival of complex mixtures of PHAHs in feral fish eggs. Use of TEFs assumes that PHAH congeners act additively. However, this has not been unequivocally determined. Isobolograms and a probit model were used to assess the validity of the additivity assumption by determining the significance of interactions between pairs of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners when injected into newly fertilized rainbow trout eggs in ratios bracketing those found in feral lake trout eggs from the Great Lakes. The majority of congener pairs tested acted additively in causing rainbow trout early life stage mortality: [1,2,3,7,8- pentachlorodibenzo-p-dioxin (1,2,3,7,8-PCDD)/TCDD]; [2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD]; (2,3,4,7,8-PCDF/TCDD), (2,3,7,8-tetrachlorodibenzofuran/2,3,4,7,8-PCDF); [3,3',4,4'-tetrachlorobiphenyl (PCB 77)/3,3',4,4',5-pentachlorobiphenyl (PCB 126)]; [2,3,3',4,4'-pentachlorobiphenyl (PCB 105)/TCDD]; (2,2',4,4',5,5'-hexachlorobiphenyl/TCDD); (PCB 105/PCB 126); and (2,3',4,4',5-pentachlorobiphenyl/PCB 126). The only pairs showing evidence of a statistically significant interaction that deviated from additivity were (TCDD/PCB 77) and (TCDD/PCB 126). Taken together, these results suggest that the use of fish-specific TEFs to determine TCDD equivalents contributed by individual congeners in a fish egg sample and then adding these TCDD equivalents to determine the total amount contributed by all congeners may not exactly predict the mortality risk posed to fish early life stages by the mixture of TCDD-like congeners in the eggs. However, the relatively small deviations from additivity in the rainbow trout sac fry mortality test (1- to 4-fold) are less than traditional uncertainty factors used in noncancer risk assessments (10-fold/factor) and are not sufficient to warrant a change away from the additivity assumption in assessing the risk to fish early life stage mortality posed by TCDD and related compounds in eggs.
鱼类特定毒性当量因子(TEFs)基于早期生命阶段死亡率这一终点,将多卤代芳烃(PHAHs)的毒性强度与2,3,7,8-四氯二苯并对二噁英(TCDD)相关联,已被用于评估野生鱼卵中PHAHs复杂混合物对鱼类早期生命阶段存活的风险。TEFs的使用假定PHAH同系物具有加和作用。然而,这一点尚未得到明确证实。通过确定多氯二苯并对二噁英(PCDD)、二苯并呋喃(PCDF)和联苯(PCB)同系物以接近五大湖野生湖鳟鱼卵中发现的比例注入新受精的虹鳟鱼卵时,各同系物对之间相互作用的显著性,使用等效线图和概率模型来评估加和性假设的有效性。测试的大多数同系物对在导致虹鳟鱼早期生命阶段死亡方面表现出加和作用:[1,2,3,7,8-五氯二苯并对二噁英(1,2,3,7,8-PCDD)/TCDD];[2,3,4,7,8-五氯二苯并呋喃(2,3,4,7,8-PCDF)/1,2,3,7,8-PCDD];(2,3,4,7,8-PCDF/TCDD),(2,3,7,8-四氯二苯并呋喃/2,3,4,7,8-PCDF);[3,3',4,4'-四氯联苯(PCB 77)/3,3',4,4',5-五氯联苯(PCB 126)];[2,3,3',4,4'-五氯联苯(PCB 105)/TCDD];(2,2',4,4',5,5'-六氯联苯/TCDD);(PCB 105/PCB 126);以及(2,3',4,4',5-五氯联苯/PCB 126)。唯一显示出偏离加和性且具有统计学显著相互作用证据的同系物对是(TCDD/PCB 77)和(TCDD/PCB 126)。总体而言,这些结果表明,使用鱼类特定的TEFs来确定鱼卵样本中各个同系物贡献的TCDD当量,然后将这些TCDD当量相加来确定所有同系物贡献的总量,可能无法准确预测鱼卵中类TCDD同系物混合物对鱼类早期生命阶段造成的死亡风险。然而,虹鳟鱼苗死亡率测试中与加和性的相对较小偏差(1至4倍)小于非癌症风险评估中使用的传统不确定性因子(10倍/因子),并且不足以保证在评估鱼卵中TCDD及相关化合物对鱼类早期生命阶段死亡风险时改变加和性假设。