Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Arch Toxicol. 2020 Mar;94(3):717-724. doi: 10.1007/s00204-020-02700-x. Epub 2020 Mar 13.
Because of the high pK of boric acid, inorganic borates, when taken up by the human or animal organism, exist in the body almost exclusively in the form of non-dissociated boric acid. Therefore, the variety of inorganic boron compounds is commonly addressed in the toxicological literature as "boron" (B). There is a discussion concerning categorisation of inorganic boron compounds as reproductive toxins. Boron treatment of rats, mice and dogs was dose-dependently associated with testicular toxicity, characterised by inhibited spermiation at lower dose levels and by reduction of epididymal sperm counts at higher dose levels. The NOAEL for such fertility effects of boric acid in male rats (oral feeding, Sprague Dawley strain) was evaluated to be 17.5 mg B/kg bw per day. As far as developmental toxicity is concerned, oral dosing of 9.6 mg B/kg bw daily to female pregnant Sprague Dawley rats remained without effects, with foetal skeletal effects observed at higher doses. Therefore, 9.6 mg B/kg bw (oral dosing) was evaluated as NOAEL for developmental effects of boric acid. The blood level in rats, equivalent to this NOAEL, is 1270 ng B/g. As far as B-exposed humans are concerned, field studies on the effect of boron on human reproduction are possible only in a few boron-rich geographical areas. Published field studies were conducted in China's Liaoning province, the Argentinian Andes and Western Anatolia/Turkey. Particularly relevant are studies on occupationally B-exposed groups, because the potential exposure to boron is much higher in occupational compared to environmental settings. Comparison of estimated daily B exposure levels in humans and actually measured B blood levels confirms the preference of biomonitoring for exposure assessment in environmental and occupational studies. A boron blood level scaling shows that the levels of high occupational B exposures reported in China and in Turkey are compatible. Compared to the experimental B blood levels at boron-related NOAELs for male fertility and for developmental toxicity in rats, the human blood level means of the highest occupational exposure groups in China and in Turkey are lower by factors of > 4 and > 2, respectively. Basically, concentrations of B within the body that exert reproductive toxicity in humans are not reached under the conditions of human normal handling and use, including conditions of extreme occupational exposures. In consequence, all relevant results of studies into human reproductive toxicity of B are basically negative. Considering the effective doses, there is no scientific contradiction between experimental and human results of B reproductive toxicity.
由于硼酸的高 pK 值，无机硼酸盐在被人体或动物吸收后，几乎完全以非解离硼酸的形式存在于体内。因此，毒理学文献中通常将各种无机硼化合物称为“硼”（B）。关于将无机硼化合物归类为生殖毒素存在一些讨论。硼对大鼠、小鼠和狗的处理与睾丸毒性有关，其特征是较低剂量水平下的精子发生受到抑制，较高剂量水平下附睾精子计数减少。雄性大鼠（口服喂养，斯普拉格-道利）硼酸此类生育效应的无观察不良效应水平（NOAEL）评估为 17.5mg B/kg bw/天。就发育毒性而言，每日口服 9.6mg B/kg bw 对怀孕的雌性斯普拉格-道利大鼠没有影响，但在较高剂量下观察到胎儿骨骼效应。因此，9.6mg B/kg bw（口服剂量）被评估为硼酸发育效应的无观察不良效应水平。大鼠血液中相当于该无观察不良效应水平的硼浓度为 1270ng B/g。就暴露于硼的人类而言，只有在少数硼丰富的地理区域才能进行硼对人类生殖影响的现场研究。已发表的现场研究在中国辽宁省、阿根廷安第斯山脉和西安纳托利亚/土耳其进行。特别相关的是对职业性硼暴露组的研究，因为与环境环境相比，职业环境中硼的潜在暴露量要高得多。比较人类每日硼暴露水平的估计值和实际测量的硼血水平，证实了生物监测在环境和职业研究中用于暴露评估的偏好。硼血水平比例表明，中国和土耳其报告的高职业硼暴露水平是一致的。与大鼠硼相关的无观察不良效应水平的雄性生育力和发育毒性的实验硼血水平相比，中国和土耳其最高职业暴露组的人类血液水平平均值分别低 4 倍和 2 倍以上。基本上，在人类正常处理和使用条件下，包括极端职业暴露条件下，不会达到对人体生殖毒性的硼体内浓度。因此，硼对人类生殖毒性的所有相关研究结果基本上都是阴性的。考虑到有效剂量，硼的实验和人体生殖毒性结果之间没有科学矛盾。
