Development of an Acceptable Factor To Estimate Chronic End Points From Acute Toxicity Data

1985 ◽  
Vol 1 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Bradly C. Venman ◽  
Christine Flaga

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 for an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.

2005 ◽  
Vol 10 (suppl a) ◽  
pp. 23A-26A ◽  
Author(s):  
Pierre Beaulieu

The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.


1985 ◽  
Vol 1 (4) ◽  
pp. 23-41 ◽  
Author(s):  
Michael L. Dourson ◽  
Richard C. Hertzberg ◽  
Rolf Hartung ◽  
Karen Blackburn

This paper describes two general methods for estimating ADIs that circumvent some of the limitations inherent in current approaches. The first method is based on a graphic presentation of toxicity data and is also shown to be useful for estimating acceptable intakes for durations of toxicant exposure other than the entire lifetime. The second method uses dose-response or dose-effect data to calculate lower CLs on the dose rate associated with specified response or effect levels. These approaches should lead to firmer, better established ADIs through increased use of the entire spectrum of toxicity data.


2005 ◽  
Vol 40 (4) ◽  
pp. 431-447 ◽  
Author(s):  
R. James Maguire ◽  
Suzanne P. Batchelor

Abstract A survey of water and sediment from 152 harbours, marinas and shipping channels across Canada was conducted in 1999 to determine the extent of contamination by tributyltin (TBT) prior to the total ban on its antifouling uses being phased in over the period 2003 to 2008, and to assess the effectiveness of the 1989 regulation of antifouling uses of TBT under the Canadian Pest Control Products Act. TBT was found in sediments in this survey much more frequently than in water. The main conclusion was that by 1999 the regulation had been generally effective in reducing TBT contamination in water, but not sediment, in small-craft marinas and harbours. TBT continued to be found in some freshwater and seawater locations frequented by larger vessels, that could have been legally painted at the time with TBT antifouling paints, at concentrations that could cause chronic toxicity to aquatic organisms. TBT was also found in many marine sediments, and some freshwater sediments, at concentrations that could cause chronic toxicity to sensitive benthic organisms. In addition, TBT concentrations in many marine sediments could cause acute toxicity to sensitive benthic organisms. Because of the long persistence of TBT in sediments, it may pose a hazard to benthic organisms in some locations in Canada for many years after the total ban on antifouling uses of TBT.


1996 ◽  
Vol 33 (6) ◽  
pp. 181-187 ◽  
Author(s):  
Jana Zagorc-Koncan

In recent years many waterways in Slovenia have been subjected to an increased loading with pesticides due to intensification of agriculture. The most widely used herbicides are atrazine and alachlor and they were detected in some rivers and even in ground water. Therefore the effects of atrazine and alachlor on selfpurification processes were investigated. The basic selfpurification processes studied were biodegradation of organic substances and photosynthesis and growth of algae. The inhibiting effect of pesticides on the process of biodegradation of organic pollutants was evaluated by the use of laboratory river model and mathematical modelling. The harmful impacts of pesticides on aquatic autotrophic organisms were assessed by measurement of net assimilation inhibition (24-h acute toxicity test) as well as growth inhibition - chlorophyll- a content (72-h chronic toxicity test) of algae Scenedesmus subspicatus. The results obtained demonstrate that atrazine and alachlor in concentrations found in our rivers have practically no effect on biodegrading heterotrophic organisms, while their adverse effect on algae is quite considerable.


2019 ◽  
Vol 15 (7) ◽  
pp. 685-693
Author(s):  
Arushi Jain ◽  
Pulkit Mathur

Background: Sulphites added as preservatives in food have been associated with adverse health effects in humans. Objective: The present study was designed with an objective of assessing the risk of sulphite exposure through food in adolescents (12-16 years old) of Delhi, India. Methods: A total of 1030 adolescents selected from four private and four government schools of Delhi, were asked to record their food intake using a 24 hour food record, repeated on three days, for assessing exposure to sulphites. The risk was assessed using six different scenarios of exposure. Results: The actual intake for sulphites for average consumers was 0.15 ± 0.13 mg / kg b.w. / day which was 21.4% of acceptable daily intake (ADI). For high consumers (P95), it was 65% of the ADI. However, for 2 respondents, the actual intake exceeded the ADI. The major food contributors to sulphite intake were beverage concentrates (46%), ready to serve beverages (22%) followed by miscellaneous food items (16%), mainly ice creams and snowballs. Estimation of sulphite intake using different exposure scenarios revealed that for certain scenarios where the highest reported sulphite level or maximum permissible levels were considered for calculation, the high consumers exceeded the ADI, though, for average consumers, intake was well below the ADI. Conclusion: Actual intake of sulphite for average consumers was well below the ADI but for high consumers was approaching the ADI. People with sulphite sensitivity need to be aware of hidden food sources of sulphites.


2000 ◽  
Vol 42 (3-4) ◽  
pp. 115-123 ◽  
Author(s):  
R. Shoji ◽  
A. Sakoda ◽  
Y. Sakai ◽  
M. Suzuki

The quality of environmental waters such as rivers is often deteriorated by various kinds of trace and unidentified chemicals despite the recent development of sewage systems and wastewater treatment technologies. In addition to contamination by particular toxicants, complex toxicity due to multi-component chemicals could be much more serious. The environmental situation in bodies of water in Japan led us to apply bioassays for monitoring the water quality of environmental waters in order to express the direct and potential toxicity to human beings and ecosystems rather than determinating concentrations of particular chemicals. However, problems arose from the fact that bioassays for pharmaceutical purposes generally required complicated, time-consuming, expert procedures. Also, a methodology for feedback of the resultant toxicity data to water environment management has not been established yet. To this end, we developed a novel bioassay based on the low-density lipoprotein (LDL) uptake activity of human hepatoblastoma cells. The assay enabled us to directly detect the toxicity of environmental waters within 4 hours of exposure. This is a significantly quick and easy procedure as compared to that of conventional bioassays. The toxicity data for 255 selected chemicals and environmental waters obtained by this method were organized by a mathematical equation in order to make those data much more effectively and practically useful to the management of environmental waters. Our methodology represents a promising example of applying bioassays to monitor environmental water quality and generating potential solutions to the toxicity problems encountered.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Philip J. Landrigan ◽  
Kurt Straif

Abstract Background Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. Methods To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.


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