Potential tolerance against bromobenzene-induced acute hepatotoxicity due to prior subchronic exposure

Groups of adult male Sprague-Dawley rats were treated i.p. with 0, 0.3 and 0.5 mmole bromobenzene (BB)/kg per day in corn oil, 5 days a week for 4 weeks. Thereafter, one half of each of these groups was treated i. p. with a single acute toxic dose of 2.5 mmole BB/kg. Urines were then collected for 24 h and the animals were then sacrificed. The hepatotoxicity induced by an acute dose of BB was significantly reduced due to prior subchronic exposure to BB at 0.5 mmol/kg, but not so at 0.3 mmol/kg. These data indicate a potential tolerance against acute hepatotoxicity of BB due to prior subchronic exposure. A significant increase in the urinary excretion of thioethers or mercapturic acids of BB combined with a significant increase in the urinary level ofp-bromocatechol due to prior subchronic treatment with 0.5 mmol BB/kg relative to those due to acute treatment alone was observed. Thus enhanced bromobenzene metabolism could partly explain such potential tolerance against its acute hepatotoxicity. Such protection may also be related to certain cellular events which might occur subsequent to metabolic activation of BB.     

The use of a safety factor in setting health based permissible levels for occupational exposure

Summary When adequate human observations are not or scarcely available, permissible levels for occupational exposure have to be extrapolated from animal experiments. Taking into account experimental conditions, e. g., duration of exposure ( 3 months), animal species, knowledge of no- (adverse-) effect level or minim al-(adverse-) level, presence of data on human observations, the authors worked out a procedure for extrapolation. This procedure should only be applied for systemic non-carcinogenic effects. The proposed procedure is to be regarded as tentative and as suggestion for international discussion.The evaluation starts with a safety factor = 10 for extrapolation from dose/kg b. w. in long-term animal experiments to exposure of adult workers (40 h/wk); this factor corresponds to a safety factor = 3–10 for extrapolation from doses presented as concentrations in air. If long-term experimental exposure is 24 h daily, the safety factor can be lowered to the minimum value of 1. If only short-term exposure studies are available, the safety factor may have to be increased to a maximum of 400.     

Exposure to 1-bromopropane causes ovarian dysfunction in rats.

Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.     

Respiratory exposure to diesel exhaust particles decreases the spleen IgM response to a T cell-dependent antigen in female B6C3F1 mice.

We investigated the systemic immunotoxic potential of respiratory exposure to diesel exhaust particles (DEP) in this study. Female B6C3F1 mice (approximately 8 weeks old) were exposed to increasing concentrations of DEP intratracheally, 3 times every two weeks, and sacrificed 2 or 4 weeks after the first exposure. The systemic toxicity and immune status in mice were evaluated. Mice exposed to DEP (1 to 15 mg/kg) showed no significant changes in body, spleen, or liver weights. Lung weights were increased in the mice exposed to 15 mg/kg DEP for 2 or 4 weeks. Except for a decreased platelet count, no significant alterations occurred in hematological parameters following DEP exposure. The number of splenic anti-sheep red blood cell (sRBC) IgM antibody-forming cells (AFC) decreased following DEP exposure for 2 weeks. This effect was less severe following 4 weeks of exposure and was only evident in the high dose group. Exposure to DEP also resulted in a significant decrease in the absolute numbers and the percentages of total spleen cells for total, CD4(+), and CD8(+) T cells, while the numbers of B cells and total nucleated cells in spleen were not significantly changed. The proliferative response of splenocytes to the T-cell mitogen, concanavalin A (ConA), as well as their production of IL-2 and IFN-gamma, was decreased dose-dependently following exposure of mice to DEP for 2 weeks, whereas proliferation was not changed in response to anti-CD3 monoclonal antibody. In summary, short-term respiratory exposure of mice to DEP resulted in systemic immunosuppression with evidence of T cell-mediated and possibly macrophage-mediated mechanisms.     

Triggers of hair cell regeneration in the avian inner ear

We performed an in vitro study in order to determine possible triggers of hair cell regeneration in the chick basilar papilla following degeneration. We compared the response of sensory epithelium damaged by collagenase treatment with that damaged by acoustic trauma. The former exhibited no proliferative activity, but the latter did. The basilar papillae damaged by acoustic trauma could have proliferating activity in medium containing fetal bovine serum (FBS) or epidermal growth factor (EGF) but not in the medium without FBS or EGF. These findings indicate that regeneration of basilar papillae depends on the manner of cell death and that FBS or EGF is required for regeneration.     

妊娠期接受MRI磁场照射对子代大鼠不同发育期MAPK的影响

【目的】　研究妊娠期接受磁共振 (magneticresonanceimaging ,MRI)复合磁场照射对子代大鼠不同发育期脑部丝裂原活化蛋白激酶 (mitogenactivatedproteinkinase ,MAPK) /细胞外信号调节蛋白激酶 (extracellularsignalregulatedproteinkinase ,ERK )表达的影响。 　【方法】　SD孕鼠妊娠第 12～ 18d给予 0 .3 5TMRI磁场照射 ,雌性子鼠1、2、5月龄时进行大脑切片免疫组化SP方法染色 ,并用图像分析仪进行半定量分析。　【结果】　MAPK/ERK免疫反应在大鼠脑切片上广泛表达 ;随着年龄增长 ,未发现其表达的变化 ;在各年龄段子鼠照射组和对照组间MAPK/ERK的免疫反应表达差异均无显著性 (P >0 .0 5 )。　【结论】　妊娠期MRI磁场照射后并未引起子代大鼠MAPK/ERK免疫反应表达的异常     

In vivo percutaneous absorption of arsenic from water and CCA-treated wood residue.

This study was conducted to evaluate the dermal absorption of arsenic from residues present on the surface of wood preserved with chromated copper arsenate (CCA). The research reported herein used methods parallel to those of earlier research on the dermal absorption of radiolabeled arsenic (R. C. Wester et al., 1993, Fund. Appl. Toxicol. 20, 336-340), with modifications to allow use of environmental matrices that are not radiolabeled. These modifications include the surface area of application and dietary intake of arsenic, thus maximizing the potential for detection of dermally absorbed arsenic in exposed animals above diet-associated background levels of exposure. Two forms of arsenic were administered in this work. The first, arsenic in solution, was applied to the skin of monkeys to calibrate the model against prior absorption research and to serve as the basis of comparison for absorption of arsenic from CCA-treated wood residues. The second substrate was residue that resides on the surface of CCA-treated wood. Results from this research indicate that this study methodology can be used to evaluate dermally absorbed arsenic without the use of a radiolabel. Urinary excretion of arsenic above background levels can be measured following application of soluble arsenic, and absorption rates (0.6-4.4% absorption) are consistent with prior research using the more sensitive, radiolabeled technique. Additionally, the results show that arsenic is poorly absorbed from CCA-treated wood residues (i.e., does not result in urinary arsenic excretion above background levels).     

叙事暴露疗法在儿童和青少年创伤后应激障碍患者中应用效果的Meta分析

背景 叙事暴露疗法（NET）结合叙事疗法和暴露疗法的优点,对缓解创伤后应激障碍（PTSD）症状有效,有助于患者对创伤进行深入的认识,也具有较好的安全性。儿童和青少年是PTSD的高发人群,但NET对该人群干预效果的研究结果存在差异。目的 系统评价NET对儿童和青少年PTSD患者的干预效果,为NET的临床应用提供参考。方法 于2022年8月1日,计算机检索Cochrane Library、PubMed、Web of Science、CINAHL、中国知网（CNKI）、中国生物医学文献数据库（SinoMed）、维普数据库和万方数据库,检索时限为建库至2022年6月。采用主题词与自由词相结合的方式进行检索,收集NET治疗儿童和青少年PTSD的文献。根据Cochrane协作网更新的偏倚风险评估手册中对随机对照试验的真实性评价标准（2011）,评价文献质量。采用RevMan 5.4对纳入的随机对照试验进行Meta分析。结果 纳入9篇文献,共包括394例儿童和青少年PTSD患者。Meta分析结果显示,在PTSD症状缓解程度方面,干预后1~3个月（SMD=0.22,95% CI：-0.84~1.28）以及干预后6个月（SMD=0.21,95% CI：-0.75~1.17）,NET与放松疗法的效果比较,差异无统计学意义;干预后1~3个月（SMD=-0.66,95% CI：-1.04~-0.27）以及干预后6个月（SMD=-0.77,95% CI：-1.36~-0.19）,NET的效果均优于常规治疗,差异均有统计学意义。在抑郁症状缓解程度方面,治疗后1~3个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.39,95% CI：-0.98~0.21）;干预后6个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.74,95% CI：-2.23~0.75）。在心理困扰缓解程度方面,干预后1~3个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.54,95% CI：-2.14~1.07）。在食欲亢进缓解程度方面,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.17,95% CI：-0.54~0.19）。结论 与常规治疗相比,NET对缓解儿童和青少年PTSD症状的效果更佳,且具有中长期效果,但在改善抑郁症状、心理困扰以及食欲亢进方面无明显优势。     

Deterministic and Probabilistic Dietary Exposure Assessment to Deoxynivalenol in Spain and the Catalonia Region

Deoxynivalenol (DON) remains one of the most concerning mycotoxins produced by the Fusarium genus due to the wide occurrence in highly consumed cereal-based food and its associated toxicological effects. Previous studies conducted in Spain and other European countries suggested that some vulnerable groups such as children could be exceeding the tolerable daily intakes. Thus, the aim of this study was to conduct a comprehensive and updated dietary exposure assessment study in Spain, with a specific analysis in the region of Catalonia. Cereal-based food samples collected during 2019 were analysed using liquid chromatography coupled to tandem mass spectrometry for multi-mycotoxin detection including DON and its main metabolites and derivatives. Consumption data were gathered from the nation-wide food surveys ENALIA and ENALIA2 conducted in Spain, and a specific survey conducted in Catalonia. The data were combined using deterministic and semi-parametric probabilistic methods. The results showed that DON was widely present in cereal-based food highly consumed in Spain and the Catalonia region. Exposure to DON among the adult population was globally low; however, among infants aged 3–9 years, it resulted in the median of 192 ng/kg body weight/day and the 95th percentiles of 604 ng/kg body weight/day, that would exceed the most conservative safety threshold for infants. Bread and pasta were the main contributing foodstuffs to the global exposure to DON, even among infants; thus, those foods should be considered a priority for food control or to develop strategies to reduce the exposure. In any case, further toxicological and epidemiological studies are required in order to refine the safety thresholds accounting for the sensitivity of the infant population.     

The effect of tightened hearing protection regulations on military noise-induced tinnitus

The objective of this study was to investigate the effect of tightened hearing protection regulations on tinnitus in the Finnish Defence Forces. The initial study group comprised 252 officers and non-commissioned officers (NCOs), of which 229 were included in the final study group. Subjective symptoms of tinnitus and audiometric test results for these officers and NCOs examined before retirement, from 1984 to 1986 (Period I), and 2003 to 2005 (Period II), were reviewed. Changes in tinnitus reports between the two time periods, during which regulations had been revised, were investigated. Prevalence of tinnitus showed a decline both in officers (from 68% to 63%) and in NCOs (from 76% to 72%) between the two study periods, in accordance with tightened hearing protection regulations. The Cox regression analysis showed a significantly decreased hazard ratio for constant or disturbing tinnitus for Period II. Tinnitus prevalence, especially constant or disturbing tinnitus, in the Finnish Defence Forces was diminished by tightened hearing protection regulations. Tinnitus might be more persistent than hearing loss and does not necessarily improve in direct relation to hearing loss after protective measures.