Developmental neurotoxicology

The developing brain has a distinctive set of characteristics that make it unusually sensitive to damage by toxic agents. Mechanistic understanding of the vulnerability of the immature nervous system to various chemicals is important from a preventive perspective but has also frequently given us new insights into maturation of neural circuitry. This review examines some of the developmental consequences of contact with various exogenous agents, including metals, solvents, pharmaceuticals, and natural products. This review emphasizes how subtle suboptimal brain function rather than acute toxicity can be a consequence of chemical exposures occurring during ontogenesis. The rate of brain aging may be influenced by events taking place in embryogenesis, following a prolonged asymptomatic period. The potential for appearance of adverse effects after prolonged latent periods is underscored.     

Involvement of the extracellular signal regulated kinase pathway in hydrocarbon-induced reactive oxygen species formation in human neutrophil granulocytes

In the present study we have examined the effects of hydrocarbons on the formation of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We found that hydrocarbons induce ROS formation in a concentration-dependent manner and that the ROS-inducing potency increases with increasing number of carbon atoms in the structure. In general, aromatic hydrocarbons were less potent inducers of ROS than aliphatic and cyclic hydrocarbons. The most potent compound in each group, t-butylcyclohexane, n-decane, and n-butylbenzene, were chosen for mechanistic studies. ROS formation was inhibited by the MEK1/2 inhibitor U0126, the tyrosine kinase inhibitor erbstatin-A, and the phosphatidylinositol-3 kinase inhibitor wortmannin. The involvement of the ERK1/2 pathway was confirmed by Western blot analysis of phosphorylated ERK1/2. The study revealed only small differences in the mechanisms involved for the three compounds. The responses were not affected by Pertussis toxin, indicating that Gi-protein coupled receptors are not involved in neutrophil activation after hydrocarbon exposure. Based on these findings we propose a mechanism involving tyrosine kinases, PI3 kinase, and the ERK1/2 pathway, leading to activation of the NADPH oxidase and production of ROS in neutrophils stimulated by organic solvents.     

Routine diagnostic procedures for chronic encephalopathy induced by solvents: survey of experts

OBJECTIVES—To study the routine diagnostic procedures used in different countries for chronic toxic encephalopathy (CTE) induced by solvents.
METHODS—By means of a postal questionnaire selected international experts were asked about the methods they use to diagnose patients suspected of having CTE induced by solvents, the number of patients, entrance criteria, and the results of these diagnostic procedures.
RESULTS—18 Experts working in 18 diagnostic centres responded. Most of them agreed that a diagnostic procedure for CTE induced by solvents should contain an interview and neurological, physical, and neuropsychological examinations. However, the tests used were very different, as were the classifications for CTE. Depending on the institute, a diagnosis of CTE was made in 6%-70% of the referred patients. The proportion of patients with CTE stage I ranged from 0% to 33%, stage II from 5% to 100%, and stage III from 0% to 95%.
CONCLUSION—The intentions of the two 1985 conferences that aimed at clarity and uniformity of diagnosis of CTE induced by solvents are far from reached. It is possible, now the conditions are more favourable, to aim at this important goal and recommend some refinement of the then proposed criteria.


     

顶空毛细管气相色谱法测定医疗器械中环氧乙烷的残留量

目的建立医疗器械中环氧乙烷残留量的顶空一毛细管气相色谱测定法。方法HP-5色谱柱（30m×250gm×0．25gm）．氢火焰离子化检测器（FID），柱温为120℃，保持8分钟：进样13温度为200℃．检测器温度为250℃。结果：环氧乙烷在5．1920—51．920μg范围内呈线性关系（r=0．997，n=6），检测限为1μg；注射器中的环氧乙烷的平均回收率为103．3％，输液器中环氧乙烷的平均回收率为81．04％。结论：经方法学验证，该方法灵敏度、准确度均达到有机溶剂残留量测定的要求，可用于输液器、注射器中环氧乙烷残留量的测定。     

气相色谱法测定富马酸比索洛尔中有机残留量

目的:建立富马酸比索洛尔原料药中乙醇及乙酸乙酯残留量的测定方法:方法:采用气相色谱法测定,色谱柱为AT·PEG-20 M毛细管柱(30 m×0.53 mm×1.0 μm),以N2为载气,FID检测器,进样口温度:200 ℃,检测器温度:250 ℃,柱温为程序升温:初始温度40 ℃保持3 min,以每分钟8 ℃的速度升至180 ℃,N2流量为7 mL/min,分流比为20∶1.结果:待测物均得到较好的分离,且线性关系良好.结论:本方法简便,可用于富马酸比索洛尔原料药中有机溶剂残留量的测定.     

Chemical Uptake Into Human Stratum Corneum In Vivo from Volatile and Non-Volatile Solvents

Purpose. Simple, safe and quick in vivo methods for estimating chemical uptake into the stratum corneum (SC) from volatile and non-volatile solvents are invaluable to health risk assessors. This study compares the human in vivo SC uptake of a model compound (4-cyanophenol) from water and acetone using quantitative attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Methods. Small areas on the ventral forearms of human volunteers were treated with 4-cyanophenol (CP) dissolved either in water or acetone. After the skin was cleansed of remaining surface CP, SC samples were taken by a standard tape-stripping method. CP concentration profiles across the SC were quantitated by direct measurement of the permeant on the individual tape-strips using ATR-FTIR. Results. Increasing the duration of exposure to CP aqueous solutions resulted in increasing CP uptake into the SC; the kinetics of uptake correlated well with predictive diffusion equations. Increasing the 'dose' of CP in acetone also resulted in increasing uptake into the SC, but uptake eventually plateaued at a maximum level. The amount of CP taken up into the SC from acetone was 2 to 8-fold greater than that from water following similar short-time exposures. Conclusions. These safe, simple experimental methods provide practical and predictive assessments of chemical uptake into human SC in vivo.     

Occupational exposure to solvents and cerebellar,brainstem and vestibular functions

Summary Forty-eight persons (age 44, SD 9 years) exposed to paint solvents and 40 nonexposed referents (age 45, SD 9 years) were examined. The duration of exposure was 4 to 30 (mean 20) years and the life-time exposure level was estimated to have been 10 to 330 (mean 60%) of the hygienic standard. The methods used were a neurological examination, electroencephalography, brainstem auditory-evoked potentials, electronystagmography, and posturography. Lifetime exposure was estimated on the basis of a detailed occupational history and environmental measurements made at the work places over several years. The average weekly alcohol consumption was established in a detailed interview. Due to the small number of subjects examined, the study was inconclusive. The findings classified as abnormal were slightly more common in the exposed than in the referents, and in the persons who used alcohol than in the non-users. The differences were not statistically significant, and no exposure-response relationships were found.     

An examination of factors that could affect choice reaction time in histology technicians

Histology technicians exposed to formaldehyde and solvents have symptoms and objective evidence of neurobehavioral impairment of memory, judgment, and equilibrium. Because reaction time has been prolonged in many groups of workers exposed to toxicants, choice reaction time was measured in 385 female formaldehyde and solvent-exposed histology technicians, and 79 unexposed female laboratory workers. Choice reaction time to a visual stimulus (CRT) is defined, for the purpose of this study, as the time required for discriminated cancellation of two different letters on a microcomputer screen by pressing the matching keys. Initial analysis showed that increases in age, years of cigarette smoking, and hours per day of formaldehyde exposure significantly lengthened CRT, but xylene-toluene exposure had no effect. Since duration of smoking and length of daily formaldehyde exposure were age related, multiple linear regression analysis of CRT was performed using them as independent variables. Increasing age was the only significant factor in lengthening CRT. However, in these female histology technicians, the second measurement one year later was 44 msec faster (p less than .04). The reason for improved performance is unclear, but it may be an effect of training encompassing familiarity, improved attention, or learning.