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J Doull

Publications and source records attributed to J Doull.

At least 37 records · Page 2Linked to original sources
PubMed1997

The FEMA GRAS assessment of furfural used as a flavour ingredient. Flavor and Extract Manufacturers' Association.

The Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA) has assessed the safety of furfural for its continued use as a flavour ingredient. The safety assessment takes into account the current scientific information on exposure, metabolism, pharmacokinetics, toxicology, carcinogenicity and genotoxicity. Furfural was reaffirmed as GRAS (GRASr) as a flavour ingredient under conditions of intended use based on: (1) its mode of metabolic detoxication in humans; (2) its low level of flavour use compared with higher intake levels as a naturally occurring component of food; (3) the safety factor calculated from results of subchronic and chronic studies, (4) the lack of reactivity with DNA; and (5) the conclusion that the only statistically significant finding in the 2-year NTP bioassays, an increased incidence of hepatocellular adenomas and carcinomas in the high-dose group of male mice, was secondary to pronounced hepatotoxicity. Taken together, these data do not indicate any risk to human health under conditions of use as a flavour ingredient. This evidence of safety is supported by the occurrence of furfural as a natural component of traditional foods, at concentrations in the diet resulting in a 'natural intake' that is at least 100 times higher than the intake of furfural from use as a flavour ingredient.

Adenoma, Liver Cell↗
PubMed1996

Specificity and dosimetry of toxicologic responses.

Toxicology has two goals. The first is to identify and characterize the adverse effects that can be produced in biological systems by exposure to chemicals and the second is to use this information to predict the type and severity of responses in other species and exposure situations. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, subchronic, and chronic studies in animals plus a variety of special studies designed to demonstrate specific organ damage, reproductive and teratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and other responses. These are often supplemented with studies of the kinetics and the mechanism of action and more recently with studies designed to elucidate the molecular basis for cancer and other effects. Theses studies together with the information on exposure provide the basis for subsequent toxicologic predictions. Although general effects such as weight loss and mortality are included in toxicity protocols, most of the toxicology tests are related to specific end-organ toxicity or to mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chemical sensitivity, such as depression, fatigue, headache, and memory loss, and our tests lack sufficient specificity to evaluate a syndrome which is composed primarily of such symptoms. Since all chemicals can produce adverse effects under some conditions of exposure, toxicologic predictions are most useful when they specify both the type of adverse effect anticipated and the dose required to produce the effect. Multiple chemical sensitivity does not appear to consistently involve specific chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely low levels. It is difficult to include these parameters in any reasonable toxicologic prediction relating cause and response in multiple chemical sensitivity or similar conditions.

Environmental Illness↗
PubMed1996

The FEMA GRAS assessment of alicyclic substances used as flavour ingredients.

For over 35 years, an independent panel of expert scientists has served as the primary body for evaluating the safety of flavour ingredients. This group, the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA), has achieved international recognition from the flavour industry, government regulatory bodies including the Food and Drug Administration, and the toxicology community for its unique contributions. To date, the Expert Panel has evaluated the safety of more than 1700 flavour ingredients and determined the vast majority to be "generally recognized as safe" (GRAS). Elements that are fundamental to the safety evaluation of flavour ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavour ingredients are evaluated individually taking into account the available scientific information on the group of structurally related substances. The elements of the GRAS assessment program as they have been applied by the Expert Panel to the group of 119 alicyclic substances used as flavour ingredients, and the relevant scientific data which provide the basis for the GRAS status of these substances, are described herein.

Animals↗
PubMed1996

Is it safe?

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Dose-Response Relationship, Drug↗
PubMed1993

Relative potency of chlorinated dibenzo-p-dioxins (CDDs) in acute, subchronic and chronic (carcinogenicity) toxicity studies: implications for risk assessment of chemical mixtures.

This paper shows that the relative toxic potency of four chlorinated dibenzo-p-dioxins (CDDs) is similar in two species with different sensitivities (guinea pig, Sprague-Dawley rat). More importantly, it also demonstrates that the relative toxic potencies of these homologues are very similar for acute, subchronic and chronic dosing in the same species (rat). Furthermore, examination of different endpoints of toxicity (mortality, porphyria, carcinogenicity) suggests that the dose-responses for these diverse end-points after acute, subchronic, and chronic administration are very similar if not identical for tetra-CDD. Based on toxicokinetic and toxicodynamic considerations, a new, possibly generalizable rule (average tissue concentration x time = toxicity) is derived for CDDs. Implicit in the relative potency arguments of CDDs is the requirement of a practical threshold dose for all endpoints of toxicity including cancer.

Administration, Oral↗
PubMed1993

Designing a biological monitoring program to assess community exposure to chromium: conclusions of an expert panel.

The possible benefits of biological monitoring of large groups of people potentially exposed to environmental contaminants has become an area of much interest in recent years. Because chromite-ore processing residue has been found in some soils in northern New Jersey, urinary chromium monitoring of people in the community was evaluated as a potentially useful tool. In an attempt to identify those who could be exposed and to quantify the magnitude of exposure to the chromium in these soils, the New Jersey Department of Health (NJDOH) initiated a public health screening project. In 1992, the NJDOH proposed to evaluate over 4000 people who lived or worked near these sites. Volunteers were administered a questionnaire and were given a limited physical examination, and a single spot urine sample was collected. Because of the difficulties in using urinary chromium to assess low-level exposure and the potential implications of any regulatory decisions that could be based on the results of this project, a panel of experts was convened to evaluate the protocol. The panel consisted of five scientists and physicians with expertise in toxicology, dermatology, epidemiology, biological monitoring, and analytical chemistry. Like a World Health Organization group, the panel concluded that although urine biomonitoring can be useful in evaluating high levels of exposure to chromium, it is not reliable for assessing low-level exposure similar to that which may have occurred in northern New Jersey. The panel also noted that when urinary biomonitoring is to be used to assess the public's possible exposure, a large number of precautions must be taken to ensure the accuracy and usefulness of the results. The single most important recommendation was to collect a second, and perhaps a third, spot urine (or 24-h urine) sample before concluding that a person may be routinely overexposed. These suggestions are applicable to designing a biomonitoring program for nearly any environmental contaminant to which a community may be exposed. A review of scientific literature associated with biological monitoring of chromium is provided.

Absorption↗
PubMed1992

Global estimates of acute pesticide morbidity and mortality.

Mathematical models have projected increasing numbers of pesticide poisoning throughout the world, rising from 500,000 cases/yr in 1972 to 25,000,000 cases/yr in a 1990 estimate. Among 148 outbreaks (excluding Bhopal and three probable epidemics of pesticide-related suicide) reported between 1951-90, the known number of cases was 24,731 with 1065 deaths (4.3% case fatality); these are probably underestimates. Among the known outbreaks, the most commonly identified agents were organophosphates (58), carbamates (23), chlorinated hydrocarbons (23), and organic mercurials (11). Food was the most common vehicle of exposure in these epidemics (83 outbreaks), followed by skin contact (26), multiple types of exposure (22), and respiratory exposure (16). Two countries, the United States and Thailand, accounted for more than half the reports. Both the mathematical models and the outbreak investigations support the need for continuing investigation and improved surveillance throughout the world.

Accidents↗
PubMed1992

Alcohol and cancer.

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Alcohol Drinking↗
PubMed1991

GRAS evaluation of flavoring substances by the Expert Panel of FEMA.

The review describes the evolution of the process of GRAS evaluation of flavoring substances by the Expert Panel of FEMA during the past 30 years. These materials possess prominent olfactory and gustatory effects and, therefore, are added to foods in very small quantities. The procedures used and criteria employed for GRAS determinations are noted. Attention is called to the process for the re-review of the GRAS status of flavoring substances.

Animals↗
PubMed1987

The mouse in safety evaluation.

Several recent publications have reviewed the history, rationale and experience concerning the use of mice as a test species in oncogenicity bioassay programs. Conclusions from three of these publications will be discussed: The Report of the International Expert Advisory Committee on the Relevance of Mouse Liver Hepatoma to Human Carcinogenic Risk (from the Nutrition Foundation), the Report of the NTP Ad Hoc Panel of Chemical Carcinogenesis Testing and Evaluation (from the Board of Scientific Counselors of the National Toxicology Program), and Chemical Carcinogens: Review of the Science and its Associated Principles (from the Office of Science and Technology Policy). Using the recommendations from these and other groups regarding modification of the current testing protocols and alternative approaches to evaluating the adverse health effects of long-term, low-level exposure to environmental chemicals, an effort will be made to predict some future developments in this area of toxicology.

Animals↗
PubMed1985

Isolation and characterization of Streptomyces venezuelae mutants blocked in chloramphenicol biosynthesis.

Twelve Streptomyces venezuelae mutants blocked in chloramphenicol biosynthesis were isolated. Two of these (Cm1-1 and Cm1-12) were apparently blocked in the conversion of chorismic acid to p-aminophenylalanine and three (Cm1-4, Cm1-5 and Cm1-8) accumulated p-aminophenylalanine and may have been blocked in the hydroxylation reaction that converted this intermediate to p-aminophenylserine. One mutant (Cm1-2) accumulated D-threo-1-p-nitrophenyl-2-propionamido-1,3-propanediol and D-threo-1-p-nitrophenyl-2-isobutyramido-1,3-propanediol, indicating that chlorination of the alpha-N-acyl group of chloramphenicol was blocked. The remaining six strains did not excrete any detectable chloramphenicol pathway intermediates.

Chloramphenicol↗