Permitted daily exposure for diisopropyl ether as a residual solvent in pharmaceuticals

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of 356 mg/m3 (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions

Spring Commencement [Program], May 17, 1980

The program of the commencement ceremonies, including a list of institutional leadership, a list of the departments by college, awards given at the ceremonies, and a list of undergraduate and graduate degree candidates.https://scholarworks.uni.edu/commencement_programs/1089/thumbnail.jp

Infortuni e malattie professionali a Taranto: una analisi dei dati INAIL

not availabl

Obiettivi, strumenti e metodi per un utilizzo epidemiologico di archivi sanitari elettronici correnti in diverse aree italiane

The availability of Electronic Health Archives (EHA) has increased remarkably over the last twenty years. As part of a joint project of the Italian Association of Epidemiology (AIE) and the Italian Association of Medical Statistics and Clinical Epidemiology (SISMEC), a workgroup of experts was set up in 2005 with the aim of comparing various experiences and of standardizing the procedures by which electronic sources can be integrated. In particular, the workgroup\u27s aim was to estimate the frequency of certain major diseases using standard algorithms applied to EHA. This volume is published with the purpose of making available in a common publication the methods and the results obtained. The results from a multicentre study using a standard approach to probabilistic record-linkage procedures are also included in a specific chapter. Eleven Italian centres from five Italian regions with an overall population of 11,932,026 collected and treated more than 21,374,426 records (year 2003) from five electronic information sources: death certificates, hospital discharge records (including outpatient discharges), drug prescriptions, tax- exemptions, and pathology records in order to estimate the frequency of the following diseases: diabetes, ischemic heart diseases, acute myocardial infarction, stroke, asthma, chronic obstructive pulmonary disease, obstructive lung diseases. For each pathology a specific algorithm was developed and used by all centres for the identification of the prevalent/incident cases of the selected diseases. Standardized methods were used to estimate the rates. The results confirm the need for a common standard approach to produce estimates based on EHA, considering the variability of the quality and of the completeness of the archives, and the difficulties of standardizing record-linkage operations in the various centres. The main achievement of this work was the elimination of the variability due to the use of different algorithms to identify cases using EHA.La disponibilit? di archivi sanitari elettronici (ASE) correnti ? andata aumentando in maniera considerevole negli ultimi due decenni. Allo scopo di confrontare le esperienze disponibili e verificare l\u27applicazione di procedure standardizzate di integrazione di ASE, nel 2005 si ? costituito un gruppo di lavoro nazionale dell\u27Associazione italiana di epidemiologia (AIE) e della Societ? italiana di statistica medica ed epidemiologia clinica (SISMEC), in particolare per definire algoritmi per la stima della frequenza di alcune delle maggiori patologie che affliggono la popolazione italiana. La produzione di questo volume nasce dalla comune decisione di rendere disponibili in maniera esauriente i risultati e i metodi utilizzati per produrre tali stime. Viene presentato inoltre uno studio per confrontare le procedure di record linkage mediante l\u27utilizzo di una tecnica probabilistica standard in diverse aree italiane. Undici centri, distribuiti in cinque regioni italiane, per una popolazione totale di 11.932.026 persone, hanno esplorato l\u27utilizzo di cinque fonti sanitarie correnti (certificati di morte, schede di dimissione ospedaliera, prescrizioni farmaceutiche, esenzioni da ticket e referti anatomopatologici) per un totale di 21.374.426 di record (anno 2003), per la stima di alcune categorie diagnostiche: diabete, cardiopatia ischemica, infarto miocardico acuto (IMA), ictus acuto, bronchite polmonare cronico-ostruttiva (BPCO), asma, malattia polmonare cronico-ostruttiva (MPCO). Sono stati elaborati e applicati algoritmi standard per identificare i casi (prevalenti/ incidenti) delle patologie studiate e sono stati standardizzati i metodi per la stima della loro frequenza. I centri partecipanti presentavano una notevole disomogeneit? nella disponibilit? temporale dei dati, nelle dimensioni e nell\u27apparente qualit? degli archivi. Non sono state riscontrate particolari difficolt? nell\u27elaborazione e nell\u27applicazione degli algoritmi patologia-specifici. I risultati delle stime di frequenza delle singole categorie diagnostiche sono commentati nei singoli capitoli di questo volume. L\u27insieme del lavoro svolto sottolinea la necessit? di adottare metodi standardizzati nell\u27utilizzo degli ASE in considerazione della variabilit? della qualit? e completezza degli archivi selezionati e della difficolt? oggettiva a standardizzare le procedure di record linkage nei vari centri. Il pregio maggiore di questo lavoro ? avere eliminato la variabilit? generata dall\u27uso di algoritmi diversi

Biopolymer production from agro-industrial wastes: bacterial strains selection and genetic improvement.

This work is included in a wider research program carried out at the Dipartimento di Agronomia Animali Alimenti Risorse Naturali e Ambiente (DAFNAE) within the EU project ANIMPOL (Biotechnological conversion of carbon containing wastes for eco‐efficient production of high added value products). The aim of the entire project was to produce high-added-value products using inexpensive agricultural by-products as carbon source. The fatty by-products from slaughterhouses have been adopted for its conversion into biopolymers such as polyhydroxyalkanoates (PHA) by properly selected and/or developed microbes. In more detail the objective of this research was to look for, select and characterise bacterial strains able to utilise, as carbon source, low cost industrial lipid wastes such as triacylglycerols (TAGs) from animal fats, with the final goal to produce PHAs. For this reason lipolytic bacteria were isolated from a variety of different environments, such as soil or waste water of a slaughterhouse. Several bacterial strains were found to possess remarkable lipolytic activities but not efficient PHAs production capabilities. As a consequence, a molecular biology program started in order to obtain a microbial strain capable of both hydrolysing lipids and producing high levels of PHAs. Delftia acidovorans DSM39, a well-known producer of PHAs with high molar fractions of 4-hydroxybutyrate (4HB), although unable to metabolize lipids, was selected as host strain. On the other hand, Pseudomonas stutzeri BT3, the most efficient lipase producer among the obtained isolates, was designated as potential donor of lipolytic genes. The lipC and lipH sequences of P. stutzeri BT3 were successfully co-expressed into D. acidovorans DSM39 and the resulting recombinant strain displayed high extracellular enzymatic activity on corn oil. The PHAs production from corn oil achieved high levels (26% of cell dry weight, with about 7% of 4HB). Surprisingly, the recombinant strain produced greater values directly from slaughterhouse residues such as udder and lard (43 and 39%, respectively, with almost 7% of 4HB). Moreover, this work proved the ability of the recombinant D. acidovorans DSM39 strain to produce PHAs with significant percentage of 4HB, without the supplementation of any precursor in the liquid broth. This research paves the way to the efficient one-step conversion of fatty residues into PHAs having valuable properties exploitable in several medical and industrial applications