Chemicals acute effects

After the use of a chemical becomes widespread, new deleterious effects on human health may be observed. In such situations, the occupational limit values will have to be modified. Usually the OELS tend to decrease when more information on the toxicity of a chemical is obtained. Knowledge of the specific features of various chemicals is thus extremely important for planning ventilation of industrial premises. It is important to be especially aware of those chemicals that may cause long-term effects without causing any acute effects. There are also compounds such as isocyanates that are extremely irritating at concentrations as low as 0.5 ppm. However, some workers may become sensitized to isothiocyanates at a concentration of 10 ppb, and therefore this has to be taken into consideration when planning the industrial ventilation. Thus, one has to plan against compounds that can cause serious health effects at concentrations at which their presence cannot be observed by the human senses, i.e., irritation or odor. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

The data in animals are insufficient to derive an acute inhalation MRL because serious effects were observed at the lowest dose tested (Hoechst 1983a). No acute oral MRL was derived for the same reason. The available toxicokinetic data are not adequate to predict the behavior of endosulfan across routes of exposure. However, the limited toxicity information available does indicate that similar effects are observed (i.e., death, neurotoxicity) in both animals and humans across all routes of exposure, but the concentrations that cause these effects may not be predictable for all routes. Most of the acute effects of endosulfan have been well characterized following exposure via the inhalation, oral, and dermal routes in experimental animals, and additional information on the acute effects of endosulfan does not appear necessary. However, further well conducted developmental studies may clarify whether this chemical causes adverse developmental effects. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. 

Specific short-term exposure limits are listed by the HSE for those chemicals which pose a risk of acute effects from brief exposures. For other chemicals a recommended guideline for controlling short-term excursions is to restrict them to 3x long-term exposure limit averaged over a 10min period. 

The increase in environmental awareness and the acute effects of some toxic compounds have raised questions over the safety of using many chemicals invented for agricultural and industrial applications. A great deal of current research addresses the management and remediation of old contaminated sites. Recent concerns regard the safety of consumer chemicals, especially nanomaterials the effect of pharmaceuticals on ecosystems and the combined effect that chemical cocktails have on human and ecosystem health. 

Roudabush RL, Terhaar CJ, Fassett DW, et al. 1965. Comparative acute effects of some chemicals on the skin of rabbits and guinea pigs. Toxicol Appl Pharmacol 7 559-565. 

Certain (ACGIH) criteria may be appropriate for use as benchmarks. The ACGIH threshold limit values — TLV-STELs and TLV-Cs — are designed to protect workers from acute effects resulting from exposure to chemicals such effects include irritation and narcosis. These criteria are discussed in chapter 2. These criteria can be used for toxic gas dispersion but typically produce a conservative result because they are designed for worker exposures. 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

For highly potent APIs, profound effects can occur at low ng levels, the adverse effect of ethynylestradiol on fish populations is one example [107]. Another example is the development of resistant bacterial strains induced by the release of antibiotics into the environment [112, 113]. Dome et al. [114] concluded that fluoxetine, ibuprofen, diclofenac, propranolol and metoprolol exhibit relatively high acute toxicity to aquatic species. In addition, due to the inherent properties of these chemicals, pharmacodynamic effects were observed in the heart rate of Daphnia magna for the (3-blockers propranolol and metoprolol. 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular effects in humans. Acute-duration dermal exposure caused skin necrosis in rabbits however, effects were reversible within 2 weeks (Duprat and Gradiski 1978). Nasal irritation resulted from 15 minute exposure to vapor concentrations of 155 ppm (de Ceaurriz et al. 1988). No dermal/ocular effects were seen following intermediate- or chronic-duration dermal exposure in rabbits. Based on acute effects in rabbits, hexachlorobutadiene may pose some risk to humans following skin contact with the chemical-depending on the area exposed. Inhalation of vapors may cause irritation of the nasal mucosa. 

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