吡嘧黄隆生产中的过敏反应解析

本文对吡嘧黄隆生产中的原料和中间体氰乙酸民酯，乙氧基甲叉氰乙酸乙酯和吡唑胺进行了致繁性试验研究。结果表明，乙氧基甲叉氰乙酸乙酯是致敏原。为解决吡嘧黄隆生产中操作人员的过敏性皮炎提供了依据。     

Effects of Indoor Air Pollution on Human Health

This article contains a summary discussion of human health effects linked to indoor air pollution (UP) in homes and other non-industrial environments. Rather than discussing the health effects of the many different pollutants which can be found in indoor air, the approach has been to group broad categories of adverse health effects in separate chapters, and describe the relevant indoor exposures which may give rise to these health effects. The following groups of effects have been comdered: effects on the respiratory system; allergy and other effects on the immune system; cancer and effects on reproduction: effects on the skin and mucous membranes in the eyes, nose and throat; sensory effects and other effects on the nervous system; effects on the cardiovascular system; systemic effects on the liver, kidney and gastro-intestinal system. For each of these groups, effects associated with IAP the principal agents and sources, evidence linking IAP to the effects, susceptible groups, the public health relevance, methods for assessment, and major research needs are briefly discussed. For some groups of effects, clear relationships with exposure to IAP have been reported in the world literature. Among these are respiratory disease (particularly among children), allergy (particularly to house dust mites) and mucous membrane irritation (particularly due to formaldehyde). Large numbers of people have been, and are still being affected. Many chemicals encountered in indoor air are known or suspected to cause sensory irritation or stimulation. These, in turn, may give rise to a sense of discomfort and other symptums cummonly reported in so-called “sick” buildings. Camplex mixtures of organic chemicals in indoor air also have the potential to invoke subtle effects on the central and peripheral nervous system, leading to changes in behaviour and performance. An increased risk of developing lung cancer has been linked to exposure to environmental tobacco smoke (ETS) and to radon decay products. Lung cancer is a very serious disease with a high fatality rate; however, the number of people affected is much lower than the number of people contracting resparatory disease or alhgies, or experiencing irritative effects due to exposure to indoor pollution. The effects of IAP on reproduction, cardiovascular disease and on other systems and organs have not been well documented to date. To a certain extent, this may mean that no serious effects occur, but there has been little by way of research to clearly document the absence of these tvpes of effects.     

The eye irritation and odor potencies of four terpenes which are major constituents of the emissions of VOCs from Nordic soft woods

Eye goggles were used to estimate human thresholds for sensory eye irritation from four monoterpenes: (+)3-carene, (-)limonene and (+)alpha-pinene and (rac)alpha-terpineol all known as air pollutants emitted from wood. Only a ranking of the irritation thresholds relative to that of n-butanol is given. The measurements showed that the thresholds for eye irritation of the terpenes ranged from subthreshold to below 1,250 mg/m3. It appears that the irritation of 3-carene and limonene in contrast to the expectations was of the same size as or less than that of n-butanol. Too few subjects reported eye-irritation for alpha-pinene and alpha-terpineol to allow estimates of thresholds of these compounds which therefore have much less irritative potency than n-butanol, 3-carene, and limonene. The measurements of one terpene alcohol do not support the hypothesis that monoterpene alcohols, would have lower eye irritation threshold than monoterpene hydrocarbons. The sequence from strongest odorant to weakest was alpha-terpineol, 3-carene, n-butanol, limonene and alpha-pinene. In conclusion, the tested terpenes can probably be ruled out as cause of acute eye irritation indoors. The measured odor thresholds did not deviate from the few values reported in the literature.     

Anti-irritant potential of cosmetic raw materials and formulations

The investigation studied the anti-irritant potential of several substances commonly employed in cosmetic formulations as basic components of the emulsion or as active ingredients, and evaluated the effect of the emulsifier. Five different emulsions were made irritating by addition of croton oil, in sufficient quantity to provoke a clearly adverse reaction in the rabbit, i.e. primary cutaneous irritation index (PII) close to 2. The PII was determined according to the official French methods by applying to symmetrical areas of the back, the irritant base as control and the same base containing the test substance. Fifty-five ingredients were evaluated: gelling agents, plant extracts, molecules defined as healing, anti-inflammatory substances or anaesthesic compounds, etc. The test substances were added to the emulsion at concentrations close to the ones generally found in cosmetics. The qualitative and the quantitative composition of the oil phase was similar for each emulsion.
Several gelling agents, thickeners and polymers which notably reduce skin contact with an irritant, gave good results. Some of the usual healing, anti-inflammatory, local anaesthesic compounds gave the expected results. Some ingredients, though well known, were ineffective. The type of emulsifier, by modifying cutaneous penetration and bio-availability of the active ingredients, may play an important role.
Le potential anti-irritant de constituants de base et compositions cosmétiques     

Low relative humidity and aircraft cabin air quality

Mucosal irritation remains a common complaint among travelers and flight attendants in aircraft cabins. Despite the fact that very low humidity is routinely encountered, few studies of its effects have been conducted in the cabin environment. The authors reviewed chamber and field studies in the experimental literature to explore whether there is an association and, if so, at what level it was likely to be present. Subjects who participated in prior research were not always able to perceive low humidity or changes in the humidity level and, at times, this inability has been confused in the literature with the lack of a humidity effect. The studies with more powerful experimental designs have demonstrated the effects of low humidity, such as drying of the skin and mucus membranes, and that a modest increase in relative humidity seems to alleviate a great number of symptoms. The exposure duration below during which the effects of low humidity are not noticeable is in the order of 3 to 4 h. It is conceivable that some symptoms experienced by flight attendants and passengers, especially on flights lasting 3 h or longer, may stem from low humidity.     

Increasing quality of life by improving the quality of skin in patients with atopic dermatitis

Atopic dermatitis is a chronic relapsing inflammatory skin disease which usually starts during the first years of life. In patients with the disease, the quality of skin is severely affected, and this is closely linked to a reduced quality of life. An increasing prevalence of the disease has also been observed during recent years, which has been attributed to potential provocation factors in the environment. The environmental influence of the disease is complex, but the role of stratum corneum as a biosensor regulating the response to a variety of insults has been suggested as one crucial factor. Therefore, our daily hygiene and treatment of dryness are necessary measures to improve the quality of life and possibly reduce the frequency of the disease. Soaps as well as moisturizers show important differences in their impact on barrier function.     

The modern office environment desiccates the eyes?

Eye irritation is a common complaint in the office environment. The purpose of this overview is to merge knowledge within indoor air science, ophthalmology, and occupational health to promote understanding eye irritation symptomatology, the cause of which is still partly unknown. High periocular relative humidity appears to protect the pre-corneal tear film against desiccation and sensory irritating pollutants and reduces the development of eye irritation symptoms. This is particularly relevant for intensive computer work, where the pre-corneal tear film is altered resulting in dry spot formation and eye dryness, in addition to enhanced susceptibility towards sensory irritating pollutants. The workplace, thermal conditions, and work schedule (including breaks) should be planned in such a way to help maintain a normal eye blink frequency to minimize alterations of the pre-corneal tear film. The role of relative humidity on eye irritation symptoms should not be underestimated. Multiple short breaks are justified by the beneficial effect on the pre-corneal tear film. In addition, longer breaks in tasks, which require demanding visual work, should be considered. In addition, air temperature as well as certain alkene oxidation products by ozone may worsen eye irritation symptoms, but the latter factor may be smaller at higher relative humidity.     

Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation,pharmacodynamics, and percutaneous absorption mechanism

In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7?d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03?μg/g and 1.55?μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37?μg/mL. And at any time, following topical administration the mean muscle–plasma concentration ratio C_muscle/C_Plasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.     

Comparison of cytotoxicity in vitro and irritation in vivo for aqueous and oily solutions of surfactants

The in vivo model on rabbit eyes and the in vitro cytotoxicity on fibroblasts were used to compare irritation effect of aqueous and oily (Miglyol 812) solutions of surfactants. Tween 20, Tween 80 and Cremophor EL were tested in different concentrations (0.1, 1 or 5%) and the in vitro test demonstrated that surfactants in oil are less cytotoxic than in aqueous solutions. In the in vivo study, the aqueous solutions of surfactants were characterized as non-irritant while small changes in conjunctiva were observed after application the oily solutions of surfactants and the preparations were classified as slightly irritant, however this effect was similar when Miglyol was applied alone. In conclusion, it is reported that the MTT assay does not correlate well with the Draize scores.     

Formulation study of a patch containing propranolol by design of experiments

Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR).

Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2⁴ full factorial design. The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane. Finally, skin irritation was evaluated by the Draize test.

Results: N-methyl pyrrolidone (NMP) resulted as the best SPE: in addition, the critical factors influencing the PR diffusion through the human epidermis when loaded in the patch resulted in the matrix thickness (X₁, p?=?0.0957) and PR content (X₃, p?=?0.0004) which improved the flux; conversely, NMP lacked its enhancement effect when loaded in the patch and the increase in its concentration (X₄, p?=?0.006) affected the drug permeation through human epidermis. The flux of optimal formulation was 12.7?μg/cm²/h. On the basis of the steady-state concentration and clearance of PR, the estimated patch surface was 100–120 cm², since the activity of PR is related to its Senantiomer and no in vivo bioconversion occurs.

Conclusion: A patch containing (S)-PR was prepared and the (S)-PR flux (13.3?μg/cm²/h) permitted to confirm the suitability of a transdermal administration of PR. In particular, the use of a 50?μm thick methacrylic matrix containing 8% (S)-PR and 15% NMP can allow to develop a patch non-irritating to the skin, in order to ensure a constant permeation flux of PR over 48?h.