Topical exposure, toxic effects

IPCS Environmental Health Criteria Documents reflect the collective view of an international group of experts and do not necessarily represent the decision or stated policy of UNEP, ILO, or WHO. The reports summarize and interpret the pertinent published literature. Unpublished information is used when published information is absent or when data are pivotal to the risk assessment. Adequate human data are preferred to animal data. Topics include physical chemistry sources of exposure environmental fate and transport concentrations in the environment and in humans pharmacokinetics effects from acute, subacute, and long-term exposure toxic effects on skin, eye, and reproduction mutagenesis and cancer. 

Only a few in vivo dermal toxicity studies have been reported so far. Huczko and Lange [50] evaluated the potential of raw CNTs to induce skin irritation by conducting two routine dermatological tests (patch test on 40 volunteers with allergy susceptibilities and Draize rabbit eye test on four albino rabbits). Koyama etal. [51] showed the biological responses to four different types of carbon nanotubes (SWNTs, two types of MWNTs with different diameters, and cup-stacked carbon nanotubes) after their subcutaneous implantation in mice. Both tests [50, 51] showed no or poor irritation effects. However, the in vitro studies in epidermal cell lines exposed to CNTs, and also a more recent report on the toxic outcomes of topical exposure of mice to SWNTs [46], have raised concerns over these assessments. Clearly, this is an area requiring further scientific evaluation. 

Toxic effects of expositions are calculated for a variety of exposures and effect combinations, assuming a probabilistic dose-effect relationship. Lethal and incapacitating responses (e.g. respiratory effects, topical skin effects or incapacitating eye effects) of varying degrees of severity are addressed. The model also distinguishes between effects resulting from vapour exposure and from exposures to liquid droplets. These primary effect probabilities are subsequently combined to afford overall casualty probabilities for lethality, severe incapacitation and incapacitation due to topical eye effects. 

Dermal Effects. No reports are available on the toxicity of chloroform to skin after inhalation and oral exposures in humans. Stratum comeum damage was reported after a topical exposure of chloroform of 15 minutes duration for 6 consecutive days (Malten et al. 1968). Chloroform was used as a vehicle for the topical application of aspirin for the treatment of painful herpes zoster lesions in male and female humans. The only reported side-effect was an occasional burning sensation to the skin as the chloroform evaporated after application (King 1993). 

In a follow-up study in mice, exposure to DEA, via drinking water or by topical application, caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myoqn e degeneration), and skin (site of application ulceration, inflammation, hyperkeratosis, and acanthosis). Doses ranged from 630 to 10,000 ppm in the drinking water and from 80 to 12 50 mg/kg in the topical application study. 

Whether adverse health effects result from exposure to mercury from amalgams at the levels reported above is currently a topic of on-going research and considerable discussion. A thorough review of this subject is beyond the scope of this profde. Readers are referred to the end of this section (see More on the Effects of Dental Amalgam) for a discussion of some recent reviews of this topic, and a few examples of studies on the putative toxic effects or the lack thereof from continued use of amalgam. 

The scientific issues associated with understanding and estimating human exposures to chemicals in the environment are vastly more complicated than has been suggested in this chapter, but for present purposes they have been covered sufficiently. The primary purpose of the discussion is to introduce some terms that will come up frequently in later chapters, and to provide some insight regarding how scientists come to understand how much of which chemicals are present in environmental media, and some of the ways they can come to enter the human body. At this point we are coming close to the central topic of toxicity, which obviously cannot occur until chemicals actually contact various parts of the body. But there is one more step that needs to be examined before toxic effects are considered. How do chemicals enter, move around within, and exit the body ... 

Recognizing the fact that ROS play a role in the pathogenesis of mustard-induced ocular injuries, compounds that inhibit the formation of ROS or prevent their toxic effects would be beneficial in the treatment of mustard-induced ocular injuries. The topical application of low concentrations of Zn/DFO or Ga/DFO after comeal exposure to nitrogen mustards markedly reduced conjunctival, comeal, iris, and anterior chamber injury. In the cornea, the healing of epithehal erosions was faster, the long-term opacification was reduced, and the levels of neovascularization were lowered. In the anterior chamber, decreased inflammation and better maintenance of intraocular pressure were achieved. Cataractous changes were also notably milder (Banin et al., 2003). 

Risk assessments have been performed for a variety of topics, from accidents in the workplace, to lifestyle choices and natural catastrophes. This chapter will focus on evaluating human risk primarily from chemical and radiological exposure. Risk assessment as defined by the National Academy of Science is the use of the factual base to define the health effects of exposure of individuals or populations to hazardous materials and situations. Risk assessment determines if a chemical has a toxic effect, estimates the exposure to this chemical and identifies the adverse effects of the chemical. The combination of the toxicity influenced by the level of exposure estimates what the... 

Topical Exposure. Dosing of female house fly females with five monoterpenoids yielded toxic effects when applied alone at high doses. d-Limonene was the most active of the five (Table I). Use of the synergist piperonyl butoxide enhanced the activity of d-limonene, pulegone, and linalool considerably, by 17, 21, and >14 fold, respectively. These results indicate that those three terpenoids insecticidal activity is expressed more fully when the oxidative detoxification process is inhibited. It is not surprising that flies can detoxify them rapidly, considering the relatively simple hydrocarbon structures of the monoterpenoids. 

From a toxicological point of view, mercury is not an entity. The toxic effects of mercury compounds are very much dependent on in which the type of molecule the mercury is presented to the tissue. Although the history of mercury toxicology goes back to the Chinese, 754 BC (Almkvist, 1903), this has not become evident until the last 30 years. As the topic of this conference is mercury exposure via food to the infant,... 

Lead has long been known to produce toxic effects on the heart and blood vessels in human populations and to show links to cardiovascular morbidity and mortality. A number of pubhc agency expert consensus documents have discussed the topic, including lARC (2006), NAS/NRC (1993), U.S. EPA (1977, 1986, 2006), U.S. ATSDR (2007), and WHO (1995). In addition, individual critical reviews have appeared (Navas-Acien et al., 2008, 2007 Vaziri, 2008). This chapter presents some of the more salient toxicological, epidemiological, and mechanistic aspects of these effects and a contexmal comparison with other key toxic endpoints of lead exposure. 

The previous parts of this monograph have already provided some quantitative looks at lead and public health within more specific topics. Part 1 presented a measure of the entirety of lead contamination in the human environment, while Part 2 offered descriptions of the nature and extent of lead exposures in the United States and internationally. Part 3, in providing the range of Pb toxic effects in human populations, also referred to various expressions of Pb exposures reported as linked to these various effects epide-miologically. The need to translate those earlier parts and chapters into a coherent expression of threat of harm to human health remains. 

Stratification of lead s toxicity in humans into diagnosable disease or probabilistic risks of disease is not simply defined by where exposures and toxic effects align across the full spectrum of lead s dose—response relationships. That is, one cannot infer that only historic clinical effects at high Pb exposures comprise diagnosable disease and that subclinical effects always require population or epidemiological approaches. See the historical scientific perspective on these topics by Mushak (1992). 

As noted in Section 2.1, the relationship between the chemical nature of substances and their toxic effects is addressed by the topic of toxicological chemistry (Figure 2.13). In addition to their chemical properties, toxicological chemistry addresses the sources and uses of toxic substances and the chemical aspects of their exposure, fate, and disposal. The theory of toxicological chemistry is treated by the science of quantitative structure-activity relationships (QSAR), which relates the chemical nature of substances to their reactions in biological systems. ... 

It should be understood that the types of toxic effects discussed above are limited to situations where nanoparticles ctfe inhcded or placed in the trachea as insoluble particles. The form of nanoparticles in applications are either dissolved in solution (e.g., through injection for medical uses) or inside components (e.g., computers) and are likely not available for exposure in these ways. We expect that the risk of toxic effects is significantly reduced in these types of products. However, incidental inhalation exposure by workers in the industry represents a potential health issue that requires more research. This is well understood by the U.S. National Institute of Occupational Safety and Health (NIOSH). They recommend limiting exposure to workers until more knowledge is gained, and have identified ten key research topics, including ... 

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