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T D Jones

Publications and source records attributed to T D Jones.

At least 73 records · Page 4Linked to original sources
PubMed1988

A comparison of dose-response models for death from hematological depression in different species.

Many radiation-induced lethality experiments have been published for various mammalian species. From those studies a subset of studies reflecting useful biological and physical variables has been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic tissue was approximately uniform. The database reflects 13 mammalian species ranging in size from mouse to cattle. Some 211 studies were compiled, but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for non-rodent groups ranging from standard laboratory primates (body weight approximately 5 kg) to cattle (body weight approximately 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models include: right-skewed extreme value, left-skewed extreme value, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformation models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model.

Animals↗
PubMed1988

Chemical scoring by a rapid screening of hazard (RASH) method.

A rapid screening of hazard method (RASH) is presented for deriving relative potency estimates for hazardous substances. The method utilizes data from any available toxicological database such as the Registry of Toxic Effects of Chemical Substances (RTECS) or EPA's GENE-TOX database on genetic activity profiles. The method has been applied to derive relative potency values and permissible environmental concentrations for 278 chemicals. The derived values have been compared with recommendations of expert committees where possible, and substantial agreement is found.

Animals↗
PubMed1988

Comparison of histamine and methacholine for use in bronchial challenge tests in community studies.

Measurement of bronchial reactivity is widely used in epidemiological surveys. Histamine has been compared with methacholine inhalation challenge in two samples of adults from a small town to determine which is the better agent for use in community studies. Increasing doses of histamine and methacholine were given, up to a maximum of 4 and 12 mumol respectively, according to the method of Yan et al, the provocative dose of agonist causing a 20% fall in FEV1 (PD20) being measured. More subjects had a measurable PD20 with methacholine than with histamine, both in a random sample of 108 subjects (25 v 11 subjects, p less than 0.01) and in an additional 95 subjects selected because of wheeze in the last 12 months (67 v 48 subjects, p less than 0.01). Side effects were mild with both agents but histamine caused voice change in more subjects (21% v 11%). Repeatability was assessed in a further group of subjects with wheeze in the last year. The 95% range for a single estimation of PD20 in subjects with a measured PD20 on at least one occasion was +/- 2.5 doubling doses for histamine (n = 25) and +/- 2.1 doubling doses for methacholine (n = 33). Thus methacholine has advantages over histamine for community studies of bronchial reactivity as it is possible to use doses that produce more PD20 measurements with fewer side effects.

Adolescent↗
PubMed1985

Animal studies and prediction of human tumors can be aided by graphical sorting of animal data: neoplastic risk from B(a)P, benzene, benzidine, and chromium.

This work is a graphical study of all known dose-response data for neoplasia induced by B(a)P, benzene, benzidine, and chromium administered to test animals. Doses are put in units of lifetime intake given in micromoles of chemical per kilogram body weight, and responses are in percent increased effect per unit dose. Space limitations do not permit experiment-by-experiment critiques; however, computer graphics have been used to compare the relationship of any individual dose-response point estimate to other such point estimates for the chemical of interest. Graphics are also used to study variability resulting from different experimental parameters such as species, route of intake, number of treatments, pathological classification of neoplasia, etc. Graphical sorting, according to various physical and biological classification parameters, permits one to judge, from visual inspection, such questions as whether mice as a species are more sensitive than rats as a species, whether intravenous injection is generally more effective than inhalation, whether a single well-defined dose-response function, which ignores these classification parameters, can be evaluated numerically from the composite data base deriving from all oncogenic studies with a given chemical, etc.

Animals↗
PubMed1985

Permissible concentrations of chemicals in air and water derived from RTECS entries: a "rash" chemical scoring system.

Many chemicals are of concern to human health, but only a few have epidemiologically derived risk estimates. About 45,000 chemicals are listed in RTECS, most of which have had some testing in subhuman models. RTECS entries range from cellular effects through organoleptic damage to lethality, with many pathological endpoints listed, including mutagenic changes, irritation, teratogenesis, cancer, mortality, etc. However, it is difficult to extend any biological test results to human risk assessments. If the results are extended, the degree of validity is highly uncertain. This paper describes a logical basis for using the entire complex spectrum of test results to evaluate the overall toxicological potency of a chemical to be assayed (i.e., an interviewing chemical) and describes how to derive tentative, permissible concentrations in air and water for any particular chemical for which no regulatory guidance exists. This approach has been tested for 16 reference chemicals discussed in NIOSH Criteria Documents, EPA-CAG reports, etc. The evaluations are uncomplicated, but occasionally it is difficult to match RTECS entries for two different chemicals. Difficult comparisons may require some familiarity with experimental design and the toxicological literature. One important product of this novel approach is that a distribution or array of potency values is obtained for any chemical evaluated. This distribution reflects many uncertainties stemming from low statistical power, experimental design, pharmacological processes, interspecies variability, dose rate, biological effect monitored, route of treatment, etc. The array of relative values for a particular chemical reflects many different biological and physical conditions. The distribution of the array helps to index a composite toxicological profile for many different biological effects resulting from numerous treatment protocols. To minimize the effect of extreme sensitivity of certain (perhaps novel) biological test models, possible errors in the RTECS data-base, and possible human pharmacological insensitivity to a particular chemical and/or a particular route of administration, we consider the interquartile range (i.e., the central 50%) of the array of relative potency values between two chemicals being compared as a practical measure of uncertainty. Thus, the range in response derived from variability in relative potency should be useful in addressing the range of response in man as estimated from extrapolations of test data.

Air Pollutants↗
PubMed1984

A unifying concept for carcinogenic risk assessments: comparison with radiation-induced leukemia in mice and men.

This paper presents a new, general mathematical dose-response model which can use human, animal and cell culture data to predict the incidence of leukemia as a result of exposure to ionizing radiations. The model is based on simple considerations of fundamental biological processes of carcinogenic initiation, carcinogenic promotion and competing risk due to other toxic or disease reactions. The model can be used to predict the risk of leukemia for either human or animal populations which have been (or will be) treated with any radiation dose-time treatment protocol of interest. The model is both an extension and an outgrowth of earlier work done for the Oak Ridge dosimetry program in support activities for the Atomic Bomb Casualty Commission (formerly) and the Radiation Effects Research Foundation (currently).

Animals↗
PubMed1983

A unifying concept for carcinogenic risk assessments.

Carcinogens influence both the initiation of abnormal cells and the subsequent promotion of such cells into neoplasia. Certain other insults seem limited to the stimulation of cellular proliferation and of carcinogenic potentiation. Common examples include surgical, mechanical, chemical, and temperature wounding of tissue followed by healing. In addition, certain hyperplastic growth induced by some chemicals may also enhance tumorigenesis. We propose that the quantification of carcinogenic potentiation may derive from a common-index-quantity estimated according to enhanced cell proliferation resulting from cytotoxicity or toxic hyperplasia induced by a specific exposure. At this time, it is not possible to define, in a restrictive sense, the molecular events which are critical to potentiation but the processes of cell proliferation resulting from cytotoxicity/hyperplasia seem to serve as indices which contain the necessary (and perhaps several secondary) biological responses. The unique advantage is that cell-culture, animal, and human-level studies can be used to evaluate certain parameters of the mathematical model for an untested treatment protocol or chemical insult suspected to be a cofactor in tumorigenesis. The main thrust of this paper is to propose that tumorigenesis should be studied in terms of cellular-population kinetics in response to a biological challenge rather than according to chemical or energetic parameters of that challenge. This approach leads to mathematical equations which can serve as a unifying concept for carcinogenic risk assessments. Sample results, to illustrate the utility of this model, are given for polynuclear aromatic hydrocarbons, trace metals, ionizing radiations, CO, NO, SO2, O3, and NO2. Treatment, here, is for acute exposure conditions, but because the model is mechanistic, other exposure protocols can be addressed by simply adjusting some of the mathematical parameters according to factors estimated from a relative potency comparison of in vitro and in vivo studies best suited to the particular application of interest.

Animals↗
PubMed1976

Recurrent meningitis and labyrinthine gusher, related to congenital defects of the labyrinthine capsule and stapes footplate.

A congenital defect in the bony footplate of the stapes is now known to be a point of lowered resistance to extension of bacterial middle ear suppuration to the vestibule and thence to the meninges. Tomographic demonstration of the congenital pathologic condition of the ear permits the surgeon preoperatively to chart his surgical course. Despite antibiotic and chemotherapy, recurrent meningitis remains a serious disease as manifested by the death of two of the patients reported. The capacity for surgical correction of the congenital defect is manifested by one of our patients who has been free of meningitis for more than two years after surgery. If a congenital defect is considered in each case of recurrent meningitis, it is believed the mortality of this serious disease can be reversed.

Adult↗