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Biomedical subjects

I C Munro

Publications and source records attributed to I C Munro.

At least 37 records · Page 2Linked to original sources
PubMed1996

Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern.

The relationship between chemical structure and toxicity was explored through the compilation of a large reference database consisting of over 600 chemical substances tested for a variety of endpoints resulting in over 2900 no-observed-effect levels (NOELs). Each substance in the database was classified into one of three structural classes using a decision tree approach. The resulting cumulative distributions of NOELs for each of the structural classes differed significantly from one another, supporting the contention that chemical structure defines toxicity. The database was used to derive a threshold of acceptable human exposure for each of the structural classes that could be applied in the absence of specific toxicity data on a substance within one of the three structural classes. The human exposure thresholds provide guidance on the degree of testing and evaluation required for substances that lack toxicity data.

Animals↗
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↗
PubMed1995

Modulators of carcinogenesis.

For decades, it has been known that a number of different factors (e.g., species, metabolism, age, animal husbandry, diet) may exhibit a significant modulating effect on the process of carcinogenesis. Often, however, these modulators have been largely uncontrolled and thus have made uncertain the results of many carcinogenicity bioassays. Fortunately, current research into molecular carcinogenesis is beginning to provide methods, not only to understand the molecular basis of known modulators of carcinogenesis, previously described only in empirical terms, but also to allow genetic modulation of carcinogenesis in experimental systems. An expanding body of knowledge regarding the role of oncogenes and tumor suppressor genes in neoplastic events is leading to a better understanding of carcinogenic mechanisms and points to the use of transgenic animal species in carcinogenicity bioassays. The transgenic animal provides methods to examine the molecular basis of carcinogenesis in experimental systems in addition to enhancing the sensitivity of carcinogen identification and the biological specificity of chemical risk extrapolation.

Age Factors↗
PubMed1995

Benzoyl peroxide: an integrated human safety assessment for carcinogenicity.

Topical benzoyl peroxide has been used in the treatment of acne for over 30 years, with no reports of adverse effects that could be related to skin carcinogenesis. Two case-control epidemiological studies have found a lack of association between the specific use of benzoyl peroxide and skin cancer. In addition to these findings in humans, 23 carcinogenicity studies in rodents with benzoyl peroxide, including 16 employing topical application, have yielded negative results. An increase in skin carcinomas was reported in 1 study in which benzoyl peroxide in acetone was applied to the skin of SENCAR mice for a 1-year period; however, this study did not employ adequate control groups to fully understand the unusual findings, and the results were inconsistent with those of 6 other similar studies. While benzoyl peroxide is not a complete carcinogen in animals and has weak or no mutagenic potential, it has been found to be a tumor promoter in mouse skin using experimental two-stage models of carcinogenesis. Consistently positive results have been obtained in tumor promotion studies in which SENCAR mice were exposed to initiating doses of potent experimental carcinogens followed by promotion with benzoyl peroxide in acetone. Negative results have been obtained in similar studies with commercial formulations. However, the results of promotion studies with benzoyl peroxide do not carry significant weight for human safety assessment as evidenced by (i) the absence of demonstrated carcinogenicity in humans of a number of rodent tumor promoters despite long-term human exposure; (ii) the observation that tumor promotion in mouse skin occurs only under specific experimental conditions and predominantly in highly sensitive strains; (iii) clinical use scenarios markedly different from the conditions resulting in tumor promotion in mouse skin; and (iv) the significant physiological differences between mouse and human skin. Thus, to date, available scientific evidence does not allow the results of these rodent promotion studies to be meaningfully applied to human safety assessment. As such, significant scientific progress must be made before human safety estimations can be derived from rodent promotion data.(ABSTRACT TRUNCATED AT 400 WORDS)

Acne Vulgaris↗
PubMed1993

Scientific principles for evaluating the potential for adverse effects from chlorinated organic chemicals in the environment.

The term chlorinated chemicals is used to describe diverse groups of chemicals of varying chemical structure, including those used in water disinfection, as well as numerous aliphatic, aromatic, and polycyclic chlorinated substances. This report elaborates a number of scientific principles that govern the evaluation of the potential for chlorinated organic chemicals to cause adverse effects on the environment and to human health. The purpose of the report is to demonstrate the importance of applying these scientific principles in the evaluation of potential adverse effects of chlorinated organic chemicals. The four major principles upon which such a scientific analysis must be based are: (1) the fate and biological activity of a compound are determined by the chemical properties of the compound; (2) compounds do not show adverse effects below certain threshold concentrations, and the magnitude of response is related to dose; (3) inherent metabolic processes allow organisms to accommodate low doses of chlorinated organic chemicals; (4) observations associated with the presence of a certain compound must be biologically plausible effects, based on the specificity of the compound's activity in experimental systems. With respect to the first of these principles, there is abundant scientific evidence that the physical and chemical properties of chlorinated organic chemicals govern their bioaccumulative potential, toxicological properties, and thus their potential behavior and effects in the environment. Chemicals that have low solubility in water are highly lipophilic and have low vapor pressure, tend to accumulate in biological systems, and degrade slowly in the environment. Chlorinated organic chemicals that possess these characteristics include those having a carbon ring structure and multiple chlorine substitution. Other chlorinated organic chemicals with lesser degrees of chlorine substitution, such as 2,4-dichlorophenoxyacetic acid (2,4-D), trichlorophenol, chloroform, and dichloroethane, do not share the physical and chemical properties of the high molecular weight, cyclic, polychlorinated compounds and, as such, do not have the same potential to bioaccumulate. These differences among chlorinated organic chemicals with respect to their physical and chemical properties and behavior in the environment preclude the generalization that all organic chemicals containing chlorine behave similarly in the environment and act as persistent, bioaccumulative chemicals. The reactivity of chlorinated organic chemicals and hence their potential to produce biological effects depends on their specific molecular features. The substitution of chlorine into an organic molecule may increase or may reduce its biological activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Generally recognized as safe (GRAS) evaluation of 4-hexylresorcinol for use as a processing aid for prevention of melanosis in shrimp.

4-Hexylresorcinol (C12H18O2) is proposed for use as a processing aid for prevention of melanosis ("black spot") in shrimp and as an alternative to the currently approved sulfites. A safety evaluation was conducted to affirm, based upon scientific procedures, the generally recognized as safe ("GRAS") status of 4-hexylresorcinol for proposed use. The GRAS safety evaluation compiled, reviewed, and analyzed data on the following areas: chemical identity, analytical methodology, historical and proposed uses, functionality, and safety. The publicly available safety data on 4-hexylresorcinol cover a broad range of potential toxicity concerns including acute and subacute toxicity, subchronic toxicity, carcinogenicity, mutagenicity, and allergenicity. These studies, along with the aforementioned data, demonstrate that 4-hexylresorcinol presents no risk of toxicity at the levels proposed for treatment of shrimp, and the use of 4-hexylresorcinol as a processing aid to prevent melanosis in shrimp is GRAS.

Animals↗
PubMed1988

Risk assessment of carcinogens: present status and future directions.

Regulatory agencies and public health authorities make extensive use of laboratory data on chemical carcinogenicity in the establishment of acceptable human exposure standards. Risk assessment practices require the quantitative extrapolation of animal data to the human setting. In this paper, the scientific assumptions underlying risk assessment are evaluated and future research needs are identified. Consideration also is given to the role of promotion assays in the evaluation of carcinogenesis and the part played by short-term tests for carcinogenicity in the regulatory process.

Animals↗
PubMed1983

Reversibility of ethylenethiourea-induced thyroid lesions.

Groups of 50 male and 50 female Sprague-Dawley rats were fed diets containing 0, 75, 100, or 150 ppm ethylenethiourea (ETU) for 7 weeks, at which time subgroups of 10 animals from each group were killed. Subsequent subgroups of 10, 10, and 20 animals were killed after an additional 2, 3, and 4 weeks, respectively, on the control diet in order to examine whether the toxicological effects induced by ETU were reversible. In both sexes, the mean body weight and feed consumption were significantly decreased in all treated groups, while the mean thyroid weight (absolute as well as relative to both body and brain weight) appeared to increase linearly with dose. Mean T4 blood levels in animals fed 150 ppm ETU were significantly below those in controls. The magnitude of the changes in body weight, thyroid weight, and T4 blood levels observed during the first 7 weeks of the study decreased after ETU was removed from the diet. The statistical procedures developed and applied here may be useful in other experiments designed to assess the reversibility of other toxicological endpoints.

Adenoma↗
PubMed1983

The power and interpretation of the carcinogenicity bioassay.

Carcinogenicity is a major consideration in the assessment of risks due to environmental chemicals. The carcinogen bioassay therefore is a very important component of the battery of toxicological tests used in hazard evaluation. The strengths and limitations of this bioassay are discussed with emphasis upon the unresolved practical considerations, the interpretation of negative results, the significance of tumors induced in the presence of a high background incidence of naturally occurring tumors, and the difficulties in transspecies extrapolation. These factors, in combination with consideration of the biological mechanisms of chemical cancer induction, will be valuable in assessing the potential risk to man posed by individual chemicals.

Animals↗