Aromatic Amines An Assessment of the Biological and Environmental Effects (1981) / Chapter Skim
Currently Skimming:
Executive Summary
Executive Summary
Pages 1-22
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
Four aromatic amines are known to lead to ur inary tract cancer in exposed humans, and some are also responsible for the induction cuff methemoglobinemia. Some other structurally similiar amines are carcinogenic to one or more tissues in laboratory animals.
|
From page 2... ...
These exposed populations developed renal papillary necrosis and renal pelvic and bladder cancer (Bengsston et al., 1968; Rathert et al., 19731. Two consequences followed the identification of bladder carcinogens in occupationally exposed humans.
|
From page 3... ...
aliphatic amines. This report on aromatic amine s consists of chapters on the general characteristics of the class followed by chapters concerned with specif ic chemicals that illustrate problem areas .
|
From page 4... ...
, 2,4-diaminotoluene, trifluralin and oryzalin, ~cresidine, and furazolidone. Both trifluralin and furazolidone are nitro compounds, but were considered relevant to this study because of the relatively easy biological conversion of the nitro groups to the amino group and the fact that arylhydroxylamine der ivatives, in which the nitrogen is in an intermediate oxygenated state between the amine and nitro compound forms, is now generally recognized as the proximate biologically active form.
|
From page 5... ...
Because of the anticipated changes in the consumption pattern of fossil fuels -- those impl ic it in the promotion of diesel eng ines and the use of coal -- occupational and environmental exposure to the aromatic amines may increase (National Academy of Sciences, 1981~. The committee recommends that both the qualitative and |
From page 6... ...
If the metabolism of a specif ic chemical carcinogen in human tissues is qualitatively simil far to that observed in studies of tissues from a susceptible test animal, then a potential carcinogenic effect might also be observed in humans exposed to the chemical . Al though the use of humans for testing is difficult or impossible and laboratory animals tests are expensive, it should be feasible to make inferences concerning responses in humans based on In vitro tests with Truman cell lines, mutagenicity testing with human liver S-9 fractions, and careful monitoring of blood and urine of humans accidently exposed to compounds of interest.
|
From page 7... ...
Furthermore, this knowledge and the ant icipated increases in the understanding of structure-activity characteristics of aromatic amines and of other chemicals may allow for the selective development of desirable chemical species without the accompanying toxicity. CARC INOGENIC POTENCY AND RISK ESTIMATION It is not yet possible to predict the potency of a carcinogen in any species.
|
From page 8... ...
A method for expressing relative potency is described in Chapter 4. Whatever tOmor incidence-dose model is used to descr ibe a biolog ic event, the suggested means of expressing potency values discussed herein may have a considerable advantage in that these values may be derived without excessive effort or data extrapolation.
|
From page 9... ...
rubber workers have not exhibited an increased incidence of bladder cancer as a result of exposure to that compound. There is no epidemiologic evidence from which to assess the effects on humans from exposure to the specific chemicals examined in this report.
|
From page 10... ...
To determine MOCA's health effects, persons exposed occupationally to relatively high levels of MOCA, their families, and preschool children living near the plant would have to be identified, categorized as to level of current (and future ~ exposure, and followed for 20 to 40 years. The epidemiolog ic evaluation of the possible health effects from exposure to low levels of aromatic amines as well as to other substances may be costly and time consuming.
|
From page 11... ...
Mutagen ic ity tests produced negative results except in the presence of a comutagen. These findings indicate the need for fur ther research, including carcinogenic studies, possibly on dogs .
|
From page 12... ...
There is no information on the mechanism by which 2, 4-DT is activated in susceptible species, including rats and mice. Given the positive demonstration of carcinogenicity in two animal spec ies and the da ta on the genotoxic ef feats of 2, 4-Dq in In vitro systems, it is prudent to assume that humans may be under some increased risk from exposure to 2,4-DT.
|
From page 13... ...
Current manufacturing practice teas considerably reduced the level of NDPA in trifluralin and its formulations. Positive mutagenicity test results obtained with trifluralin have subsequently been attributed to a 177-ppm NDPA impurity contained in the trifluralin rather than to the test chemical itself.
|
From page 14... ...
Chronic oral exposures to E:cresidine produced bladder cancer in both male and female rats and mice as well as hepatocelluar carcinomas in male rats and female mice. In a preliminary investigation, the compound showed dose-response mutagenicity without metabolic activation in the Salmonel la assay .
|
From page 15... ...
Furazolidine has exhibited carcinogenic effects in male and female rats and mice just as other 5-nitrofurans have done. A var iety of dif ferent tissues in each species have displayed these effects.
|
From page 16... ...
First it is necessary to know which animal most closely approximates the metabol ic responses of humans. Assuming that most chemical carcinogens need to be metabolized in the host to active forms in order to exert a carcinogenic effect, it becomes necessary to know how specific carcinogens are activated in animals.
|
From page 17... ...
It would be easier to assess the potential risk to humans from many aromatic amines if additional biological data on humans were obta ined. Carcinogenic Potency and Risk Estimation More attention needs to be focused on the concepts of initiation and promotion and the inherent abilities of chemicals to act in one or the other capacity as well as in both.
|
From page 18... ...
The hemangiosarcomas and sarcomas of the spleen and other organs observed at the maximally tolerated dose (MTD) in the National Cancer In s t i tu te b ioassay need to be examined fur ther in another 1 i fet ime feeding study at three or four dose levels in a different strain of rat to interpret the signif icance of previous observations.
|
From page 19... ...
(MOCA) Tnd ividuals exposed to MOCA in Adr fan, Michigan as a result of faulty industr ial waste methods and others exposed to the compound should be studied further to learn whether or not the compound is carcinogenic in humans.
|
From page 20... ...
p-Cresidine In vitro studies of human tissues and tests with animals should be conducted to gather data on the metabolism, metabolic activation, mutagenicity, and genetic toxicity of p-cresidine. Furthermore, studies on the potential for teratogenicity and reproductive toxicity need to be performed.
|
From page 21... ...
1976. Carcinogenic aromatic amines and related compounds.
|
From page 22... ...
1976. me metabo' ism of chemical carcinogens to reactive electrophiles and their possible mechanisms of action in carcinogenesis.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.