Species-Specific Chronic Toxicity

The observation that imposex occurred primarily in marinas suggested causality with some contaminant originating from such facilities. Field experiments demonstrated that neogastropods transferred from pristine sites to marinas often developed imposex. Laboratory studies eventually implicated tributyltin, a biocide used in marine paints, as the cause of imposex. Tributyltin is toxic to most marine species evaluated in the 

Species Acute Toxicity (LC50, qg/L) Chronic Toxicity (LOEL, qg/L) Imposex (qg/L) 

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Subacute and chronic toxicity of alcohol and alcohol ether sulfates has been extensively tested in several animals and sometimes humans. The duration of the tests was in some cases as long as 2 years. When administered below the toxic amount no specific damages were observed in any of the species tested [333]. No severe side effects were observed in the study by Swisher, carried out with volunteers who ingested considerable amounts of anionic and nonionic surfactants over long periods [348]. Similarly, the effects produced by the intake of daily doses of 1 g of alcohol sulfate per person over 8 weeks [349],... 

Chronic toxicity Lack of models because of species-determined biological specificity and antigenicity Models sometimes relevant... 

While rDNA techniques offer exciting possibilities, there are many unanswered questions about the potential toxicity that each new product represents. For example, acute clinical toxicities of interferons (IFNs) include flu-like syndrome, fever, chills, malaise, anorexia, fatigue, and headache. Chronic dose-limiting toxicities include neutropenia, thrombocytopenia, impairment of myeloid maturation, reversible dose-related hepatotoxicity, some neurological toxicity (stupor, psychosis, peripheral neuropathy) and gastrointestinal toxicity. Some of these toxicities would be difficult to ascertain in rodents, and, in fact, may be species-specific. 

Table 7 Example application of process in Box B to evaluate the risk of dioxins in Dutch sediments. No observed effect (NOEC) concentrations for chronic toxicity of dioxins in vertebrates (immune, reproductive and developmental toxicity) expressed as internal concentration (ng TEQ/g Iw). The sediment to fish bioconcentration factor is set at 4 (ng TEQ/g Organic Carbon to ng/g lipid weight in fish) based on Traas et al. (2001). Based on a species-specific biomagnification factor (BMP) from fish to animal (ng TEQ/g Iw) the internal NOEC is extrapolated to a NOEC in sediment. These data are used to construct the SSDs in Figures 5 and 6.

Reproductive toxicity studies with PS ODNs have been performed with both human-specific sequences as well as species-specific sequences. Like chronic studies, this combination of human drug and surrogate provides insight into whether any effects observed are class related or target related. 

ISO 10993 testing is intended to evaluate materials such as metals and polymers that essentially do not interact directly with the human immune system. However, the presence of an antibody on the device surface introduces the potential for cross-species reactions that may not be indicative of performance in humans. These interactions may affect some or all ISO 10993 in vivo tests. For example, the duration of chronic toxicity testing may be limited based on induction of immune responses or carcinogenicity studies may not be appropriate based on the specific product attributes of the antibody. 

Sensitivity is a criterion that is used in the choice of a test species. The sensitivity of the species in Table 3 relative to one another as well as to indigenous flora and fauna in the ecosystem is a matter of contention. There is no single test species and no group of test species consistently most sensitive to toxicants or most reliable for extrapolation to all other organisms. Most toxic effects reported for a variety of test substances have been species-specific. Therefore, acute toxicity tests are conducted first with a variety of freshwater and marine test species to determine the most sensitive plant and animal. These sensitive species then are used in all subsequent chronic testing. 

No studies were located that specifically examined species-related differences in selenium pharmacokinetics. Similar patterns of absorption, distribution, and elimination have been reported for human and animal systems and the dermal, endocrine, and neurological effects of chronic exposure in humans are similar to those reported for animals exposed to very high doses of selenium. However, species-specific differences in toxicity are present (e.g., the main effect of selenium toxicity in rodents is damage to the liver, which is not observed in humans) and this may represent evidence of underlying differences in how selenium is metabolized. 

The toxic effects of the mineral elements are extremely element- and species-specific (Hapke 1991). The symptoms of acute poisoning (Geldmacher von Mallinckrodt 1991a) and chronic toxicity of inorganic elements can be completely different (Ewers and Schlipkoter 1991). The most common symptoms of acute metal poisoning include the following ... 

Chronic Toxicity. Various animal species have imdergone repeated oral exposure to phthalates for periods up to two years. Tumors were foimd in rodents at a dose level higher than what humans are exposed to. In mechanistic studies these tumors were found to be specific to rodents and therefore the effect is not relevant for humans. At lower dose levels, still many times higher than what humans are exposed to, no tumors are present. In these mechanistic studies phthalates were not genotoxic. Both in vivo and in vitro studies did not indicate... 

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