5-Ethylidene-2-norbornene (ENB) is an industrial chemical whose physical properties indicate a likelihood for vapor exposure to humans. The potential for target organ or cumulative toxicity was investigated in rats exposed for 6 h per day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4- week recovery animals were added to the 14-week study. Mean analytically measured ENB vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2 ppm for the 9-day study and 4.9 +/- 0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the subchronic study. There were no mortalities, and clinical signs were limited to periocular swelling and/or encrustation, and urogenital area wetness. Body weight gain was decreased in the 9-day 359 ppm females and in the subchronic 24.8 and 149 ppm males. A minimal macrocytic anemia was present in subchronically exposed males, which resolved during the recovery period. In the 9-day study increased liver weight was associated with minimal centrilobular hepatocytomegaly and cytoplasmic basophilia with no degenerative or serum biochemical liver function changes, suggesting an adaptive response. Only relative liver weights were increased in the subchronic 149 ppm males, and no histopathological findings were observed. Principal target organ effects were to the thyroid gland, which showed an exposure concentration-related, but not exposure time-related, depletion of follicular colloid that resolved during the recovery period, together with light microscopic evidence for a hypertrophic and hyperplastic response in the follicular epithelium that resolved more slowly. The thyroid colloid depletion was a graded effect without a clear no-effect concentration, but was not accompanied by any clinical or clear biochemical evidence for thyroid dysfunction. A no-effect concentration of 4.9 ppm was established for the follicular cytological effects.

Administration, Inhalation↗

PubMedDate not supplied

The early changes in mouse skin following topical application of a range of middle distillate oil products.

A white spirit/naphtha, three kerosines, two gas oils and a catalytically cracked light cycle oil (LCO) were applied topically to mice, three times a week for up to 6 weeks, and skin changes were examined histopathologically at intervals. The changes within 1 week of treatment appeared to depend on the effect that the physicochemical properties of each type of product had on their penetration through the skin surface or via hair follicles. With white spirit the most prominent change was widespread epidermal necrosis occurring after the second treatment, implying that the lowest boiling point materials penetrate mainly through the surface epidermis. The earliest effects with kerosines were within and around hair follicles with epidermal degeneration developing later, suggesting a predominance of follicular entry. Gas oils and LCO produced similar changes to kerosines within 1 week, gas oils producing a slower and less severe response and LCO a more severe response. In skin examined after 1-6 weeks of treatment with all middle distillates, repeated cycles of necrosis and healing responses were evident; this implied that once the epidermal barrier layer had been damaged, follicular entry became less important. The severity of the skin changes observed with these middle distillates was probably sufficient for skin tumours to arise by a non-genotoxic mechanism if a similar treatment regime was used in a long-term skin painting study. A method of avoiding excessive skin irritation is therefore essential in such a study in order to obtain a reliable prediction of the human hazard of such materials.

Administration, Topical↗

PubMedDate not supplied

Mechanisms of change of panic attacks with exposure treatment of agoraphobia.

In vivo exposure homework was applied to a consecutive series of 30 outpatients suffering from DSM-IIIR panic disorder with agoraphobia. Assessment of the characteristics of panic attacks (the prodromal phase immediately preceding the attack, acute peak anxiety, and the residual phase immediately afterwards) was done by an independent rater before treatment, after six sessions and at the end of therapy (12 sessions). Twenty-five of the 30 patients completed treatment. All of them still reported panic attacks after six sessions, even though the characteristics of panic partially improved. At the end of therapy, panic attacks disappeared in 21 of the 25 patients (84%) and these gains were maintained to 1 year follow-up thereafter by the majority (81%) of subjects.

Adult↗

PubMedDate not supplied

Is dichlorvos a carcinogenic risk for humans?

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Hepatic responses to the administration of high doses of BHT to the rat: their relevance to hepatocarcinogenicity.

Although butylated hydroxytoluene (BHT) is non-mutagenic, at high doses it has recently been associated with an increased incidence of liver tumours in laboratory rodents. To establish whether chronic liver cell injury may be involved in the genesis of these tumours, BHT was administered to rats by orogastric gavage at doses of 0, 25, 250 or 500 mg/kg/day for up to 28 days and also at daily doses of 1000 and 1250 mg BHT/kg for up to 4 days (sublethal doses). The sublethal doses induced centrilobular necrosis within 48 hr, whereas administration of BHT for 7 or 28 days caused dose-related hepatomegaly and at the highest dose level induced progressive periportal hepatocyte necrosis. The periportal lesions were associated with proliferation of bile ducts, persistent fibrous and inflammatory cell reactions, hepatocyte hyperplasia and hepatocellular and nuclear hypertrophy. Biochemical changes consisted of dose-related induction of epoxide hydrolase, dose-related changes in the ratio of cytochrome P-450 isoenzymes and depression of glucose-6-phosphatase. Measurement of BHT demonstrated a dose-related accumulation in fat but not in the liver. Changes in hepatic activating and detoxifying enzyme profiles are implicated both in the mechanism of periportal hepatocyte damage and in the change of site of damage according to the dose and duration of the treatment. The persistent and active nature of the lesions in rats dosed with 500 mg BHT/kg for 28 days, combined with evidence of cell damage at doses equivalent to those associated with hepatic tumours (250 mg BHT/kg), suggests that chronic liver cell damage may be involved in their aetiology. In this and several other studies, there was no evidence that BHT causes liver damage at a dose level of 25 mg/kg/day. As this is several hundred times higher than the normal human intake, it is considered unlikely that BHT poses a threat to human health.

Adipose Tissue↗

PubMedDate not supplied

Studies on the effects of orally administered Di-(2-ethylhexyl) phthalate in the ferret.

A target-organ study of the effects of the phthalate ester di-(2-ethylhexyl) phthalate (DEHP) has been conducted in mature male albino ferrets. DEHP treatment caused a loss of body weight when administered as a 1% (w/w) diet for 14 months. Additionally marked liver enlargement with associated morphological and biochemical changes was observed. These changes consisted of liver cell enlargement, lysosomal changes, dilatation of the endoplasmic reticulum and the depression of a number of marker enzyme activities. The only other tissue observed to be affected by DEHP treatment was the testes where histological evidence of tissue damage was observed in some animals. Studies on the metabolism of [14C]DEHP in the ferret indicated that the diester was metabolised to derivatives of mono-(2-ethylhexyl) phthalate which were excreted in the urine both unconjugated and as glucuronides. The results obtained have been compared with previous studies in the rat and it is concluded that DEHP is hepatotoxic in both species.

Animals↗

PubMedDate not supplied

Early changes produced in mouse skin by the application of three middle distillates.

It has been reported by the American Petroleum Institute (API) that dermal applications of certain middle distillates of mineral oils can result in high incidences of skin tumours in mice. This was unexpected as the polycyclic aromatic hydrocarbon (PAH) levels in these were below detection limits. To examine the possible role of tissue injury in the induction of tumours, the skin reactions produced by thrice weekly applications of three middle distillates similar to those tested by the API were examined grossly and histopathologically at intervals up to 6 weeks. Various reference materials and oils were used as controls. Preliminary histological examination showed that severe skin damage was present from week 1 onwards in mice treated with the three middle distillates, two of them producing epidermal loss and ulceration. Marked epidermal hyperplasia was produced by all three middle distillates. These findings support the view that regenerative epidermal hyperplasia due to repeated severe skin damage may have exerted a powerful promotional effect in the production of the skin tumours by middle distillates in the API study.

Animals↗

PubMedDate not supplied

Predictive carcinogenicity: a model for aromatic compounds, with nitrogen-containing substituents, based on molecular descriptors using an artificial neural network.

A back-propagation neural network to predict the carcinogenicity of aromatic nitrogen compounds was developed. The inputs were molecular descriptors of different types: electrostatic, topological, quantum-chemical, physicochemical, etc. For the output the index TD50 as introduced by Gold and colleagues was used, giving a continuous numerical parameter expressing carcinogenicity. From the tens of descriptors calculated, principal component analysis enabled us to restrict the number of parameters to be used for the artificial neural network (ANN). We used 104 molecules for the study. An Rcv2 = 0.69 was obtained. After removal of 12 outliers, a new ANN gave an Rcv2 of 0.82.

Carcinogenicity Tests↗

PubMedDate not supplied

Biosynthesis of methylmercury compounds by the intestinal flora of the rat.

The contents of the rat cecum and, to a lesser extent, those of the small intestine, synthesized methylmercury from mercuric chloride labeled with Hg 203 in vitro under aerobic or anaerobic conditions. The rate of formation was approximately 18 ng/g cecal contents/20 hr. The synthesis of methylmercury was inhibited by antibiotics and by filtration of the cecal contents through membrane filters, indicating that the bacterial flora of the gut participates in the reaction. Pure cultures of bacteria, isolated from the intestinal tract of the rat, could methylate mercuric chloride. It was estimated that the total amount of methylmercury synthesized from ingested inorganic mercury in man in approximately 400 ng/day.

Anaerobiosis↗

PubMedDate not supplied

[Technology assessment and operating procedures for the technological resources in the new Community Health Service].

INTRODUCTION: The main purpose of this contribution is to set today's situation of technology assessment and point to some organizing and integrative ways with the evolution concern ASL (Local Health Firm). PATIENTS AND METHODS: We outline main critical processes that fix correct management of technological resource thought data available in national and international literature. We single out more common methods to quantify, evaluate, control and manage biomedical technologies. RESULTS: We expound decisional process that lead Viterbo ASL (Local Health Firm) to a progressive controll of tecnological resource and its management after aggregation of the five USL (Local Health Units) that constituted Viterbo ASL and describe procedures assumed. CONCLUSIONS: We underline the importance of full and complete information in business and decisional process. Inside the complexity of italian view, we outline an organizative solution with a low economic impact and with a high technical content.

Decision Making, Organizational↗