Natarajan A T, Preston R J, Dellarco V, Ehrenberg L, Generoso W, Lewis S, Tates A D
Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Mutat Res. 1995 Aug;330(1-2):55-70. doi: 10.1016/0027-5107(95)00036-i.
A risk estimate of the heritable effects of ethylene oxide exposure, using the parallelogram approach, as suggested by Frits Sobels, is described. The approach is based on available data on the ethylene oxide-induced responses for the same genetic endpoint in somatic cells of both laboratory animals and humans, and for germ cell mutations in the same laboratory animal. Human germ cell effects are estimated. The available data sets for this approach were evaluated. We consider this as complementary to the genetic risk assessment carried out by U.S. EPA scientists, in which the risk from heritable (reciprocal) translocations induced by ethylene oxide was estimated. In the present study we restricted our assessment to dominant mutations. The sensitivity factor relating mouse to man was based on ethylene oxide-induced HPRT mutant frequencies in lymphocytes in vivo. From this comparison, it could be concluded that occupational exposure for 1 year to 1 ppm ethylene oxide would lead to a risk of a dominantly inherited disease in the offspring of 4 x 10(-4) above the background level. The uncertainty interval of this figure is quite large (0.6-28) x 10(-4). The values are compatible with the existing estimates of the corresponding risk from exposure to low LET radiation when the genotoxic potency ratio of ethylene oxide and radiation is considered. This risk estimation approach has allowed us to identify additional data that are required for a more complete risk estimation of the heritable effects of ethylene oxide, or indeed any mutagenic chemical.
本文描述了一种使用平行四边形方法对环氧乙烷暴露的遗传效应进行风险估计的方法，该方法由弗里茨·索贝斯提出。该方法基于实验室动物和人类体细胞中相同遗传终点的环氧乙烷诱导反应的现有数据，以及同一实验室动物中生殖细胞突变的数据。对人类生殖细胞效应进行了估计。对该方法可用的数据集进行了评估。我们认为这是对美国环境保护局科学家进行的遗传风险评估的补充，在该评估中，估计了环氧乙烷诱导的可遗传（相互）易位的风险。在本研究中，我们将评估限制在显性突变上。小鼠与人的敏感性因子基于体内淋巴细胞中环氧乙烷诱导的次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）突变频率。通过这种比较，可以得出结论，职业性接触1 ppm环氧乙烷1年会导致后代患显性遗传病的风险比背景水平高4×10⁻⁴。该数字的不确定区间相当大（0.6 - 28）×10⁻⁴。当考虑环氧乙烷与辐射的遗传毒性效力比时，这些值与现有对低传能线密度辐射相应风险的估计值相符。这种风险估计方法使我们能够确定进行更完整的环氧乙烷遗传效应风险估计或任何诱变化学品风险估计所需的其他数据。
