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L Tollefson

Publications and source records attributed to L Tollefson.

31 records · Page 2Linked to original sources
PubMed1991

Use of epidemiology data to assess the cancer risk of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Most countries have assessed the human cancer risk of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by extrapolating from animal data. The 1600-fold variation for acceptable intakes estimated by the Americans, Canadians, and Europeans, however, indicates a large scientific uncertainty about TCDD toxicity. Regulators are attempting to use human epidemiology data to eliminate some of the limitations inherent in using animal data to quantitatively assess cancer risk in humans, particularly now that techniques for measuring TCDD levels in adipose tissue and serum are available. This paper presents an overview of the major epidemiologic studies that associate cancer with TCDD exposure. The actual exposures experienced by the study populations are emphasized. The TCDD serum levels of the Seveso, Italy, residents and of the NIOSH Dioxin Registry participants indicate that these populations hold the best promise for future assessment of the human carcinogenic risk of dioxin. Based on the animal data, however, the calculated risk from these exposures is still moderate compared with high background cancer incidence present in most industrialized countries.

Animals↗
PubMed1990

Dual-label retrograde transport: CNS innervation of the mouse thymus distinct from other mediastinum viscera.

Two different retrogradely transported tracers were identified and used to distinguish between the innervation of the thymus gland and the innervation of adjacent tissues residing within the mouse mediastinum. To determine the best procedure for peripheral dual-labeled retrograde transport, several different tracers, vehicles, and injection protocols were developed and/or tested. In the periphery, it proved ineffective to use Rhodamine latex microspheres (Luma-Fluor) as a retrograde transport agent. Horseradish peroxidase (HRP) suspended in the water-soluble carrier KY Jelly and Fluoro-Gold (FG) in an aqueous solution was the most effective combination of retrograde transport tracers. Equivalent doses of each of these tracers were determined, and injections of HRP or FG into the thymus and the esophagus produced distinct and separate patterns of labeled neurons in the spinal cord or brain stem. Throughout these CNS areas, some neurons contained both tracers suggesting that 1) these areas are innervated by neurons that give rise to collaterals to these tissues, 2) that the retrograde tracers are transported by nerves that innervate the lymphatics of the mediastinum, and/or 3) that some diffusion of the tracers occurs from the test organs and tissues to other organs and tissues of the mediastinum.

Animals↗
PubMed1990

Comparison of the cancer risk of methylene chloride predicted from animal bioassay data with the epidemiologic evidence.

Methylene chloride has been shown to be a lung and liver carcinogen in the mouse; yet, the current epidemiologic data show no adverse health effects associated with chronic exposure to this compound. Hearne et al. have compared the results of a large mortality study on occupational exposure to methylene chloride to the human risk predictions based on the rodent bioassay to point out the inconsistency between the animal toxicologic and human epidemiologic data. The maximum number of lung and liver cancers predicted due to methylene chloride exposure based on the rodent bioassay data was 24 compared to 14 deaths from these cancers actually observed in the Hearne et al. epidemiology study. We assess the minimum risk detectable by the human study in order to calculate the upperbound potency of methylene chloride and compare it to the potency derived from the bioassay data. Results from the epidemiology study imply an upperbound potency of 1.5 x 10(-2) per ppm, compared to 1.4 x 10(-2) per ppm calculated using the most conservative analysis of the animal data. We conclude that the negative epidemiology study of Hearne et al. is not sufficiently powerful to show that the risk is inconsistent with the human risk estimated by modeling the rodent bioassay data. Specifically, the doses to which the workers were exposed, the population studied, and the latency period were not adequate to determine that the risks are outside the bounds of the risk estimates predicted by low-dose modeling of the animal data.

Air Pollutants, Occupational↗
PubMed1988

Monitoring adverse reactions to food additives in the U.S. Food and Drug Administration.

Technological advances in food science have resulted in the development of numerous food additives, most of which require premarket approval by the Food and Drug Administration (FDA). Concomitant with the benefits of these additives, such as extending the shelf life of certain food commodities, is the potential for various risks. These potential risks include the possibility of the consumer experiencing an adverse reaction to the additive. In order to ascertain the character and the gravity of alleged adverse reactions to food products which it regulates, the FDA's Center for Food Safety and Applied Nutrition has developed the Adverse Reaction Monitoring System (ARMS). This postmarketing surveillance system for food additives is designed to analyze consumer reports of adverse reactions in order to alert FDA officials about any potential public health hazard associated with an approved food additive, and to delineate specific syndromes which may lead to focused clinical investigations. To date, among the products routinely monitored in the ARMS, sulfiting agents and the artificial sweetener aspartame have generated the largest volume of consumer reports describing adverse reactions. An overview of the analyses of the sulfite and aspartame adverse reaction reports is presented, along with a description of the mechanics of the postmarketing surveillance system, and a detailed discussion of its limitations.

Aspartame↗
PubMed1986

The use of epidemiology, scientific data, and regulatory authority to determine risk factors in cancer of some organs of the digestive system. 4. Colon cancer.

Colon cancer accounts for over 10% of all cancers diagnosed from 1973 to 1976 in the United States. Many factors have been identified as having a role in its etiology, including the intestinal microflora, colonic mutagens, bile acids, cholesterol, estrogens, and diet. The evidence supporting or refuting the importance of each of these factors and others is discussed. Dietary factors appear to be the most important risk determinants for colon cancer. In particular, a high-fat, low-fiber diet has been most consistently incriminated as a promoting agent of this cancer. The incidence of colon cancer and consumption of total fat and animal protein are highly correlated internationally. However, further epidemiologic studies have given equivocal results. A high-fiber diet has been proposed as being protective against colon cancer although the mechanism of protection remains unclear. A major correlational study has shown that dietary fiber consumption was higher in areas with low incidence of colon cancer than in those areas with high incidence. A few case-control studies have been supportive of the fiber hypothesis but many more have shown no difference among cases and controls in their fiber consumption. More epidemiological studies are needed to clarify the role of diet in the etiology of colon cancer. Before a dietary change is recommended, the competing risks of other cancers and other diseases should be extensively researched.

Age Factors↗
PubMed1986

Methylmercury in fish: a review of residue levels, fish consumption and regulatory action in the United States.

The dangers associated with the consumption of large amounts of methylmercury in fish are well recognized, and there is some evidence to suggest that methylmercury may be the cause of subtle neurological impairments when ingested at even low to moderate levels, particularly the prenatal and early childhood periods. This concern has prompted a continuing assessment of the risk of methylmercury toxicity among fish consumers in the United States as well as other countries. The toxicokinetics of methylmercury in humans are reviewed and used to estimate body burdens associated with toxic effects. To determine seafood consumption patterns among the continental U.S. population the Food and Drug Administration (FDA) has analyzed data from a diary study commissioned by the Tuna Research Foundation. Mercury residue levels in domestic fish sampled by the FDA were used to determine the level of exposure to methylmercury. Until evidence is presented that substantially lowers the known body burden of methylmercury which causes toxicity, calculations indicate that the current 1.0 ppm regulatory level provides adequate protection for the average fish consumer, for young children, and for a significant number of consumers exceeding the acceptable daily intake. However, additional studies are being carried out in a continuing process to ensure that safe levels of prenatal exposure to mercury residues in fish are maintained.

Animals↗
PubMed1985

The use of epidemiology, scientific data, and regulatory authority to determine risk factors in cancer of some organs of the digestive system. 2. Esophageal cancer.

The epidemiologic aspects of esophageal cancer are well known. The extreme geographical variations in incidence of the disease, the variability in the sex ratio, and the secular trends have been described frequently. The etiology of cancer of the esophagus is known to be complex and composed of multiple factors, those caused by the environment being of greatest importance. The disease preferentially attacks groups with a low socioeconomic status or those hindered by poverty. The esophageal cancer belt has been frequently studied to provide clues to the etiology of esophageal cancer but no definite culprit has yet been found. The majority of the factors so far implicated in cancer of the esophagus appear to act directly on the esophagus rather than systemically. This is an unusual situation in that it enables the disease to be prevented by primary means. There appears to be an enormous disparity in the etiology of the disease among various countries. This disparity may be more apparent than real if the epidemiologic data are interpreted to mean that there is a two-stage process involved, with multiple etiologies for each stage. If we assume that nutritional deficiencies, even subtle ones, predispose the esophagus to influence by carcinogenic substances, the geographic differences fade. Nutritional deficiencies can develop by chronic alcohol use as well as by poverty and lack of an adequate food supply, but diet does not explain the whole picture. External carcinogens are necessary to effect the end result. The culprit may be tobacco in one culture and fungal elements in another. The South African studies which showed an association with tobacco and not alcohol could be explained if we assume that the population's nutritional deficiencies already predisposed the esophagus for the effect of an external carcinogen, thereby making alcohol usage superfluous. It would be helpful if the relationship between esophagitis and nutritional status were elucidated and if it were determined that the condition could be improved or eliminated by dietary factors. The association between nutrition and esophagitis may suggest methods of primary prevention of esophageal cancer and provide a chance of lowering the incidence of this deadly disease.

Africa↗
PubMedDate not supplied

Developing new regulatory approaches to antimicrobial safety.

Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high.

Animals↗
PubMedDate not supplied

Herbicide and nutrient transport from an irrigation district into the South Saskatchewan River.

Pesticides and nutrients can be transported from treated agricultural land in irrigation runoff and thus can affect the quality of receiving waters. A 3-yr study was carried out to assess possible detrimental effects on the downstream water quality of the South Saskatchewan River due to herbicide and plant nutrient inputs via drainage water from an irrigation district. Automated water samplers and flow monitors were used to intensively sample the drainage water and to monitor daily flows in two major drainage ditches, which drained approximately 40% of the flood-irrigated land within the irrigation district. Over three years, there were no detectable inputs of ethalfluralin into the river and those of trifluralin were less than 0.002% of the amount applied to flood-irrigated fields. Inputs of MCPA, bromoxynil, dicamba and mecoprop were 0.06% or less of the amounts applied, whereas that for clopyralid was 0.31%. The relatively higher input (1.4%) of 2,4-D to the river was probably due its presence in the irrigation water. Corresponding inputs of P (as total P) and N (as nitrate plus ammonia) were 2.2 and 1.9% of applied fertilizer, respectively. Due to dilution of the drainage water in the river, maximum daily herbicide (with the exception of 2,4-D) and nutrient loadings to the river would not have resulted in significant concentration increases in the river water. There was no consistent remedial effect on herbicides entering the river due to passage of the drainage water through a natural wetland. In contrast, a considerable portion of the nutrients entering the river originated from the wetland.

Agriculture↗
PubMedDate not supplied

Antibiotic use in food animals: controlling the human health impact.

Resistance to antimicrobial drugs has compromised control of many bacterial pathogens. For foodborne pathogens, the most likely source of resistance is use of antimicrobials in food-producing animals. To control the human health impact from use of antimicrobials in animals, the U.S. Food and Drug Administration (FDA) recently announced plans to assess the microbial safety of all antimicrobials intended for use in food-producing animals. This paper describes the history of antimicrobial use and regulation in animals, the public health concern, the current animal drug approval process in the United States, the international perspective, and FDA's proposed procedures to evaluate the human health impact of the antimicrobial effects associated with animal drugs intended for use in food-producing animals. The primary public health goal of the improved regulatory paradigm is to ensure that significant human antimicrobial therapies are not lost due to use of antimicrobials in food animals.

Animals↗
PubMedDate not supplied

Food and Drug Administration surveillance of the role of foreign objects in foodborne injuries.

As part of its effort to assure a safe food supply, the Food and Drug Administration maintains a passive surveillance system for the reporting and followup of complaints related to food items. This surveillance system, called the Complaint Reporting System, records and investigates consumer complaints about the quality of a specific food item, its packaging, or unexpected effects following consumption of the food. This study, relying on data gathered from the 2,726 reports of discovery of a foreign object in a food item during fiscal year 1989, develops a profile of consumer complaints, focusing on those associated with resultant injury or illness. Fourteen percent of all reported cases of foreign object exposure cited resultant illness or injury. The most common foreign object reported in food is glass, and the most common injury is a laceration or abrasion of soft tissues of the perioral area, including the throat. There was a disproportionate representation of children younger than age 3 years with documented illness or injury. Only 3 percent of the complaints came from attending health professionals; 82 percent were self-reported. Practitioner awareness of the system is limited primarily because literature in this area is scant. The collection and investigation of reports of foreign objects in food are important because such reports provide early warnings of potential problems with manufacturers' food items. Although data suggest that severe injury from foreign object ingestion is rare, continued monitoring is warranted. Health professionals are encouraged to report such injuries through the existing system.

Food↗