Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat.

The carcinogenic response to the combined and separate exposures to formaldehyde (HCHO) and hydrochloric acid (HCl) was investigated in male inbred SD rats. The rats were exposed to gaseous HCHO, 14 ppm, and HCl, 10 ppm, in two experiments. In one experiment the gases were premixed at high concentrations before being diluted in the exposure chamber air to maximize the formation of the carcinogen bis(chloromethyl)ether (BCME). In the second experiment exposure was repeated to HCl and HCHO premixed at high concentrations, and not premixed (to minimize BCME formation), as well as to HCHO alone and HCl alone. The second experiment is being reported on at an interim stage. HCHO alone induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl. No carcinogenic response was observed with HCl alone. HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl.

Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats.

Inhalation exposure experiments with the direct-acting alkylating agent epichlorohydrin (ECH) were done on noninbred male Sprague-Dawley rats. Single 6-hour exposure to ECH and follow-up for 14 days showed the median lethal concentration to be about 360 ppm. Further inhalation experiments were done with 6-hour exposure 5 days/week. A short-term 30-exposure regimen with 100 ppm ECH produced malignant squamous cell carcinomas of the nasal cavity in 15 of 140 rats and respiratory tract papillomas in 3 rats. Among 100 rats, lifetime exposure to 30 ppm yielded 1 malignant squamous carcinoma of the nasal cavity plus 1 nasal papilloma. No nasal or respiratory tract tumors were produced by lifetime exposure of 100 rats to 10 ppm. As controls, 100 air-treated and 50 untreated rats were used. A dose-rate effect was observed for ECH inasmuch as 30-day exposure to 100 ppm (3,000 ppm-days) produced 15 cancers in comparison to the 1 cancer from the lifetime exposure to 30 ppm (8,700 ppm-days) and no cancers from lifetime exposure to 10 ppm (2,500 ppm-days).

Myelogenous leukemia in rodents inhaling benzene.

Studies during the past five decades have failed to demonstrate myelogenous leukemia in laboratory animals exposed to benzene despite epidemiologic evidence linking such exposure to myelogenous leukemia in man. We report four cases of myeloproliferative disease among rodents exposed to benzene, 6 h a day, 5 days weekly, for life. There was one case of chronic myelogenous leukemia, one of acute myeloblastic leukemia, and one of granulocytic hyperplasia among 40 CD-1 mice exposed to 300 ppm benzene; and one case of chronic myelogenous leukemia among 40 rats exposed to 100 ppm benzene. Although not statistically significant as compared to the respective control groups, the fact that myelogenous leukemia has not been reported in control animals of these two strains is suggestive of a causative role for benzene.

Inhalation carcinogenicity of alpha halo ethers. I. The acute inhalation toxicity of chloromethyl methyl ether and bis(chloromethyl)ether.

A range of acute studies were performed with chloromethyl methyl either (CMME) and bis(chloromethyl)ether (BCME), including 14-day LC50's following single seven-hour inhalation exposures. The LC50's for CMME were 55 ppm for rats and 65 ppm for hamsters. The LC50's for BCME were 7 ppm for both species. All animals showed characteristic changes of acute irritation of the respiratory tract manifested by congestion, edema, and hemorrhage. Severe shortening of life span was seen in 30-day exposures of rats to CMME and in all studies with BCME. Incidences of mucosal changes, including atypia, were generally increased in a dose-related manner in both species. The carcinogenicity of BCME in these range finding experiments was demonstrated by a skin cancer in a rat after three exposures and a nasal tumor in a hamster after one exposure to 1 ppm BCME.

Inhalation carcinogenicity of alpha halo ethers. II. Chronic inhalation studies with chloromethyl methyl ether.

Rats and hamsters were exposed to 1 ppm of chloromethyl methyl ether six hours per day, five days per week, throughout their lifetime. Mortality and weight gain of the exposed animals paralleled that of the control animals. Malignant tumors of the respiratory tract were found in two rats. These were a squamous cell carcinoma of the lung with blood vessel invasion and an esthesloneuroepithelioma originating in the olfactory epithelium and invading the forebrain. One hamster was found to have an adenocarcinoma of the lung and another, a squamous papilloma of the trachea. A single exposed rat had a pituitary tumor of primitive cell type that may well have been coincidental.

Inhalation carcinogenicity of alpha halo ethers. III. Lifetime and limited period inhalation studies with bis(chloromethyl)ether at 0.1 ppm.

Rats and hamsters were exposed to 0.1 ppm bis(chloromethyl)ether (BCME) six hours per day, five days per week throughout their lifetime. Additional groups of rats were given 10, 20, 40, 60, 80, and 100 exposures to 0.1 ppm BCME and then held until death. Forty cancers originating in the respiratory tract were found in the 200 rats involved in these studies. These included 14 cancers of the lung and 26 cancers of the nasal cavity. They occurred in dose-related fashion. A single undifferentiated carcinoma of the lung was seen in a hamster.

[Study of the effect of arterial hypertension on the status of left- ventricular myocardium based on thallium-201 scintigraphic data]. / Vliianie arteria'lnoi gipertenzii na sostoianie miokarda levogo zheludochka po dannym stsintigrafii c 201Tl.

Functional relationship was examined between the parameters of myocardial perfusion, left ventricular myocardial mass, and complications developed in patients with coronary heart diseases concomitant with arterial hypertension. Examination was made of 102 patients with various natural history of arterial hypertension, of whom 53 had concomitant angina pectoris, myocardial infarction, congestive heart failure, sudden death, or rhythm disturbances. As "perfusion deficiency" progressed, the patients with complicated natural history of arterial hypertension were found to increase in number with higher left ventricular myocardial mass index. In patients with arterial hypertension, the critical hypertrophy phase in which the index of left ventricular myocardial mass was 110-120 gm2 was demonstrated to be followed by myocardial perfusion deficiency. If the myocardial mass index is 90 g/m2, it means a phase of compensatory hypertrophy, which shows higher myocardial perfusion.

[Use of Tl-201 in the diagnosis of parietal left-ventricular thrombi]. / Ispol'zovanie 201Tl v diagnostike pristenochnykh trombov levogo zheludochka.

The authors have proposed a method for the determination of left ventricular parietal thrombi to form isolated images of the left ventricular cavity (by the 1st passage of 201Tl) and its walls in the same projection in the computer memory. After special processing the images are superimposed: the coincidence of the contours of the cavity and myocardial wall will suggest the absence of a thrombus, noncoincidence of the contours in some place will suggest the site and size of a thrombus. The method is safe for a patient and does not require additional manipulations.

[Assessment of the diagnostic value of myocardial scintigraphy with 201Tl chloride in women of various ages]. / K otsenke diagnosticheskoi znachimosti stsintigrafii miokarda 201Tl-khloridom u zhenshchin v razlichnye vozrastnye periody.

Myocardial scintigraphy with the use of 201-thallium was performed in 92 female patients aged 38 to 87 years (initially and after 24 hours). The menstrual cycle phases were revealed to influence perfusion and metabolism of the myocardium in women with the normal ovarian cycle which should be taken into consideration in the interpretation of scintigrams in young women. The results of examining elderly persons with a long menopause have demonstrated excess saturation of scintigrams, both initial and long-term, which is primarily determined by changes in the coronary bed by the three-vascular injury type and hypertrophy of the left ventricle myocardium.

Cutaneous masking. I. Psychophysical observations on interactions of multipoint stimuli in man.

1. Psychophysical masking of cutaneous sensation at the locus of punctate test stimulation has been quantitatively examined with phasic mechanical and brief air-pulse stimuli using a conditioning-test stimulus paradigm. 2. Masking was maximal at the minimal interstimulus distance effective with this paradigm, varies inversely with interstimulus distance, and is demonstrable with the conditioning and test stimuli up to 10 cm apart on the forearm. 3. The degree of masking was found to be a direct function of the relative intensity of the conditioning stimulus with respect to the test stimulus. 4. Variations in the interstimulus interval permitted an investigation of the temporal features of cutaneous masking. It was detectable from 10 ms before to 70 ms after conditioning stimulation. Maximum masking occurred when the test stimulus was delivered about 10 ms following conditioning stimulus onset. 5. We also noted the much less marked, but still significant, enhancement phenomenon, in which weak conditioning stimuli, at just-threshold intensity levels, lowered the detection threshold for sensation at the test stimulus locus. We found this enhancement of sensation to have the same spatial distribution as did masking, but a much reduced time course. It began with the test stimulus presented simultaneously with the conditioning stimulus, peaked with 10--15 ms interstimulus intervals, but decayed in less than 40 ms. 6. Since psychophysical experiments often form the framework for the understanding of physiologic processes, it is suggested that these behavioral determinations of enhancement and masking may be correlated with the electrophysiologic properties of excitation and inhibition in neurons of the major primary somatic pathways of the central nervous system.

Cutaneous masking. II. Geometry of excitatory andinhibitory receptive fields of single units in somatosensory cortex of the cat.

1. The responses of single neurons in the primary somatosensory cortex of the cat to brief air-pulse stimuli were quantitatively examined. These controlled natural stimuli activated almost exclusively rapidly adapting hair units which, on systematic movement of the stimulus through the receptive field, gave unit-response profiles that showed the classical unimodal tent-shaped distribution. 2. Conditioning stimulus-induced inhibition of a response evoked by a fixed test stimulus was measured by systematically moving the conditioning stimulus through the receptive field. The spatial distribution of in-field inhibitory activity was unimodal and highly covariant with that of the conditioning excitation, the peak inhibition corresponding to the functional center of the excitatory receptive field. 3. Nearly one-half of the units studied evidenced inhibition extending beyond the excitatory receptive field, forming a "surround" inhibitory region; but these were usually restricted areas with rather weak inhibitory effects. 4. Time-course measuring revealed, on the average, inhibition effects measureable from 10 ms before to some 70 ms following conditioning stimulation, with peak inhibition delayed some 10--15 ms from the conditioning stimulus onset. We showed the backward inhibition, occurring with the test stimulus delivered before the onset of the conditioning stimulus, to be a property of the test response duration. Inhibition measured in the surround areas had essentially the same time course as the inhibition calculated from measurements made within the receptive fields. 5. The spatial and temporal profiles of the excitatory and inhibitory cortical unitary activity are thus very similar to the parametric features of psychophysical enhancement and masking. These findings suggest that the excitatory and inhibitory activities related to individual stimuli interact in multipoint stimulus paradigms so that simple unimodal composite profiles are synthesized.

An extractive method for determination of benzene in blood by gas chromatography.

A gas chromatographic procedure has been developed using toluene extraction for the analysis of benzene in hemolyzed blood. No sample incubation is required and only small quantities of blood (0.2 to 0.5 g) are needed. Levels as low as 0.5 mug benzene per gram of blood have been determined.

The Laskin aerosol generator.

This paper describes construction details and operating characteristics of a nebulizer developed by Sidney Laskin and used over a period of 30 yr in various laboratories to generate respirable aerosols for whole-animal inhalation exposure studies. Under the proper operating conditions, the device is capable of producing nearly monodisperse aerosols in the respirable size range (1.5 micron volume median diameter with a geometric standard deviation of 1.1) for long periods of time

An extraction method for determination of benzene in tissue by gas chromatography.

An extraction procedure has been developed for the determination of benzene by gas chromatography in tissues following inhalation. Results are reproducible using very small quanities of sample (0.05 g for tissue and 0.02 ml for blood). The procedure has been applied to the analysis of blood and tissue of A.K.R. mice following a single exposure to levels similar to those that may be found in industrial hygiene atmospheres.

[Localization of left ventricular myocardial lesions using 201Tl chloride scintigrams]. / Lokalizatsiia porazheniia miokarda levogo zheludochka po stsintigrammam s 201Tl-khloridom.

The authors propose some methodological approaches including stereometric methods, for determination of visible left ventricular walls in different projections of a gamma-chamber detector with relation to a position of the left ventricular anatomical axis (LVAA) in space to improve topographic diagnosis of left ventricular myocardial lesions with 201Tl. The above method can be implemented on computer.

Inhalation carcinogenesis by dimethylcarbamoyl chloride in Syrian golden hamsters.

The comparative carcinogenicity of dimethylcarbamoyl chloride (DMCC) was studies in male, Syrian Golden Hamsters by inhalation. Hamsters were exposed to 1ppm and the exposure periods were 6 hours per day, 5 days per week for the lifetime of the animals. Fifty-one percent of the hamsters developed carcinomas of the nasal tract. Morphologically, all of these tumors were classified as squamous cell carcinomas. In comparing the response of rats and hamsters at 1 ppm DMCC, the rat seems to show increased sensitivity and the percentage of tumor yield is almost doubled, with the tumors appearing much earlier in rats than in hamsters. However, the remarkable tumor yield in both species indicates the potent carcinogenic effects of DMCC.

Hematotoxicity of inhaled benzene to Sprague-Dawley rats and AKR mice at 300 ppm.

Sprague-Dawley rats and AKR/J mice were exposed to 300 ppm benzene vapor for 6 h/d, 5 d/wk, for life. Rats exhibited lymphocytopenia, mild anemia, and moderately decreased survival. Mice showed severe lymphocytopenia and anemia accompanied by granulocytosis and reticulocytosis. Treated mice also showed significantly decreased survival and weight gain. No indications of a leukemic or preleukemic response were observed in either species.