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Biomedical subjects

R A Scala

Publications and source records attributed to R A Scala.

At least 19 recordsLinked to original sources
PubMed1997

Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats.

Groups of 110 Fischer 344 rats/sex were fed diisononyl phthalate (DINP) at dietary levels of 0, 0.03, 0.3, and 0.6 wt% for periods up to 2 years. Interim sacrifices of 10 predesignated rats/sex/dose were at 6, 12, and 18 months with surviving animals sacrificed at 24 months. At study termination, survival was in excess of 60% for every group. At the mid or high dose, the following biological effects were noted: slight decreases in food consumption and body weight; slight increase in mortality; a dose-related increase in relative organ weights of liver and kidney; and some slight effects on urinalysis, hematologic, and clinical chemistry parameters. No peroxisome induction was observed in livers of treated rats compared with controls. No clear treatment-related nonneoplastic or neoplastic lesions were found. However, mononuclear cell leukemia (MNCL) and changes known to be associated with an increased incidence of MNCL were seen in the mid-dose and high-dose groups. A literature review suggests that MNCL is a common finding in aging F344 rats and that this increased incidence in rats treated with DINP is not relevant to man. A clear no-observed-effect level was demonstrated for all biological end points at a dietary level of 0. 03 wt% or approximately 17 mg/kg/day of DINP.

Administration, Oral↗
PubMed1995

Subchronic feeding study of four white mineral oils in dogs and rats.

Subchronic 90-day feeding studies were conducted on four highly refined white mineral oils to determine any potential for toxicity in Long-Evans rats (20 per sex per dose level) and beagle dogs (4 per sex per dose level). Each oil was fed at dietary dose levels of 300 ppm and 1500 ppm (w/w). No treatment-related effects of toxicological importance were detected in daily observations of general health or in periodic assessments of food consumption and body weight, hematology, serum clinical chemistry, and urinalysis. Observations in dogs suggested that the white oils produced mild laxative effects. Gross and histopathologic examinations, as well as measurements of organ weights, did not reveal any macroscopic or microscopic changes which could be due to treatment. In addition, special staining by Oil Red O of liver, mesenteric lymph nodes, spleen, gastrointestinal tract, stomach, and kidneys indicated no evidence of oil or lipid deposition. A special re-examination of tissues from female and male rats, in response to more recent conflicting data from the Fischer 344 strain, found no histopathologic signs of macrophage accumulation and/or microgranuloma formation in liver, spleen, or mesenteric lymph nodes. These data indicate that repeated exposure to relatively high levels of white mineral oils in the diets does not produce significant subchronic toxicity in Long-Evans rats or beagle dogs.

Animals↗
PubMed1992

An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

Abnormalities, Drug-Induced↗
PubMed1990

An evaluation of the epidermal carcinogenic potential of cutting fluids.

Epidermal cancer in humans has been associated with industrial exposure to products derived from unrefined petroleum distillates. Because of this association many of these products, including cutting fluids, are now normally produced from highly refined lubricant base oils. Since highly refined oils are not dermally carcinogenic, one would predict that formulated products prepared from these oils would similarly be non-tumorigenic. However, there are experimental data that suggest that fresh cutting fluids might be dermally carcinogenic and that industrial usage might increase the carcinogenic hazard. The current studies evaluated solvent-extracted lubricant base oils and several products, including fresh and used cutting fluids and certain related industrial oils. These materials were all tested for tumorigenic potential in mouse epidermal carcinogenesis bioassays. None of the solvent-extracted lubricant base oils were dermal carcinogens. Similarly, the cutting fluids and industrial oils formulated from these base oils were not dermally carcinogenic. Finally, there was no evidence that industrial usage influenced the carcinogenic potential of these oils. It was concluded that solvent-extracted oils and the products derived from these oils pose minimal skin cancer hazards when used under appropriate conditions in industrial settings.

Animals↗
PubMed1990

Estimation of epidermal carcinogenic potency.

This report compared two statistical methods of estimating tumor latency, the Weibull distribution model and the Kaplan-Meier method. Parallelism of dose-response curves of different materials and quantitative reproducibility of dermal carcinogenesis data were also examined. The Weibull method has the advantage of producing parameter estimates, even when tumor yield is low. The Kaplan-Meier method, on the other hand, is free of distribution assumptions. Overall, since the comparisons of potency are made on the basis of parameters from the same assumed distribution on the same strain of animal, the Weibull estimates are favored. A comparison of dose-response data for benzo[a]pyrene and catalytically cracked clarified oil indicated that the slopes of the two dose-response curves were significantly different. Thus the relative carcinogenic potencies of different materials vary with dose, and potency comparisons must necessarily be dose-specific. The quantitative reproducibility of dermal carcinogenesis bioassays was also assessed. The dose-response curves from the three studies of one material had significantly different slopes. Thus the results suggested that there were sources of biological variability which could contribute to experimental error.

Animals↗
PubMed1989

A report on methods to reduce, refine and replace animal testing in industrial toxicology laboratories.

The Committee to Promote Principles of Reduction, Refinement and Replacement of Animal Testing in Industrial Toxicology Laboratories was established in 1987 to work toward industrywide improvements in laboratory animal testing methods. The committee's goals are to gather information about effective nonanimal testing techniques and other methods of conserving and improving the care of laboratory animals, to work toward the systematic validation of nonanimal alternatives, and to disseminate useful information about progressive programs and policies throughout the industrial toxicology community. This is the first in a continuing series of reports the committee plans to produce as part of an ongoing program to promote communication among industrial toxicologists about successful methods of reducing, refining and replacing animal testing. Here are some of the report's major findings: (1) Animal care and use committees charged with the oversight of laboratory animal use are a universal practice at the companies surveyed. (2) Significant reductions in the number of animals used for acute toxicity testing have taken place at all the companies during the last 5- to 10-year period. (3) Structure-activity relationships (predicting a test compound's properties based on the known properties of familiar chemicals with similar structures) are widely used to minimize, but not replace, the use of animals. (4) Tissue and organ culture systems are being used with increasing frequency for screening and mechanistic studies, but are not completely replacing animal evaluations as a final step. (5) There is a pressing need for the systematic and scientifically sound validation of nonanimal alternative techniques to reduce the use of animals in toxicology testing while satisfying requirements for the protection of public safety.

Advisory Committees↗
PubMed1988

Dermal carcinogenic activity of petroleum-derived middle distillate fuels.

In general, the carcinogenic potential of petroleum-derived materials is related to the polycyclic aromatic hydrocarbon (PAH) content. Thus it has been assumed that liquids which boil below the PAH distillation range (i.e., below approx. 370 degrees C (700 degrees F) would not be carcinogenic. Several early studies supported this conclusion but were of relatively short duration. Several recent and more rigorous studies have shown that repeated application of certain petroleum-derived materials boiling between approximately 177-370 degrees C (350-700 degrees F) (i.e., middle distillate fuels) can produce tumors in mouse skin. The current studies assessed the tumorigenic potential of a series of middle distillates which varied with respect to boiling range, composition, and source of blending stocks. All of the samples produced evidence of weak tumorigenic activity which was characterized by low tumor yields and long median latencies. However, the majority of the tumor yields were significantly different from the control. There were no apparent differences in response among the samples. Thus the various parameters examined did not substantially influence tumor outcome. In particular, there was no association of tumorigenic activity with aromatic carbon content; this finding, coupled with evidence that PAH levels were low, suggested that the tumorigenic responses were not PAH-dependent. In addition to the tumors, there was evidence of non-neoplastic dermal changes including hyperplasia. These may have contributed to the tumorigenic responses; however, the actual mechanism of tumor induction is unknown.

Administration, Cutaneous↗
PubMed1988

Motor gasoline toxicity.

The toxicology of motor gasoline is reviewed and the subject considered in two ways. First is as a problem involving a widely used commodity material and the second as a model for the study of complex mixtures. Previously reported subchronic and chronic inhalation studies showing primarily nephrotoxicity in male rats are summarized. Questions of experimental design are discussed including sample verification, species, and dose selection and choice of exposure circumstances. Low boiling, highly branched hydrocarbons primarily in the 6 to 10 carbon number range are implicated. Still unanswered is the basis for the response in male rats only and the precise mechanism of action.

Animals↗
PubMed1986

Evaluation of the dermal carcinogenic potential of tar sands bitumen-derived liquids.

The carcinogenic potential of Athabasca tar sands and six experimental liquids derived from crude bitumen was evaluated utilizing the mouse epidermal carcinogenesis model. Tar sands, bitumen, and untreated naphtha produced few, if any, tumors. Three thermally and catalytically cracked liquids, light (nominal boiling range: 149-316 degrees C) and heavy (nominal boiling range: greater than 316 degrees C) gas oils and gas oil blend (boiling range: greater than 316 degrees C), produced a significant number of epidermal neoplasms. A synthetic crude oil, prepared by blending naphtha and light and heavy gas oils, was moderately carcinogenic; however, the activity of this sample fell within the range of values obtained in studies of crude petroleum samples. Since the bitumen-derived streams do not differ substantially in carcinogenic potency from petroleum-derived materials of comparable boiling range and process history, industrial hygiene practices which limit exposures to levels comparable to those observed in the petroleum-refining industry should provide similar measures of protection.

Animals↗
PubMed1986

Occupational health aspects of unusual work schedules: a review of Exxon's experiences.

Today more than 300,000 persons in the U.S. work unusually long shifts (longer than eight hours per day) during which they are exposed to airborne toxicants. This paper reviews EXXON's experience in managing the various potential occupational health problems associated with such work schedules. A review of mathematical approaches to modifying exposure limits for such shifts is included; special emphasis is placed on the potential role of circadian rhythm effects as they serve to affect the physiological adjustment of workers to these schedules. A listing of the kinds of physical ailments which have been associated with unusual work schedules is included also. A fairly thorough list of references accompanies the text.

Adaptation, Physiological↗
PubMed1980

Benzene in the workplace.

Benzene is a major commodity chemical of great value to industry. It has long been recognized that overexposure to benzene could result in damage to the blood-forming organs of the body. More recently, it has become apparent that chronic high levels of exposure are associated with the development of leukemia. Animal experiments have also suggested that overexposure to benzene may result in certain reproductive risks.

Air Pollutants↗
PubMed1978

Toxicology: assessing the hazard.

Some of the fundamentals of toxicology that are used by the toxicologist in assessing the toxic properties of compounds have been discussed. It is easy to see that a large amount of keen professional judgment must enter into the toxicologist's decisions. It is not a job that can be done by an amateur, even though some well meaning lay and political associates may believe they are capable of doing so. The toxicologist's job is not finished when he has determined the toxicological properties of a compound. He then has to assess the hazard of the compound, an infinitely more complex and complicated task. In the end, as stated by Dr. Mrak, "There are no harmless substances, there are only harmless ways of using substances" (quoted in Reference 1, p. 11).

Animals↗