Inhalation studies in rats exposed to dimethylacetamide (DMAc) from 3 to 12 hours per day.

Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen.

Clinical response of hard tissue replacement (HTR) polymer as an implant material in oral surgery patients.

This study evaluated the performance of a synthetic implant material, Hard Tissue Replacement Polymer, for: (1) ease of handling, (2) compatibility with bone and soft tissue, (3) stability of augmentation over time, and (4) development of untoward effects. HTR (a registered trademark of HTR Sciences, a division of United States Surgical Corporation, Norwalk, CT 06856) was implanted into 34 patients by means of five different surgical procedures. The material was found to be easy to manipulate during surgery. Tissue and bone compatibility, defined as absence of inflammation, was present in 32/34 surgical sites (94%). In extraction sites during the 18-month follow-up, no measurable decrease in bone height or width was seen. One patient with a large periodontal endodontic defect developed a post-operative infection necessitating extraction of the tooth. No induction of bone was seen in response to placement of HTR material.

Large-cell lymphoma of the infratemporal fossa presenting as myofacial pain.

Patients with temporomandibular joint or myofascial pain are often subjected to rigid protocols of diagnosis and treatment. This tendency to generalize patient care can result in overlooking occult pathology. A case of large-cell lymphoma of the infratemporal fossa causing facial pain is presented.

Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats.

Male rats were exposed to 0, 110, 370, or 1100 ppm bis(2-methoxyethyl)ether (diglyme) 6 h/day, 5 days/week for 2 weeks. One group of male rats was exposed to 300 ppm 2-methoxyethanol (2-ME) for 2 weeks as a positive control. Exposed rats were killed after 10 days of exposure and 14, 42, or 84 days post-exposure (PE), respectively. At 110 ppm diglyme, spermatocytes in pachytene and meiotic division at spermatogenic stages XII-XIV were mainly affected. At 370 ppm diglyme, affected germ cells were similar to those seen at 110 ppm diglyme, but round spermatids at spermatogenic stages I-VII were also affected. The testes regained normal spermatogenesis by 84 days PE. At 1100 ppm diglyme or 300 ppm 2-ME, marked testicular atrophy was found affecting all spermatogenic stages. Damaged seminiferous tubules were lined with regenerating pachytene spermatocytes at 14 days PE and with spermatocytes and round spermatids after 42 days PE. Most but not all testes in rats exposed to 300 ppm 2-ME or 1100 ppm diglyme had normal morphology after 84 days PE. Based on the observation of germ cell damage, spermatozoa population in the epidymal tubules, reversibility of spermatogenesis after various PE periods, testicular toxicity induced by 300 ppm 2-ME was more severe than that seen at 370 ppm diglyme but was slightly less remarkable than that of 1100 ppm diglyme.

Inhalation toxicity study of formamide in rats.

Formamide is a widely used solvent for the manufacture and processing of plastics, and the possibility for inhalation exposure exists for workers. To assess the toxicity of repeated inhalation of sublethal concentrations of formamide, three groups of 10 male Crl:CD BR rats each were exposed nose-only for 6 hr/day, 5 days/week for 2 weeks to design concentrations of 100, 500, or 1500 ppm of formamide vapor in air. A control group of 10 male rats was exposed simultaneously to air only. At the end of the exposure period, blood and urine samples were collected for clinical analyses, and 5 rats per group were killed for pathologic examination. The remaining 5 rats per group were retained for a 14-day postexposure observation (recovery) period and then subjected to the same clinical and pathologic examinations. Male rats exposed to 1500 ppm had significantly depressed body weights and body weight gains during the exposure and recovery periods compared to controls. Clinical pathologic examinations revealed that decreased platelet and/or lymphocyte counts were observed in rats exposed to 500 or 1500 ppm of formamide. Pathologic examinations revealed compound-related microscopic changes in the kidneys of rats exposed to 1500 ppm formamide. Minimal to severe necrosis and regeneration of renal tubular epithelial cells were observed principally in the outer stripe of the outer medulla and in cortical medullary rays. Based upon the hematologic and clinical chemical parameters measured, the no-observed-effect exposure concentration for repeated inhalation of formamide was considered to be 100 ppm, under the conditions of this study. The findings of treatment-related microscopic lesions in the kidneys as well as increases in mean absolute kidney weights and kidney-to-body weight ratios reflect the target organ toxicity.

Acute inhalation toxicity of ammonium perfluorononanoate.

Ammonium perfluorononanoate (CAS Registry No. 4149-60-4) is a white powder that can become airborne. Its acute inhalation toxicity in male rats was studied. Male rats were exposed for single 4-hr periods to dust concentrations ranging from 67 to 4600 mg/m3. The LC50 was determined to be 820 mg/m3, with the lowest concentration causing death being 590 mg/m3. Ammonium perfluorononanoate was classified as moderately toxic by the acute inhalation route. Exposure to ammonium perfluorononanoate caused a pronounced increase in liver size. The acute toxicity of ammonium perfluorononanoate appears to be similar to that of its 8-carbon homologue, ammonium perfluorooctanoate, but considerably less than that of the 10-carbon homologue, perfluoro-n-decanoic acid.

The ultrastructure and reversibility of testicular atrophy induced by ethylene glycol monomethyl ether (EGME) in the rat.

Inhalation exposure to 300 ppm ethylene glycol monomethyl ether (EGME) for 3 days produced degenerative changes in spermatocytes of pachytene and meiotic division at spermatogenic stage XIV in rats. However, a wide range of germ cell types including spermatogonia was affected and the stage-specific damage was not discernible after 2 weeks exposure to 300 ppm EGME. The stage-specific damage was related to exposure concentration-time course. In early stages, degenerating spermatocytes showed nuclear chromatin clumping around synaptonemal complexes, cytoplasmic vesiculation with electron-dense material deposition, and disruption of the plasma membrane. Chromosomal microtubules in the meiotic division of spermatocytes were discontinued with deposition of electron-dense chromatin material. Sertoli cells showed cytoplasmic vacuolization, contact loss to germ cells, and cytoplasmic processes fragmentation with disrupted microtubules. Degenerative pachytene or meiotic spermatocytes were associated with disrupted Sertoli-germ cell relationship, chromosomal microtubules, and synaptonemal complexes. Spermatid degeneration and giant cell formation were observed after spermatocyte degeneration. Spermatid degeneration appeared to be a secondary change resulting from disrupted Sertoli-to-germ cell association. After 14 days post-exposure (PE) following 2 weeks exposure, some tubules were lined with regenerating spermatocytes with or without round spermatids. By 42 days PE, many tubules regained normal germinal epithelium, but some tubules were still atrophic even after 84 days PE. Reversibility of testicular atrophy was inversely proportional to severity of damaged stem cells.

In vivo sister chromatid exchange and micronucleus induction studies with 1,3-butadiene in B6C3F1 mice and Sprague-Dawley rats.

Male B6C3F1 mice and Sprague-Dawley rats were exposed for 2 days, 6 h/day to 1,3-butadiene (BD) by inhalation (nose only) and their bone marrow cells were evaluated for the induction of micronuclei (MN) and sister chromatid exchanges (SCEs). A significant dose-dependent increase in MN induction was observed in mice. At 100 p.p.m., the frequency of micronucleated polychromatic erythrocytes was 6-fold above control with a maximal induction of 38-fold at 10,000 p.p.m. A significant increase in SCEs was also observed in mouse bone marrow cells starting at 100 p.p.m. with a 4-fold increase over the control evident at 10,000 p.p.m. The highest tested no observed effect level for both endpoints was 50 p.p.m. In contrast, rat bone marrow cells did not exhibit significant increases in micronucleated polychromatic erythrocytes or SCEs. These results indicate that BD is genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to BD carcinogenicity.