Biological monitoring of occupational exposure to isopropyl alcohol vapor by urinalysis for acetone

Summary The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time-weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non-exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm.A part of this work was presented at 62nd Annual Meeting of Japan Association of Industrial Health, held in Hirosaki, Japan, on 27th–30th, April, 1989     

Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats

Pulmonary changes in glutathione (GSH) indicated by the concentration of non-protein sulphydryls showed a decrease of 43% in rats exposed for 5 h per day three times to 500 cm³/m³ (2100 mg/m³) styrene vapour. In these rats, only a marginal decrease was observed in the pulmonary cytochrome P450 oxidative metabolism. Following a single 24-h inhalation exposure to 500 cm³/m³ styrene, the decreases in GSH were 66% in lung but only 16% in liver. On the other hand, a multifold increase in the disposition of thioether compounds was found in urine. Pulmonary cytochrome P450-dependent metabolism was decreased, shown by low residual activities of 7-ethoxyresorufin (<20%), 7-ethoxycoumarin (53%) and 7-pentoxyresorufin O-dealkylases (76%). Epoxide hydrolase and GSH S-transferase enzyme activities which catalyze styrene detoxification were not decreased. Styrene exposure (24 h) of acetone-, phénobarbitalor 3-methylcholanthrene-pretreated rats resulted in pulmonary effects different from each other and from those of styrene alone. Acetone potentiated the lung effect and elevated 1.5-fold urine thioether output. Inducer pretreatment seemed to be a factor aggravating styrene toxicity; in effect this was clearest in acetone-induced rats. In general, GSH depletion accompanied by inhibition of cytochrome P450-dependent oxidative drug metabolism were the earliest biochemical lesions manifested in styrene-exposed lung.     

牙本质表面状态对丙酮基粘结剂强度和界面的影响

目的：研究干燥或湿润的牙本质表面状态对丙酮基粘结剂粘结强度和粘结界面微观结构的影响，并探讨粘结强度和粘结界面微观结构之间的内在联系。方法：选用3种含有丙酮的湿粘结系统Gluma One-Bond、Bond-1和One-Step，将Chrisma树脂分别粘结在干燥或湿润的人牙本质表面，测试各组试件的微拉伸强度，并用扫描电镜观察和比较各组试件粘结界面超微结构的异同。结果：湿粘结时，粘结剂对牙本质表面的渗透较为充分，混合层均匀，厚度约为5μm，并可观察到牙本质小管和侧支小管中有明显的树脂突形成；干燥粘结时，形成的混合层变薄，并有不完全渗透的混杂层形成。干燥粘结时，3种粘结系统的微拉伸强度均有显著降低，下降幅度最高为39％，微拉伸破坏的方式主要是粘结界面的破坏。结论：含有丙酮的粘结系统在干燥粘结时，对牙本质表面的渗透性下降，微拉伸强度明显降低；微拉伸强度的测试，可以更客观地反映粘结强度的大小。     

气相色谱测定盐酸头孢吡肟中残留甲醇、乙醇和丙酮的含量

目的建立用气相色谱(GC)测定盐酸头孢吡肟中残留溶剂甲醇、乙醇和丙酮的方法。方法采用GDX-101色谱柱(3mm×2 m),N2为载气,氢焰离子化检测器,N,N-二甲基甲酰胺-水(8∶2)为溶剂,直接进样,外标法计算残留溶剂的含量。结果甲醇、乙醇和丙酮均完全分离;甲醇在15~300μg.ml-1,乙醇和丙酮在25~500μg.ml-1的范围内线性关系良好,r分别为0.99810、.9997、0.9990;平均加样回收率甲醇为98.51%(RSD=1.29%,n=5),乙醇为100.9%(RSD=2.37%,n=5),丙酮为97.09%(RSD=3.31%,n=5);检测限分别为3.0、1.0、20.0μg.ml-1。结论方便简便、重复性好,结果准确。     

固相微萃取-气相色谱法测定阿奇霉素中丙酮残留量

目的：建立以顶空-固相微萃取-气相色谱联用技术测定阿奇霉素中丙酮残留量的方法。方法：使用自制新型萃取头（苯-丙-硅共聚物）,气-液平衡时间：25min,萃取时间：20min。色谱柱为不锈钢柱（内填充二乙烯苯-乙基乙烯苯型高分子小球,2m×3mm）。结果：丙酮测定结果的RSD为0.64%,在0.10～16.00μg/g范围内呈良好的线性关系（r=0.9947）,回收率为98.7%～104%。结论：本方法快速、准确、重现性好,可用于阿奇霉素中丙酮残留量的测定。     

Synergistic effects of chlorpyrifos with piperonyl butoxide (pbo) against the lesser mealworm,Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae)

ObjectiveTo investigate the co-toxicity and co-efficient activity of Chlorpyrifos (Dursban 20EC), an organophosphate and Piperonyl butoxide (PBO) against the lesser meal worm Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) (A. diaperinus).MethodsThe repellent activity was carried out by the residual film assay technique. Statistically the dose mortality relationship was expressed as a median lethal dose (LD₅₀) by the probit analysis. The regression lines and isoboles were drawn using the Fig-P (Biosoft) package.ResultsThe Co-efficient values showed that all ratios of chlorpyrifos and piperonyl butoxide offered synergistic action to both larvae and adult. We observed that the toxicity of the chlorpyrifos was decreased as the ratio (amount) of PBO was increased. The individual LD₅₀ value of chlorpyrifos for adult is 0.1241 µg/cm². But in the mixture, the share of chlorpyrifos are 0.0298, 0.0366, 0.0246 and 0.0108 µg/cm² at ratios of 1:1, 1:3, 1:5, 1:10 when PBO causes reduction of dose level of 75.84%, 70.53 %, 80.19% and 91.30% respectively. In case of larvae the individual LD₅₀ value of chlorpyrifos is 0.2943 µg/cm². But in the mixture, the share of chlorpyrifos are 0.05, 0.019, 0.015 and 0.010 µg/cm at ratios of 1:1, 1:3, 1:5;1:10 when PBO causes reduction of dose level of 80.01%, 93.54%, 94.90% and 96.60% respectively.ConclusionsThe study suggests that the mortality rate of lesser meal worm is increase with the increase of insecticide dose. The LD₅₀ values of the insecticides are inversely related to the toxicity of the insecticides i.e. higher the LD₅₀ value lower the toxicity of the insecticide.     

某企业偶氮二异丁腈车间主要职业病危害因素识别与关键控制点分析

目的识别某企业偶氮二异丁腈车间的职业病危害因素,检测其危害程度,找出职业病危害的关键控制点。方法采用职业卫生现场调查、职业卫生检测和综合分析法进行评价。结果该项目存在的职业病危害因素有粉尘、化学毒物和噪声,粉尘、化学毒物和噪声分别检测6、8和4个岗位。粉尘浓度为0.3~2.7 mg/m3,合格率100%;存在的化学毒物为甲醇、硫酸、丙酮氰醇和过氧化氢,浓度分别为40.9~796.0 mg/m3、0.3 mg/m3、0.1~1.0mg/m3和0.9~1.1 mg/m3。除甲醇合格率为50%外,其余均低于职业接触限值;噪声强度为80.5~89.6 dB(A),超标率为50%。结论甲醇、丙酮氰醇和噪声是偶氮二异丁腈生产过程中职业病危害因素重点分析因素。     

Tissue distribution, effects of cooking and parameters affecting the extraction of azaspiracids from mussels, Mytilus edulis, prior to analysis by liquid chromatography coupled to mass spectrometry.

This study used liquid chromatography coupled to mass spectrometry to identify some parameters important in the analysis of azaspiracids. The first aspect was the distribution of azaspiracids within mussels, in particular the content in the digestive gland as compared to the remaining tissues. In our study, azaspiracids accumulated in the digestive gland, similar to other lipophilic toxins. The ratio of toxin in the digestive gland compared to the whole mussel was on average circa 5, both for a bulk sample collected in Norway in 2004 and for 28 samples from Ireland collected over 3 years (2001-2003). These results may justify the practise to only analyse the digestive gland, a step considered necessary to achieve adequate detection limits for azaspiracids both in the mouse bioassay and other analytical techniques. Steaming of mussels as a sample pre-treatment was found to be another parameter affecting the result. Azaspiracids concentrated indirectly, i.e. through the loss of water or juice from the matrix. The cooked shellfish tissues had a concentration of azaspiracids 2-fold higher than the uncooked shellfish, both for whole flesh and for digestive gland tissue. This finding is of particular importance since it may affect the maximum guidance level at which shellfish may be allowed for human consumption. Finally, parameters affecting the extraction efficiency were studied, including the nature of the extraction solvent, the sample-to-solvent ratio and replicate extraction. The largest differences were observed between different solvents and between different sample-to-solvent ratios, while the effect of replicate extraction was minimal if large sample-to-solvent ratios were used. Duplicate extraction using 100% methanol was found to be the best combination of parameters.     

The Identification and Quantitation of Malondialdehyde,Formaldehyde, Acetaldehyde,and Acetone in Serum of Rats

A high-pressure liquid chromatographic (HPLC) method has been developed for the simultaneous determination of serum levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone. Serum samples were derivatized with 2,4-dinitrophenylhydrazine (DNPH) to form the corresponding hydrazones of the four lipid metabolites. The hydrazones were extracted with pentane and chromato-graphed on a μ Bondapak C₁₈ column. Acetonitrile-water (49:51 v/v) was used as the mobile phase. Treatment of rats with 2, 4, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (50 μg/kg) resulted in marked time-dependent increases in the serum levels of the four metabolites. This HPLC method for identifying and quantitating formaldehyde, malondialdehyde, acetaldehyde, and acetone is rapid and highly reproducible. The method has widespread applicability to the assessment of metabolic alterations produced by drugs, disease states, and toxicants.     

Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice

Purpose:   Acetone is the principal ketone body elevated in the ketogenic diet (KD), with demonstrated robust anticonvulsant properties across a variety of seizure tests and models of epilepsy. Because the majority of patients continue to receive antiepileptic drugs (AEDs) during KD treatment, interactions between acetone and AEDs may have important clinical implications. Therefore, we investigated whether acetone could affect the anticonvulsant activity and pharmacokinetic properties of several AEDs against maximal electroshock (MES)–induced seizures in mice.
Methods:   Effects of acetone given in subthreshold doses were tested on the anticonvulsant effects of carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM) and valproate (VPA) against MES-induced seizures in mice. In addition, acute adverse effects of acetone–AEDs combinations were assessed in the chimney test (motor performance) and passive avoidance task (long-term memory). Pharmacokinetic interactions between acetone and AEDs were also studied in the mouse brain tissue.
Results:   Acetone (5 or 7.5 mmol/kg, intraperitoneally [i.p.]) enhanced the anticonvulsant activity of CBZ, LTG, PB, and VPA against MES-induced seizures; effects of OXC, PHT, and TPM were not changed. Acetone (7.5 mmol/kg) did not enhance the acute adverse-effect profiles of the studied AEDs. Acetone (5 or 7.5 mmol/kg, i.p.) did not affect total brain concentrations of the studied AEDs. In contrast, VPA, CBZ, LTG, OXC, and TPM significantly decreased the concentration of free acetone in the brain; PB and PHT had no effect.
Conclusions:   Acetone enhances the anticonvulsant effects of several AEDs such as VPA, CBZ, LTG, and PB without affecting their pharmacokinetic and side-effect profiles.