Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied

An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential. The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally. Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 μg/cm² for chemicals assessed as reactive. This would protect against 95% of chemicals assessed as reactive, but the remaining 5% would include chemicals with very high potency. Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST.     

Extension of the Dermal Sensitisation Threshold (DST) approach to incorporate chemicals classified as reactive

The evaluation of chemicals for their skin sensitising potential is an essential step in ensuring the safety of ingredients in consumer products. Similar to the Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has been demonstrated to provide effective risk assessments for skin sensitisation in cases where human exposure is low. The DST was originally developed based on a Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not considered to be directly reactive to skin proteins, and unlikely to initiate the first mechanistic steps leading to the induction of sensitisation. Here we have extended the DST concept to protein reactive chemicals. A probabilistic assessment of the original DST dataset was conducted and a threshold of 64 μg/cm² was derived. In our accompanying publication, a set of structural chemistry based rules was developed to proactively identify highly reactive and potentially highly potent materials which should be excluded from the DST approach. The DST and rule set were benchmarked against a test set of chemicals with LLNA/human data. It is concluded that by combining the reactive DST with knowledge of chemistry a threshold can be established below which there is no appreciable risk of sensitisation for protein-reactive chemicals.     

突发性聋患者耳蜗死区分布及预后分析

目的：采用阈值均衡噪声检测法研究耳蜗死区在突发性聋患者中的分布情况,探讨耳蜗死区与突发性聋预后的关系。方法采用阈值均衡噪声检测法检测138例（149耳）突发性聋患者,综合治疗2周后,再次行听力检测,分析耳蜗死区和突发性聋预后的相关性。结果138例（149耳）突发性聋患者中39例患者（45耳）单或双耳存在一个或多个频率的耳蜗死区,耳蜗死区检出率为30.20%（45/149）;耳蜗死区在突发性聋患者主要分布在2000～4000 Hz的高频区域;检测有听力下降的频率993个,其中有耳蜗死区的频率103个,治疗后有效率29.13％（30/103）;经检测无耳蜗死区的频率890个,治疗后有效率54.38％（484/890）。两组有效率进行比较,差异具有统计学意义（χ2=23.58,P<0.05）。结论耳蜗死区与突发性聋预后密切相关。     

Lateralisation in wine olfactory threshold detection: Comparison between experts and novices

The study of olfactory lateralisation in humans has given rise to many publications, but few studies have been focused on possible differences in relation to the experience towards specific odorants. The aim of the present study was to compare unilateral detection thresholds for three wines between expert and novice judges. Additionally, irritation and hedonic valence were also evaluated using monorhinal stimulations. Results showed that the novices had lower detection thresholds with the left nostril—whatever the wine—compared to the experts. Concerning hedonic rating, no nostril difference existed in the expert group contrary to the novice group, which evaluated wines as more pleasant with the left than with the right nostril. Irritation rating appeared not to be lateralised in both groups. However, the novices rated the three wines as more irritant than the experts with the right as well as with the left nostril. These findings suggest that the level of experience induced specific differences in terms of lateralisation between wine experts and novices.     

Non-flat audiograms in sensorineural hearing loss and speech perception

OBJECTIVE:

The audibility thresholds for the sound frequency of 137 upward- and downward-sloping audiograms showing sensorineural hearing loss were selected and analyzed in conjunction with speech recognition thresholds obtained from individuals seen at a public otolaryngology clinic to determine which frequencies in slope audiograms best represent speech recognition thresholds.

METHOD:

The linear regression model and mean square error were used to determine the associations between the threshold values.

RESULT:

The mean square error identified larger errors when using thresholds of 500, 1000, and 2000 Hz than when using audibility thresholds of 500, 1000, 2000, and 4000 Hz. The linear regression model showed a higher correlation (91%) between the audiogram thresholds for frequencies of 500, 1000, 2000, and 4000 Hz than for the frequencies of 500, 1000, and 2000 Hz (88%).

CONCLUSION:

Frequencies of 500, 1000, 2000, and 4000 Hz were the most significant in predicting the speech recognition threshold.     

Threshold of Tactile Perception After Nipple-Sharing: a Prospective Study

Reconstruction of the nipple-areola complex is the final procedure of a breast reconstruction. The method of choice in our department for nipple reconstruction is nipple-sharing and tattooing of the areola. Some patients are reluctant to use a part of the healthy nipple, as it is not fully known how the sensibility in the remaining donor nipple is affected by surgery. Twenty patients admitted to the hospital for nipple-sharing were invited to participate in the study. The tactile perception threshold of the donor nipple was assessed using von Frey monofilaments preoperatively, and 1, 6, and 12 months postoperatively. The patients' subjective impressions one year postoperatively were also evaluated. The donor nipple had regained sensibility to touch six months after nipple-sharing. All patients reported that the nipple felt the same as before surgery and could become erect. We therefore recommend the nipple-sharing technique for completion of a breast reconstruction.     

Doppler ultrasound wall removal based on the spatial correlation of wavelet coefficients

In medical Doppler ultrasound systems, a high-pass filter is commonly used to reject echoes from the vessel wall. However, this leads to the loss of the information from the low velocity blood flow. Here a spatially selective noise filtration algorithm cooperating with a threshold denoising based on wavelets coefficients is applied to estimate the wall clutter. Then the blood flow signal is extracted by subtracting the wall clutter from the mixed signal. Experiments on computer simulated signals with various clutter-to-blood power ratios indicate that this method achieves a lower mean relative error of spectrum than the high-pass filtering and other two previously published separation methods based on the recursive principle component analysis and the irregular sampling and iterative reconstruction, respectively. The method also performs well when applied to in vivo carotid signals. All results suggest that this approach can be implemented as a clutter rejection filter in Doppler ultrasound instruments.     

压水堆核电站燃料元件包壳破损监测通道报警阈值研究

目的 建立压水堆核电站不同运行工况下燃料元件包壳破损监测通道测量值的计算方法,计算在三种一回路冷却剂浓度条件下监测通道的剂量率,指导该监测通道报警阈值的设置。方法 分析了压水堆核电站各种工况情况下一回路冷却剂中的放射性核素,根据燃料元件包壳破损监测通道的实际设计情况,采用MCAM建模软件建立了可用于MCNP软件计算的模型,计算了三种不同工况情况下元件包壳破损监测通道的测量值。结果 三种工况条件下,该监测通道的计算值分别为8.0×10^-6、5.3×10^-4、1.6×10^-3Gy/h。结论 建议将5.3×10^-4、1.6×10^-3Gy/h分别设置为一级和二级报警阈值,该两级报警阈值的设置均与现役电站运行阈值相当。