Detection of mutagenicity of Vinclozolin and its epoxide intermediate

This study examines the potential mutagenic activity of a recently developed fungicide, Vinclozolin and its epoxide metabolite. The latter shows mutagenic activity in Schizosaccharomyces Pombe and in Salmonella Typhimurium (TA 100 strain). The same test organisms showed mutagenicity of the original compound in the presence of metabolic activation obtained with rat liver microsomes treated with various inducers

Estrogenic effect of procymidone through activation of MAPK in MCF-7 breast carcinoma cell line

Procymidone modifies sexual differentiation in vitro and induces estrogenic activity in primary cultured rainbow trout hepatocytes, as shown by an increase in the contents of vitellogenin and heat shock proteins. Since this dicarboximide fungicide is found in human tissues, it was considered of interest to investigate its ability to induce endocrine damage in the MCF-7 human cell line. The mechanism of this estrogenic action was also evaluated. Procymidone 100 (mu)M stimulated cell growth from day 3 up to day 12 and raised the level of pS2 on day 3. Although procymidone does not bind the estrogen receptor (ER), the antiestrogen ICI 182780 inhibited its effect on cell growth and pS2 content, suggesting that the ER is involved indirectly in these effects. In exploring the mechanism of ER indirect activation we found that the antibody against c-Neu receptor (9G6) did not modify procymidone's effects on cell growth and pS2 expression. Thus, procymidone does not bind the c-Neu membrane receptor, excluding this indirect ER activation pathway. We also found that procymidone induced mitogen-activated protein kinase (MAPK) at 15 and 30 min, and that PD 98059, a MAPK (Erk1/2) inhibitor, prevented procymidone's effects on cell growth and pS2, indicating that MAPK activation is responsible for procymidone ER activation. The production of reactive oxygen species (ROS) with these times and elimination of the phenomenon by (alpha)-tocopherol ((alpha)-T), a ROS scavenger, is proof that oxygen free-radical production is at the basis of the MAPK activation by procymidone

Intraocular and plasma kinetics of tenoxicam in rabbits

Non-steroidal anti-inflammatory drugs (NSAID) represent potentially useful agents in the treatment of a number of ocular pathologies, but their intraocular penetration and distribution have not yet been reported. With the aim of clarifying this point, we evaluated the concentrations of the well known NSAID, tenoxicam, in the aqueous and vitreous humors of rabbits treated i.m. with the drug (7 mg/kg). The tenoxicam kinetics in these ocular fluids followed that in plasma with the time-to-peak shifted to higher values in the vitreous (1 h) as compared to that in the aqueous and plasma (40 min). AUC was also higher in the vitreous (10.4 micrograms.h/ml) than in the aqueous humor (2.8 micrograms.h/ml)

Applicazione del D.Lgs 25/02 e definizione di "rischio moderato"

Abstract This paper describes the position of the Joint Working Group of the Italian Association of Industrial Hygienists (AIDII), the Italian Society of Occupational Health and Industrial Hygiene (SIMLII) and the Italian Society of Toxicology (SITOX) on "Analysis of Parliamentary Act D.Lgs 25/02 and role of the Scientific Societies in the definition of Limit Values". The positive aspects of the new law which implements the European Directive 98/24 are discussed, including the abolition of the rigid periodicity of medical examinations as stated by the old rule D.P.R. 303/56. The Authors also address various parts of the law which appear to be unclear and controversial and highlight the expected difficulties arising for the employers and the safety and health professionals during the application of this new piece of legislation. Moreover, a number of discrepancies are noted between the new Italian law and the original Directive or other current Italian rules such as i. the translation of the term "slight risk", as from the original Directive, into "moderate risk", and the resulting non compulsoriness of health surveillance and biological monitoring of the workers in presence of a "moderate risk", ii. the concurrent exclusion, under the same circumstances, of the occupational physician from risk assessment procedures and iii. the upward modification of the previously established (D.Lgs 277/91) occupational exposure limits for lead. Moreover, the Authors examine and criticize - both in semantic and in toxicological terms - a recent proposal for the definition of "moderate risk" made by an ad hoc Consulting Committee of the Labour Ministry, in which the term "moderate" has been interpreted either as "low" or as "irrelevant for health effects", clearly two very different meanings. Besides, it would be inappropriate to define the conditions of a moderate risk based only on the level of exposure to the chemical (expressed as a fraction of the corresponding limit value), without considering the two other components of risk assessment for that chemical (hazard and susceptibility). Even worse would be the use of simplified models based on "algorithms", which might be useful in a preliminary phase of risk assessment, but easily could lead to an under- or over-estimation of risk, particularly when used by non professionals. In conclusion, the Working Group recommend that the new law be amended in order to clarify its most controversial aspects, whose misinterpretation could severely jeopardize the protection of the workers' safety and health at work