PubMed Health⌕ Search

Biomedical subjects

D K Craig

Publications and source records attributed to D K Craig.

At least 19 recordsLinked to original sources
PubMed1999

Recommended default methodology for analysis of airborne exposures to mixtures of chemicals in emergencies.

Emergency planning and hazard assessment of Department of Energy (DOE) facilities require consideration of potential exposures to mixtures of chemicals released to the atmosphere. Exposure to chemical mixtures may lead to additive, synergistic, or antagonistic health effects. In the past, the consequences of exposures to each chemical have been analyzed separately. This approach may not adequately protect the health of persons exposed to mixtures. This article presents default recommendations for use in emergency management and safety analysis within the DOE complex where potential exists for releases of mixtures of chemicals. These recommendations were developed by the DOE Subcommittee on Consequence Assessment and Protective Actions (SCAPA). It is recommended that hazard indices (e.g., HIi = Ci/Limiti, where Ci is the concentration of chemical "i") be calculated for each chemical, and unless sufficient toxicological knowledge is available to indicate otherwise, that they be summed, that is, sigma i(n) = 1HIi = HI1 + HI2 + ... + HIn. A sum of 1.0 or less means the limits have not been exceeded. To facilitate application of these recommendations for analysis of exposures to specific mixtures, chemicals are classified according to their toxic consequences. This is done using health code numbers describing toxic effects by target organ for each chemical. This methodology has been applied to several potential releases of chemicals to compare the resulting hazard indices of a chemical mixture with those obtained when each chemical is treated independently. The methodology used and results obtained from analysis of one mixture are presented in this article. This article also demonstrates how health code numbers can be used to sum hazard indices only for those chemicals that have the same toxic consequence.

Air Pollutants↗
PubMed1992

Two-generation reproduction study of hydrotreated shale oil vapors.

Two generations of Sprague-Dawley rats were each exposed to vapors generated by countercurrent distillation (50 degrees C) at 0, 0.5, 2.5, and 5.0 mg/liter, for 6 hr/day, 5 days/week, for 124-126 days prior to mating. After mating, exposure was continuous except for the last day of gestation through lactation for F0 dams, and the last day of gestation through Day 6 of lactation for F1 dams. F1 pups were not exposed during lactation; F2 pups were exposed via nursing only. Body weights were recorded weekly before mating; organ and body weights were recorded on Days 1, 13, and 30 of gestation and on Days 1, 4, and 21 of lactation. Histopathology, reproductive performance, and certain sperm parameters were evaluated. The test material significantly (p less than 0.05) depressed body weights of F0 males and brain and lung weights of F1 weanling males at 5.0 mg/liter. Testicular weights of F1 weanling males were depressed at the 0.5 and 5.0 mg/liter concentrations. While a dose-related decrease in sperm count and sperm ATP levels and an increase in ATP/sperm ratios were observed in F0 males at 2.5 and 5.0 mg/liter, there was no adverse effect on overall reproductive performance.

Animals↗
PubMed1991

A subchronic inhalation toxicity study in rats exposed to silicon carbide whiskers.

To determine whether inhaled silicon carbide whiskers (SiC) cause lung damage in rats, four groups (50 males/50 females each) of rats were exposed to air only or to one of three concentrations of SiC 6 hr/day, 5 days/week for 13 weeks. Half (25 males/25 females/group) were euthanized at the end of exposure, the remainder 26 weeks later. Mean concentrations were 0, 630, 1746, and 7276 SiC whiskers/ml (0.09, 3.93, 10.7, and 60.5 mg/m3). Although there were no concentration-related changes in body weight, clinical chemistry, or hematological data attributable to SiC, lung weights were increased in the high concentration exposure group at both euthanization times. In all whisker-exposed groups, after 13 weeks of exposure, the incidence of the following lung and lymph node lesions was higher than in controls: inflammatory lesions; bronchiolar, alveolar, and pleural wall thickening; focal pleural fibrosis in lung; and reactive lymphoid hyperplasia in bronchial and mediastinal lymph nodes. After 26 weeks of recovery, lung inflammatory lesions had decreased and fewer rats had enlarged lymph nodes, but the incidence of alveolar wall thickening, focal pleural wall thickening, and adenomatous hyperplasia of lung had increased further. Incidence and severity appeared to be dose-related. Therefore, until longer term studies are undertaken and it is established whether the above observed lesions will progress to more severe pathological entities, it is prudent to adopt stringent handling procedures for silicon carbide whiskers.

Adenoma↗
PubMed1991

The generation and characterization of silicon carbide whiskers (fibers) for inhalation toxicology studies.

Atmospheres of silicon carbide whiskers (wh) were required for a repeated dose lung deposition study and a subchronic inhalation toxicity study, each involving exposure to three concentrations of whiskers for 6 hr/day, 5 days/week for 1 or 13 weeks. Target concentrations were 0, 500, 1500, and 7500 wh/cc. By using the mean fiber length (10 microns), diameter (0.555 micron), and density (3.2 g/cc) of the bulk material, target mass concentrations were approximately 0, 4, 12, and 60 mg/m3. The Pitt III generator, developed for cotton fiber dispersion at the University of Pittsburgh, was selected. This instrument consists of a vertical 18-in. long cylinder, which is closed at each end with rubber dams and coupled at the base to a loudspeaker. The sonic energy from the loudspeaker fluidizes the test material and the whiskers in the air column are carried out with the exhaust air. The output of the Pitt III generator was altered by changing the sound energy input, the rate of introduction of the test material into the fluidizing cylinder, or the airflow through the cylinder. Separate generation systems were used for each inhalation chamber. Chamber atmospheres were characterized gravimetrically and samples were analyzed by scanning electron microscopy. Mean mass and number concentrations for the subchronic study were 0.09, 3.93, 10.7, and 60.5 mg/m3 and 0, 630, 1746, and 7276 wh/cc, respectively. Weighted mean values for whisker diameters, lengths, and aspect ratios were 0.560 micron, 4.53 microns, and 8.62, respectively. Although whisker lengths were less than half those of the bulk material, nearly 30% of the whiskers were greater than 5 microns long.

Administration, Inhalation↗
PubMed1990

Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review.

This review evaluates the available information on the effects of mainstream and environmental tobacco smoke on the immune system in animals and humans. The primary emphasis is on mainstream smoke since little information is available on the effects of environmental smoke. The effects of mainstream tobacco smoke on the immune system in humans and animals are similar. Animals exposed to mainstream tobacco smoke for periods of a few weeks generally exhibit a slight immunostimulation. However, subchronic and chronic exposure studies indicate that immunosuppressive changes develop. Lymphocyte proliferation in response to the mitogens PHA and LPS is decreased, suggesting compromise of cell function. Antibody production can be suppressed. Smoke-exposed animals that are challenged with metastasizing tumors or viruses have been shown to exhibit a higher incidence of tumorigenic and infectious diseases, respectively. Localized immunological changes in the lung can include reduction of bronchus-associated lymphoid tissue and immunoglobulin levels. Smoking-related changes in the peripheral immune system of humans have included elevated WBC counts, increased cytotoxic/suppressor and decreased inducer/helper T-cell numbers, slightly suppressed T-lymphocyte activity, significantly decreased natural killer cell activity, lowered circulating immunoglobin titers, except for IgE which is elevated, and increased susceptibility to infection. The effects of environmental tobacco smoke on the immune system, in contrast to mainstream tobacco smoke, have just begun to be investigated and information available in the literature, to date, is limited. Immunoreactive substances are known to be present in environmental tobacco smoke, but to date, environmental tobacco smoke has been more closely associated with irritation than sensitization. A few studies have indicated a potential for environmental smoke-induced hypersensitivity and suppression of immunoregulatory substances. In contrast, other investigators have failed to detect immunological or other biological changes associated with environmental smoke. Clearly, more research is needed to resolve these differences.

Animals↗
PubMed1989

Comparative acute toxicity of shale and petroleum derived distillates.

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Alkanes↗
PubMed1987

Inhalation toxicity of ribavirin in suckling ferrets.

Ribavirin is a broad-spectrum antiviral agent useful for treatment of infants. To study the effects in developing mammalian lungs, four groups of jill ferrets and their litters were given whole body inhalation exposures for 6 h a day for 10 or 30 consecutive days to concentrations of 0 (vehicle control), 162, 355 or 620 mg/m3. The effects, including special lung observations in suckling kits, were evaluated after exposures at weaning and at puberty. First the high dose, then the mid dose jills developed lactation failure. Probably due to nutritional deficiency, approximately half of the mid dose and three quarters of the high dose kits were found dead or killed whilst moribund. There were no test compound-related deaths in the control or low dose level groups. Reductions in body weight gain were observed in both 10 and 30 day exposed kits, and high dose kits actually lost weight as exposure continued. Some recovery was apparent in survivors. Some discoloration of the liver was seen in malnourished kits at necropsy. There were no gross or histopathologic lesions in the lungs or tracheas of suckling ferrets attributable to the test material. Ribavirin exposure had no effect on the lavageable cell pool, while lung DNA to protein ratios showed a mild, reversible, proliferative response in smaller kits. There were no differences in lung function between controls and low dose kits of either group. Effects seen in the higher dose groups are due to differences in size. While there may have been a real dose-related enlargement of alveolar diameters at 40 days of age, this disappeared in males by puberty and did not seem toxicologically significant in females. The low dose, which corresponds to an exposure dose 4 to 6 times that used clinically, appeared to be a no-effect level.

Administration, Inhalation↗
PubMed1984

Subchronic inhalation toxicity of dimethylformamide in rats and mice.

Fisher F344 rats and B6C3F1 mice were exposed to concentrations of 0, 150, 300, 600 and 1200 ppm of dimethylformamide (DMF) for 6 hours a day, 5 days a week for 12 weeks. Detailed clinical observations were obtained weekly and body weights biweekly on all animals. Clinical chemistry and hematology evaluations were made on all rats and approximately half the mice at terminal sacrifice. Gross necropsy examinations were made on all animals. Histopathologic evaluations were conducted on selected tissues of animals of both species at all dose levels. Few overt signs of toxicity were seen in either rats or mice. There was a dose related depression in body weight gain in rats that was significant at the 1200 ppm level from the second week of study onwards. A total of 11 mice died or were sacrificed moribund during the study, 8 from the high dose and 2 from the 600 ppm dose level. Both clinical chemistry (in rats only) and gross necropsy observations, and histopathology of tissues indicate the possibility that liver may be the target in specific organ toxicity. The no-effect DMF dose was below the 150 ppm level for both rats and mice and the maximum tolerated dose was below the 600 ppm level.

Air Pollutants↗
PubMed1977

Chronic inhalation of cobalt oxide and cigarette smoke by hamsters.

Exposure of hamsters to CoO aerosol (10 g/L, 7 hrs./day, 5 days/week) caused pneumoconiosis but affected neither the life span nor the incidence of other than pneumoconiotic lesions. No carcinogenic effects of CoO were observed. While cigarette smoke exposures significantly increased the incidence of certain types of other than pneumoconiotic lesions including tumors, they also increased the life span of the smoke-exposed animals significantly. The latter phenomenon may account for the higher tumor incidence in the smoke-exposed animals. No effect of the smoke exposures on incidence and degree of pneumoconiosis was observed. The mean body weights of the smoke-exposed groups were significantly reduced.

Aerosols↗