Humans, toxicity/potential risk

Hertwich EG, Mateles SF, Pease WS, McKone TE (2001) Human toxicity potentials for life cycle assessment and toxics release inventory risk screening. Environ Toxicol Chem 20 928-939... 

Tables 2.6 and 2.7 give examples of the modes of action of pollutants in animals and in plants/fungi, respectively. It is noteworthy that many of the chemicals represented are pesticides. Pesticides are designed to be toxic to target species. On the other hand, manufacturers seek to minimize toxicity to humans, beneficial organisms and, more generally, nontarget species. Selective toxicity is an important issue. Regardful of the potential risks associated with the release of bioactive compounds into the environment, regulatory authorities usually require evidence of the mode of toxic action before pesticides can be marketed. Other industrial chemicals are not subject to such strict regulatory requirements, and their mode of action is frequently unknown.

McKone TE, Layton DW (1986) Screening the potential risks of toxic substances using a multimedia compartment model estimation of human exposure. Regul Toxicol Pharm 6 359-380... 

The evaluation of risk has underlined the possible adverse effects both on human health after the exposure to drinking water contaminated by landfill leachate and on small rodents and aquatic species at the hypothesized condition for humans, the estimated toxic effects of the raw leachate are mainly due to the levels of ammonia and cadmium and carcinogenic effects are induced by arsenic first and then by PCBs and PCDD/Fs while ecological potential risk is mainly attributable to the concentration of inorganic compounds, in particular ammonia for small rodents, cadmium, ammonia, and heavy metals for fishes. 

The Stockholm Convention on POPs lists 22 priority chemical substances that pose potential risks of causing adverse effects to human health and the environment. Since the convention was enacted in 2004, evidence for the toxic effects of POPs such as DDT, dichlorodiphenyldichloroethylene (DDE), PCBs, PCDD/Fs and other halogenated compounds has been demonstrated for both humans and wildlife. 

For most chemicals, actual human toxicity data are not available or critical information on exposure is lacking, so toxicity data from studies conducted in laboratory animals are extrapolated to estimate the potential toxicity in humans. Such extrapolation requires experienced scientific judgment. The toxicity data from animal species most representative of humans in terms of pharmacodynamic and pharmacokinetic properties are used for determining AEGLs. If data are not available on the species that best represents humans, the data from the most sensitive animal species are used to set AEGLs. Uncertainty factors are commonly used when animal data are used to estimate minimal risk levels for humans. The magnitude of uncertainty factors depends on the quality of the animal data used to determine the no-observed-adverse-effect level (NOAEL) and the mode of action of the substance in question. When available, pharmocokinetic data on tissue doses are considered for interspecies extrapolation. 

The Office of Toxic Substances has assembled a team of multi-disciplined scientists to review each of these PMNs and assess the potential risks to human health and the environment posed by commercial manufacture and sale. These assessments are based upon limited firm data on the specific chemical, comparison with structurally similar chemicals of known toxicity, plus estimates of exposure from calculations of the potential number of people involved in manufacturing and processing operations and in consumer use. Most PMNs contain elementary data on physical and chemical properties and obvious acute health effect such as skin... 

In short, CNTs own potential nanohazards because we still do not know the concrete metabolism course of CNTs within cells and human body, and possible effects on heredity, gene transcriptional, and post-translational regulations, at present, we still do not have enough proofs to confirm CNTs are no toxic, thereby the key is to find these methods to reduce potential risk of CNTs by series of studies. 

CNTs are of importance as useful bio-nanomaterials for pharmaceutical applications and biomedical engineering. However, despite the contribution of CNTs to bio-nanomaterials for pharmaceutical applications, the potential risks of CNTs about the exposure to human health have not been adequately assessed. Toxicology issues associated with CNT inhalation, dermal toxicity, pulmonary, biodistribution, biocompatibility, blood compatibility, and elimination need to be addressed prior to their pharmacological application in humans. 

Liver toxicity related to 1,2-dibromoethane depends on the metabolic pathway utilized and the amount of damage induced in cellular protein and membrane structures. Humans exposed to low levels of 1,2-dibromoethane are at potential risk of having toxic events occurring within hepatocytes whether these effects will be subcellular or result in cell necrosis may depend on internal dose and a variety of factors. Liver damage that is severe enough to cause clinical disease in humans from low-level exposure is unlikely. 

Other preharvest techniques include the development of more resistant crops (e.g., Becker, 1999 Guo et al., 1998), and biological control with atoxigenic A. flavus strains (Cotty, 1990 Dorner et al., 1998). Atoxigenic A. jiavus competed successfully with a toxic isolate when they were grown in mixed culture, obtaining a reduction of the aflatoxin content by 82 to 100%. This is a worthwhile approach for control, however possible side effects caused by a preemptive application of A. jiavus in the environment must be studied to determine potential risks to human and animal health. 

Reproductive Toxicity. No studies were located regarding the reproductive effects of thorium in humans following exposure by any route. Neither inhalation nor oral reproduction studies in animals were located. Pharmacokinetic data following inhalation or oral exposure were not located to allow the prediction of possible reproductive effects. One dermal rat study found testicular effects after administration directly onto the scrotal skin. Additional inhalation, oral, and dermal reproduction studies and multigenerational studies would be helpful in assessing the potential risk to humans. 

Chemical-induced reproductive toxicity consists of effects on reproductive performance (e.g., fertility and fecundity), the reproductive tract, and/or sexual development. Reproductive toxicity has been routinely assessed, using laboratory animal studies, in the chemical risk assessment process for over 40 years. For environmental chemicals, the multigeneration reproduction and fertility study in rats has been the primary tool for assessing reproductive toxicity potential in humans. Unfortunately, these expensive and animal-intensive studies have only been conducted on a fraction of environmentally... 

In summary, in studies of chemical toxicity, pathways and rates of metabolism as well as effects resulting from toxicokinetic factors and receptor affinities are critical in the choice of the animal species and experimental design. Therefore it is important that the animal species chosen as a model for humans in safety evaluations metabolize the test chemical by the same routes as humans and, furthermore, that quantitative differences are considered in the interpretation of animal toxicity data. Risk assessment methods involving the extrapolation of toxic or carcinogenic potential of a chemical from one species to another must consider the metabolic and toxicokinetic characteristics of both species. 

Data from biomonitoring studies are becoming widely available and are increasingly used to understand the presence of chemicals in the human body and their effects on human health. At the same time, scientists, public-health officials, and the public have questions about the quality and scope of the available data, what the data tell us about potential risks to human health, and how future research can address these questions. Responding to a congressional request, the National Research Council established the Committee on Human Biomonitoring for Environmental Toxicants to review current practices in and recommend ways to improve the interpretation and uses of human biomonitoring for environmental toxicants. 

Chronic-Duration Exposure and Cancer. Limited studies are available on the effects in humans chronically exposed to chlorobenzene via inhalation and suggest that nervous system is a target tissue. Specific exposure data were not provided. No information is available on effects of chlorobenzene in humans following chronic oral or dermal exposure. Inhalation and oral studies in animals identified the same target tissues as for intermediate-duration exposure. One study in rats demonstrated that the immune system can also be adversely affected via oral exposure. Inhalation studies in humans and inhalation and oral studies in animals are sufficient to identify main target tissues. A chronic MRL was not derived since human exposure data were lacking and the one animal study did not evaluate a sufficient number of end points and test animals. Further studies via the dermal route would provide additional toxicity data for an assessment of potential risk to humans. 

Of the various ways of designating a solid waste as hazardous described above, only the toxicity characteristic is based on a quantitative assessment of potential risks resulting from waste disposal. The specifications of ignitable, corrosive, and reactive waste are based on qualitative considerations of risk, in that the presence of materials with these characteristics in a disposal facility clearly constitutes a hazard that could compromise the ability of the facility to protect public health. The specifications of listed hazardous wastes are based on risk in the sense that the listed substances have been identified as potentially hazardous to human health. However, requirements for treatment and disposal of listed waste discussed in Section 4.2.2 do not distinguish between different wastes based on considerations of risk from disposal. 

---