Patch testing with beryllium alloy samples in guinea pigs

An experimental study was conducted in guinea pigs for the predictive assessment of the beryllium alloy hazard in occupational exposure of the skin to beryllium compounds. Guinea pigs were sensitized to beryllium sulfate according to the maximized Magnusson and Kligman test, and challenged with beryllium alloys and metallic copper, beryllium and aluminum samples. Results showed a delayed skin hypersensitivity reaction in 30 to 60% of pre-sensitized guinea pigs challenged with copper-beryllium alloys and aluminum-beryllium alloy. An inflammatory follicular reaction was induced by copper in both controls and pre-sensitized guinea pigs.     

The carcinogenic effect of a series of petroleum-derived oils on the skin of mice

Six groups of 30 Swiss mice were treated by application to the skin in the dorsolumbar region two times a week for 12 months of a "white oil" and five samples of petroleum oils derived from the same "crude" (Middle East), which were collected in the same refinery at different stages of "solvent treatment" and which form a homogeneous series with increasing concentrations of polyaromatic hydrocarbons (PAH). The macroscopic and histopathologic examination of the animals (skin and organs) up to 18 months shows the following effects with respect to the 60-mouse control group: --a marked irritating effect for the "aromatic extract," the "distillate," and a "mixture" of intermediary concentration between "distillate" and "raffinate," --a definite tumorigenic effect on the skin (papillomas, kerato-acanthomas, squamous cell carcinomas, and fibrosarcomas) of the "aromatic extract" and the "distillate." The biological answer is in significant association with the PAH concentration of the samples, which is estimated by different analytical methods: viscosity index, percentage of aromatic carbon, "total PAH" according to a gravimetric method, and benzo[a]pyrene concentration.     

Nickel allergy: tolerance to metallic surface-plated samples in nickel-sensitive humans and guinea pigs

The purpose of this work is to evaluate in nickel-sensitive patients and guinea pigs the tolerance to nickel samples, surface-plated with one or several metals of varying structures and thicknesses. All the metal samples elicited allergic reactions in the guinea pig. In humans, absolute tolerance was not observed for any sample. In humans, the interposing of a layer of bright copper between nickel and surface chrome greatly increased the tolerance.     

The analgesic efficacy of suprofen in periodontal and oral surgical pain

Suprofen is a new, orally effective nonsteroidal antiinflammatory analgesic of the propionic acid chemical class. Three separate single-dose studies were performed to evaluate the efficacy of suprofen in acute pain associated with periodontal surgery and removal of impacted third molars. Study medications were: A--suprofen 200 mg, codeine 60 mg, propoxyphene HCl 65 mg, and placebo; B--suprofen 400 mg and 200 mg, aspirin 650 mg, and placebo; C--suprofen 400 mg and 200 mg, aspirin 650 mg with codeine 60 mg, aspirin 650 mg alone, and placebo. Analgesic and side effect data were collected over a 6-hour period after patients medicated for moderate to severe pain. All studies were randomized, double-blinded, and parallel-group in design. Suprofen was significantly more effective than codeine 60 mg, propoxyphene HCl 65 mg, and aspirin 650 mg. Suprofen 400 mg appeared to be clinically more effective than the aspirin-codeine combination and the difference was statistically significant for most of the analgesic variables. Of the 224 patients who received suprofen in the 3 studies, 16 reported drowsiness and 1 reported constipation.     

Allergy to nickel or cobalt: tolerance to nickel and cobalt samples in man and in the guinea pig allergic or sensitized to these metals

The aim of this study was to evaluate, in animals and humans sensitive to nickel or cobalt, the tolerance to manufactured metal samples of nickel and cobalt of a defined metallographic structure, plated or not with a layer of chrome or copper/chrome of a determined thickness. Under the defined experimental conditions, a guinea pig sensitized to one metal (nickel or cobalt) was intolerant to both metals (nickel and cobalt). A plating of chrome or copper/chrome did not act as a protection. In the human, it was not the same: the tolerance to metal samples was determined by the specific sensitivity. A plating of chrome or copper/chrome did not act as protection.     

Nasal and pulmonary toxicity of allyl glycidyl ether in mice

A concentration-dependent expiratory bradypnea, indicative of irritation of the nasal mucosa, occurred during a 15-min oronasal exposure of mice to allyl glycidyl ether (AGE) in the concentration range of 1.9-8.6 ppm. The level of exposure responsible for a 50% decrease in the respiratory rate (RD50) was 5.7 ppm. Non-anaesthetized, tracheally cannulated mice exposed for 120 min to AGE at levels ranging from 105 to 185 ppm showed a concentration-dependent decrease in respiratory rate due to pulmonary toxicity. The level of exposure to AGE which produced a 50% decrease in the respiratory rate of tracheally cannulated mice (RD50TC) was 134 ppm. Mice were subjected to whole body exposure for 4, 9 or 14 days, 6 h/day to 7.1 or 2.5 ppm AGE. The 4-day exposure to 7.1 ppm AGE produced in the nasal cavities of mice lesions consisting of necrosis of the respiratory epithelium and complete erosion of the olfactory epithelium without pulmonary injury. Restorative responses were observed in the nasal cavities of mice exposed for 9 and 14 days to 7.1 ppm AGE. Exposure to 2.5 ppm AGE caused neither nasal nor pulmonary injury. The results indicate that AGE primarily affects the upper airways. They also make it questionable that the occupational standard of 5 ppm assures an adequate margin of protection against AGE-induced nasal effects.     

Changes in urinary proximal tubule parameters in neonatal rats exposed to cadmium chloride during pregnancy.

Pregnant Sprague-Dawley rats were injected intraperitoneally with physiological saline solution (vehicle) or cadmium chloride (CdCl2) at 2.0 or 2.5 mg kg-1 on days 8, 10, 12 and 14 of gestation. On postnatal day (PND) 3, 12 or 49, the offspring were examined for 8- or 24-h urinary excretion of beta 2-microglobulin (beta 2-m), metallothionein (MT) and urinary activity of three proximal tubular enzymes: gammaglutamyl transferase (GGT), alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG). Treatment with CdCl2 did not affect growth or survival of offspring. Significant decreases in the urinary excretion of GGT, ALP and NAG were observed on PND 3, at both doses. Exposure to 4 x 2.5 mg kg-1 resulted in functional deficit of the proximal tubule on PND 3, as evidenced by the significant increase in beta 2-m. Except for a slight but significant increase of beta 2-m in 49-day-old males, all the other urinary parameters returned to control values on PND 12. There was no effect on MT. Results from this study show that prenatal exposure to CdCl2 can induce significant changes in the kidney biochemistry of rats in the early postnatal period.     

Induced hepatotoxicity in female rats by aflatoxin B1 and ethynylestradiol interaction

Female Sprague-Dawley rats were treated with a single ip dose of aflatoxin B1 (AFB1) (3 or 6 mg/kg). Twenty-four hours later and weekly until killed, some of the rats treated with AFB1 were given ethynylestradiol (EE) by gavage at the dose of 13 mg/kg. One, three, six, and nine months following the beginning of the experiment, animals were killed. Light microscopy of liver and histochemical determinations of gamma-glutamyltransferase (GGT) as well as the measurement of hepatic drug-metabolizing enzyme activities were investigated. The results show that AFB1 induced only very weak changes in the levels of different constituents studied. Thus, the mycotoxin did not affect GGT activity and increased epoxide hydrolase activity by a maximum of 42%. In contrast, EE significantly and progressively decreased (20 to 50%) the activity of UDP-glucuronosyltransferase (UDPGT) as well as the concentration of cytochrome P-450 and microsomal proteins. However, the estrogen increased the activity of epoxide hydrolase up to 150% as well as the activity of the hepatic (400%) and plasma (175%) GGT. The results also indicate that AFB1 amplified the EE-induced increase in liver weight and enhanced the depressive effects of the estrogen on microsomal proteins, cytochrome P-450, and UDPGT. Foci of cellular alteration which consisted of clear, acidophilic and basophilic cell lesions were seen in the livers of treated rats examined by light microscopy. These lesions were more prominent in the livers of animals given combinations of AFB1 and EE; they were accompanied by a strong intensity of GGT staining in the periportal area and a marked increase of the enzyme activity in the plasma (324%). From the sixth month, the livers of some animals treated with the combinations of AFB1 and EE showed hyperplastic nodules. This study indicates that the interaction between chronic administration of EE and a single ip injection of AFB1 induces hepatic lesions considered as possible forerunners of liver cell carcinomas. It also shows that GGT is a potential marker of preneoplastic lesions and may be used, therefore, in epidemiologic surveys in humans exposed to liver carcinogens such as the aflatoxins.     

Effect of beta-naphthoflavone and phenobarbital on the nephrotoxicity of chlorotrifluoroethylene and 1,1-dichloro-2,2-difluoroethylene in the rat

The role of cytochrome P450 activity in the nephrotoxicity of chlorotrifluoroethylene (CTFE) and 1,1-dichloro-2,2-difluoroethylene (DCDFE) was investigated in the male rat. Hepatic cytochrome P450 1A1 and principally P450 2B1/2 were induced by beta-naphthoflavone and phenobarbital, respectively. Nephrotoxicity was evaluated by investigating urine biochemical parameters, kidney histochemistry and histopathological modifications. Both CTFE and DCDFE induce severe nephrotoxicity in rats after 4 h of exposure to 200 and 100 ppm, respectively. Compared with controls, activity levels of gamma-glutamyltranspeptidase (gamma GT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and N-acetyl-beta-D-glucosaminidase (NAG) in 24-h urine were increased similarly, but urinary excretion of glucose, proteins and beta2-microglobulin (beta2-m) and serum urea and creatinine levels were increased. Histopathological and histochemical examinations of kidney sections of CTFE- and DCDFE-exposed rats revealed cellular necrosis and tubular lesions 24 h after exposure. Beta-naphthoflavone-pretreated rats were afforded some protection against the nephrotoxicity of CTFE and DCDFE. Phenobarbital did not modify DCDFE nephrotoxicity but afforded some protection against CTFE nephrotoxicity. In conclusion, CTFE and DCDFE are strong nephrotoxins. Cytochrome P450 1A1 is implicated in CTFE and DCDFE metabolism and one or several cytochromes induced by phenobarbital are implicated in CTFE metabolism. The P450 cytochromes involved in CTFE and DCDFE metabolism probably constitute detoxication metabolic pathways. The nephrotoxicity of CTFE and DCDFE is therefore subordinated to the cytochrome P450 activity involved in their metabolism.