Evaluation of health effects

The organotins covered in this assessment have low acute toxicity to laboratory mammals, with most studies indicating LD50S above 100 mg/kg body weight, and many above 1000 mg/kg body weight. 

Short- to medium-term exposure has shown neurotoxicity, developmental toxicity, immunotoxicity, and endocrine disruption to be relevant end-points. Table 24 summarizes the critical studies for each compound and identifies NOAELs or LOAELs. The degree of each of the toxic end-points differs across the group as a whole. For example, tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

The vast majority of in vivo tests show no geno-toxicity of mono- and dialkyltins. Results from in vitro tests are variable, with little indication of DNA reactivity. There are, however, indications of clastogenicity and effects on spindle formation in mitosis in vitro. 

Brief summaries were available for unpublished long-term studies for some of the organotins under consideration. These showed no carcinogenicity for mixtures of mono- and dimethyltins in rats and mono- or 

Species Test compound End-point Concentration (mg/l) Concentration (mg organotin chloride/l) Reference 

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Eisher DR, Swint MJ, Kathren RL. 1990. Evaluation of health effects in Sequoyah Euels Corporation workers from accidental exposure to uranium hexafluoride. U.S. Nuclear Regulatory Commission, Washington D.C. NUREG/CR-5566 PNL-7328... 

Faroon O, Kueberuwa S, Smith L, and DeRosa C (1995) ATSDR evaluation of health effects of chemicals. II. Mirex and chlordecone Health effects, toxicokinetics, human exposure, and environmental fate. Toxicology and Industrial Health 11(6) 1-203. 

Various agencies have investigated substances that may be present in the environment and cause adverse effects on the environment or on human health (IPCS 1988 O Flaherty 1994 Agency for Toxic Substances and Disease Registry 1998). Chromium was one of four metals include on the priority list for the Canadian Environmental Protection Act (Meek and Hughes 1995). Speci-ation was considered to be critical in evaluation of health effects, but there was little information on exposure to individual hexavalent chromium compounds (Hughes et al. 

Koop, C. E. and Juberg, D. R., A Scientific Evaluation of Health Effects of Two Plasticizers Used in Medical Devices and Toys, www.medscape.eom/viewarticle/407990 print, 1999. Kothe, F. C. and Platmann, G. J., The Use of the Sterile Connecting Device in Transfusion Medicine, Transfusion Med. Rev., 8, 117-122, 1994. 

Kopp C E, Juberg D R, A Scientific Evaluation of Health Effects of Two Plasticizers used in Medical Devices and Toys A Report from the American Council on Science and Health, June 1999. 

C. E. Koop, D. R. Juberg, E. P. Benedek, et al. 1999. A scientific evaluation of health effects of two plasticizers used in medical devices and toys a report from the American Council on Science and Health. Medscape General Medicine, June 22, 1999. 

Another way to evaluate risks is to calculate the sensitivity of the total risk estimates to changes in assumptions, frequencies, or consequences. Risk analysts tend to be conservative in their assumptions and calculations, and the cumulative effect of this conservatism may be a substantial overestimation of risk. For example, always assuming that short-term exposure to chemical concentrations above some threshold limit value will cause serious injury may severely skew the calculated risks of health effects. If you do not understand the sensitivity of the risk results to this conservative assumption, you may misallocate your loss prevention resources or misinform your company or the public about the actual risk. 

Ovcharenko EP. 1972. An experimental evaluation of the effects of transuranic elements on reproductive ability. Health Phys 22 641. 

Health concerns about the effects of coffee are also an important consideration in coffee drinking trends. While many health issues have not been systematically and thoroughly evaluated, these concerns have undoubtedly contributed to consumption patterns. However, the most significant changes in coffee consumption occurred prior to scientific research and knowledge of health effects due to caffeine exposure. 

Health IfEa (1999) Risk assessment approaches used by UK government for evaluating Human Health Effects of Chemicals. Risk Assessment, Toxicology Steering Committee (RATSC)... 

I have been asked to discuss the human health impacts of TSCA. Any examination of such "impacts" of the Act should focus on effects that can be measured or estimated. However, in cases where the statutory goals are primarily preventive in nature, measurement or even estimation of health benefits may prove elusive. Although TSCA contains language that appears to require some consideration of the impact of regulation, it is unlikely that Congress intended that precise quantitative evaluation of the effects of TSCA be undertaken. As we shall see, such an evaluation is not feasible. 

In this paper I have tried to show that measurement of health benefits attributable to TSCA is not feasible. I hope that in doing so I have not belabored the obvious. For new chemicals and for most existing chemicals, prospective evaluation of health benefits to be achieved by various exposure controls will have to be based on extrapolation from microbial and animal data. However, while such extrapolation may be useful in a qualitative sense, quantitative risk assessment techniques involve considerable uncertainty, and in any case have not been developed for chronic effects other than cancer. 

No studies have been conducted to evaluate adverse health effects in humans or animals following exposure to endrin aldehyde or endrin ketone by the inhalation, oral, or dermal route. Additional human and animal studies via all three of these routes of potential exposure are needed to determine potential carcinogenic risk in people who may be exposed to endrin aldehyde or endrin ketone near hazardous waste sites. 

Brandt, C. S., and U. Holzel. Problems of the Recognition and Evaluation of the Effects of Gaseous Air Impurities on Vegetation. Robert A. Taft Sanitary Engineering Center Technical Report A61-37. Cincinnati U.S. Department of Health, Education, and Welfare, 1%1. 

SchaefferV. 1991. Briefing package Hazard evaluation of consumer products containing 1,4-dichlorobenzene. Washington, DC U.S. Consumer Product Safety Commission, Division of Health Effects. Directorate for Health Sciences. 

No on-going studies evaluating the health effects or toxicokinetics of fuel oils were located. 

In attempting to correlate the human and animal data, Nolan et al. (1984) validated a physiologically based pharmacokinetic model for 1,1,1-trichloroethane. The model predicted greater absorption, blood levels and metabolism of 1,1,1-trichloroethane in rodents than in humans. On the basis of toxicokinetic data, rats were suggested to be a better model than mice to evaluate potential health effects in humans. 

When evaluating the health effects of indoor air fine particulate matter, the indoor dynamics as well as the physical, chemical and biological properties of fine particles have to be considered. The indoor air fraction PM2.5 largely stems from outdoor air. Accordingly, the Ad-hoc AG also recommends WHO s (2006) 24-hour mean guideline value of 25 gg/m3 PM2.s for indoor air evaluation. In contrast to PM2.5, coarse particles (PMio) in schools, kindergartens and dwellings show much... 

Many compounds may interact and cause unexpected toxic effects which could not be expected from the known toxicity of the individual components. Often one of three principles applies for assessment of the interactions between compounds in a mixed exposure. These are (i) independent action or no interaction between the components (ii) interaction between the compounds (which in some cases may be dealt with by adding the expected effects of the individual compounds using a weight factor expressing the relative potency of the compounds) and (iii) no assessment is possible because the interaction mechanisms are too complex for normal toxicological evaluation. It should be noted that different types of health effects may require different types of assessments of the interactions and that these assessments have different accuracy. These interactions are the main causes of the slow process of establishing official guidelines of IAQ. Further information is found in Cochet et al., (2006). 

No data have been located which evaluate the health effects of radium in any of its isotopic forms in combination with any other chemicals or radionuclides. 

As is apparent from Figure 3-6, there are minimal data on health effects following dermal absorption. In addition, there were only two studies on toxicokinetics that used the dermal exposure route. Although there are several animal studies that evaluated the health effects of DEHP through the respiratory route, these studies are also limited in scope. In each case, exposures were at very low levels and without effect. Although the exposure concentrations were relevant to human exposures through inhalation, the lack of observed effects makes it difficult to evaluate whether there are specific risks that apply to respiratory exposures. 

When evaluating the health effects of barium compounds, it is important to keep in mind that different barium compounds have different solubilities in water and body fluids and therefore serve as variable sources of the Ba + ion. The Ba + ion and the soluble compounds of barium (notably chloride, nitrate, hydroxide) are generally highly toxic to humans and experimental animals. The insoluble barium compounds (notably sulfate and carbonate) are inefficient sources of the Ba + ion and therefore are generally nontoxic. Throughout the following section (2.2), the health effects by route of exposure of both soluble and insoluble barium compounds are discussed. 

U.S. Environmental Protection Agency, Office of the Testing and Evaluation. Proposed Health Effects Test Standards for Toxic Substances Control Act Test Rules, 40 CFR, Part 772, Standards for Development of Test Data sub part D- Chronic Health Effects. Fed. Reg. 44(91) 27350, 1979. 

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