ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00200.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00201.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The Color Additives Scientific Review Panel considered whether there was information sufficient to perform a carcinogenic risk assessment on the colors D&C Red No. 19 (R‐19), D&C Red No. 37 (R‐37), D&C Orange No. 17 (O‐17), D&C Red No. 9 (R‐9), D&C Red No. 8 (R‐8) and FD&C Red No. 3 (R‐3) and to evaluate the assessments sent to FDA as part of the petitions for use of the colors for drug and external uses by the Cosmetic, Toiletry and Fragrance Association (CTFA). There is a lack of human data concerning the colors for making a human health assessment, so the assessments are based upon the extrapolation of animal data. The risk assessments are determined for exposure to single chemicals. Excluded from consideration are possible effects from exposure to multiple chemicals, such as cocarcinogenesis, promotion, synergism, antagonism, etc. In the light of recent efforts in establishing a consensus in risk assessment, the Panel has determined that the CTFA assessments for R‐10, O‐17, and R‐9 are consistent with present acceptable usages, although it questions some of the assumptions used in the assessments. The Panel identified a number of general assumptions made, and discusses their validity, their impact on total uncertainty, and the potential options to address the gaps in understanding that necessitate the assumption. The Panel also derived revised risk estimates using more “reasonable” assumptions than “worst‐case” situations, for 90th percentile and average exposure. For those assumptions that are easily quantifiable, the Panel's estimates are less than an order of magnitude lower than the CTFA risk estimates, indicating that the underestimates and overestimates of the CTFA risk estimates tend to balance each other. The impact of most of the assumptions is not quantifiable. The assessment for R‐3 is complicated by the fact that there is no good skin penetrance study for this color. It was assumed that the penetrance is similar to that of another water‐soluble xanthene color, R‐19. It is expected that the absorption of the color is not likely to exceed that of the smaller molecule, R‐19. Therefore, the risk estimates are similar to the CTFA estimates, but with different reasoning. The estimates for R‐8 and R‐37 are different from the others in that there is a lack of any exposure or toxicological information on these colors. The toxicological properties were considered to be similar to the chemically related colors R‐9 and R‐19, respectively. The risk calculated for these dyes is actually a unit risk (i.e., a risk based on particular unit exposure). The unit exposure used is the exposure estimated from the chemically related color, which, from the production values for the dyes, is likely to have much higher usage. Exposure to all of these colors from external and drug uses is quite low, especially as a result of exposure through skin. Therefore, the risk estimates are low. It is cautioned that usage information is based on a recent survey, and ch

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00202.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

We consider animal bioassay experiments with variable dosing regimens in which groups of animals are dosed beginning at different ages and for varying durations. Two response models are discussed and then applied to data from an experiment on vinyl chloride exposure of F‐344 rats, B6C3F1 and Swiss CD‐1 mice, and Syrian Golden hamsters. The multistage model of Armitage and Doll,(1) as extended by Whittemore,(2) Day and Brown,(3) and Crump and Howe,(4) is used to estimate the dose effect on the ordered stages of tumor development. The data for all endpoints and species/strains examined consistently indicate a predominant effect on the first stage, suggesting that vinyl chloride is primarily a tumor initiator. This is consistent with evidence from two‐stage experiments on this chemical.5The second response model, new to this article, adjusts for survival nonparametrically. It is used to test for an age difference in susceptibility, to evaluate alternative exposure durations, and to compare the effectiveness of alternative dosing regimens for detecting carcinogen

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00203.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Under the assumption of multistage carcinogenesis, a multiplicative carcinogenic effect would be produced by the action of different carcinogens in a mixture on different stages of the carcinogenic process. An additive effect would be produced by the effect of different carcinogens on the same stage. A mathematical argument for these hypotheses is presented here.

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00204.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Using the most comprehensive inhalation study available, (Wagner,et al., 1974), the dose‐response effects of the four major types of asbestos fibers (amosite, anthophyllite, crocidolite, and chrysotile: Canadian, Rhodesian) for lung cancer have been determined. From linear regression analysis of the animal data and five human epidemiology studies giving a wide range of risk estimates, slopes of the curves have been determined and lifetime risk estimates made. Projected risks for rats are presented with and without surface area (s.a.) conversion factors. On the basis of cumulative exposure, the geometric mean of the point estimates for the human studies (0.0146) is quite close to the geometric mean of the animal data (0.0179 without s.a.; 0.0122 with s.a. calculations). These values also match quite well if one of the studies (McDonald,et al.) is eliminated (geometric mean = 0.031) due to qualitatively different exposure considerations (mining and milling vs. industrial environments). Animal risks based on a concentration per day basis (assuming an average 70‐year lifespan for humans) are below the lowest human estimate but within 5–6 fold (less) of the projected risk from nonsmoking asbestos workers (2.2time10‐3) using the Hammondet a

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00205.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

In the long run, molecular epidemiological techniques (1) can provide important insights for understanding a wide variety of important issues in current risk assessment and (2) are applicable across a broad spectrum of adverse effects in addition to carcinogenesis. Unfortunately, current risk assessment practices make very little use of the kind of detailed mechanistic information that molecular epidemiology can provide. Eventually, there is reason to hope that the availability of mechanistic insights provided in part by molecular epidemiology can produce some of the “essential tension” required to reform paradigms for the formulation of quantitative risk assessment models in gene

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00206.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Methods are needed to improve the ability of biomonitoring and epidemiological studies to identify potential carcinogenic hazards and to quantify human risk. The limitations of pharmacokinetic models can be mitigated by the direct measurement of molecular markers of biologically effective dose of carcinogen. Parallel animal and human studies are recommended as a means of validating these markers.

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00207.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

An attempt is made to analyze in quantitative terms the uncertainties in multiple regression estimates of the effects of air pollution on death rates. A range of factors—statistical fluctuations in numbers of deaths, differences in local age distribution, differences in smoking habits, errors in estimated pollution levels, migration, and variability of the characterization of socioeconomic effects—are assessed as potential sources of error. Both the precision and the robustness of the regression calculation are shown to be poor. Examples and illustrative calculations are given based on a study of U. K. death rates around the 1971 Cen

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00208.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The Southern California Edison Company (SCE) has instituted a series of control strategies designed to minimize human exposure to polychlorinated biphenyls (PCBs) in electrical equipment used on its system. This paper describes a method of analyzing PCB risks using conservative estimates of human intake of PCBs originating from accidental spills from electrical equipment. The PCB releases from the Edison system were determined. The fate of these releases in soil, air, and water was analyzed to determine how much material reaches human receptors. The air and water pathways were determined to be the most likely candidates for the exposure and risk considerations. PCB intake via ingestion of soil at the spill site was neglected as an exposure pathway. Equipment spills without controls resulted in at the most 2 ng/day human intake of PCBs via the water exposure pathway. This was determined to be negligible in comparison with intake rates used in conjunction with the setting of food tolerance levels based on fish being the main dietary pathway of human exposure. The inhalation exposure of the hundred or so persons in the immediate vicinity of a spill was determined to equal the PCB intakes of the fish‐eating subpopulation analyzed by the Food and Drug Administration for 2 ppm tolerance standard in the case of no controls or cleanup. Current cleanup procedures assure that even the persons in the immediate area are well below the intake of the subjects in the fish contamination analysis. All exposures were well below a “virtual safe dose” level estimated in the fish tolerance

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1986.tb00209.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY