Toxic exposure chronic

Cory-Slechta DA, Thompson T. 1979. Behavioral toxicity of chronic postweaning lead exposure in the rat. Toxicol Appl Pharmacol 47 151-159. 

Foster WG. 1992. Reproductive toxicity of chronic lead exposure in the female Cynomolgus monkey. Rep Toxicol 6 123-131. 

Data for PCP and terrestrial wildlife are incomplete and — in view of the large interspecies variations in sensitivity — need to be collected. Research is needed on reproductive effects in animals following inhalation exposure to PCP additional acute and intermediate toxicity testing chronic duration exposure studies on cancer induction, genotoxicity, and immunotoxicity and the development of alternate biomarkers of PCP exposure and antidotes (WHO 1987 USPHS 1994). Until the results of these studies become available, it seems reasonable to apply to wildlife the same levels recommended for human health protection. 

Chronic Toxicity To assess the toxicity following chronic (lifetime) exposure hy the route of intended exposure... 

Ratanasavahn, D., Baffet, G., Latinier, M.R, Fissel, M. and Guillouzo, A. (1988). Use of hepatocyte co-cultures in the assessment of drug toxicity from chronic exposure. Xenobio-tica 18 765-771. 

Chronic-Duration Exposure and Cancer. No information is available regarding the toxicity of chronic-duration exposure of humans to mirex by the inhalation or dermal route of administration. Animal studies have not been located for chronic mirex administration by the inhalation or dermal routes however, oral studies exist (Chu et al. 1981a Gaines and Kimbrough 1970 NTP 1990 ... 

An occasional common side effect of capsaicin exposure is bronchoconstriction, in asthmatic people, caused by inhaled airborne particles. In nonasthmatic people, this induces a cough. This is prevented by washing the skin surface where capsaicin was applied after 30-40 minutes of exposure. Chronic overdosage can cause chronic gastritis, kidney and liver toxicity, and neurotoxic effects. 

Humans are susceptible to the acute toxic effects of 1,2-dibromoethane from various routes of exposure. Except for adverse reproductive effects in men after occupational exposure, chronic effects of 1,2-dibromoethane exposure have not been documented in humans. Based on data derived from animal studies, mechanisms of action of 1,2-dibromoethane at a cellular level, toxicokinetics, and genotoxicity tests, there is a potential for certain adverse health effects in humans exposed chronically to low environmental levels of 1,2-dibromoethane that could exist near hazardous waste sites or areas of former agricultural use. 

The toxicity of chronic exposure to arsenic is well established and the best recommendation is to avoid arsenic exposure. The most common home exposure is from contaminated drinking water and arsenic-treated lumber. Certain areas of the country have higher levels of arsenic in water. The EPA has lowered arsenic drinking water standards, but water providers have until 2006 to meet the new standards. Avoid inhalation of sawdust from arsenic-treated lumber or inhalation of smoke from burning arsenic-treated wood. And of course always wash your hands. This is particularly important if a young child is playing on arsenic-treated wood. 

Nitric oxide gas is moderately toxic. Exposure can cause severe irritation of the eyes, nose, and throat. Chronic inhalation produces pulmonary edema, irritation of the respiratory tract and corrosion of teeth. 

The ERA has calculated a subchronic oral reference dose (RfD) of 7x10 mg/kg/day for carblon tetrachloride based on a NOAEL of 1 mg/kg/day (converted to 0.71 mg/kg/day based on intermittent exposure) for rats in a 12-week study (Bruckner et al. 1986 ERA 1989b IRIS 1993). The critical effect was liver toxicity. A chronic oral RfD of 7x10 mg/kg/day was also calculated based on the same NOAEL used for the subchronic RfD. The ATSDR has calculated an acute inhalation MRL of 0.2 ppm based on a LOAEL of 50 ppm for liver effects in an acute 4-day rat inhalation study (David et al. 1981), and an intermediate inhalation MRL of 0.05 ppm based on a NOAEL of 5 ppm for liver effects in an intermediate-duration (187-192 days) inhalation study in rats (Adams et al. 1952). The ATSDR has also calculated an acute oral MRL of 0.02 mg/kg/day based on a LOAEL of 5 mg/kg/day over 10 days for liver effects in the rat (Smialowicz et al. 1991), and an intermediate oral MRL of 0.007 mg/kg/day based on a NOAEL of 1 mg/kg/day over 12 weeks (converted to 0.71 mg/kg/day based on intermittent exposure) for liver effects in the rat (Bruckner et al. 1986). 

Thus, the frequency of exposure is also an important factor because the concentration to which the organism, and more particularly the target site, is exposed can remain relatively constant or increase. As illustrated above, this is because repeated exposure may lead to accumulation of the chemical, depending on its half-life (see chap. 3), such that intake exceeds elimination. Thus the chemical can accumulate in the organism because of saturation of metabolism or elimination or because its physicochemical properties determine that the chemical becomes sequestered in tissues such as fat. Another factor in toxicity from chronic exposure can be the ability to repair damage or replace macro molecules and the speed with which this is done. If damage is not repaired or macro molecules are not replaced before the next exposure, then accumulation of damage or effect can also occur. 

TOXICITY. The ability of a substance to cause damage to living tissue, impairment of the central nervous system, severe illness, or, in extreme cases, death when ingested, inhaled, or absorbed by the skin. The amounts required to produce these results vary widely with the nature of the substance and time of exposure to it, Acute toxicity refers to exposure of short duration, i.e.. a single brief exposure chronic toxicity refers to exposure of long duration, i.e., repeated or prolonged exposures,... 

Figure 11.1 Examples of exposure/effect scenarios that result in either acute toxicity (a), chronic toxicity (/ ). or mixed acute/chronic toxicity (c,d). Examples for each scenario are provided in the text.

Golub MS, Gershwin ME, Donald JM, et al. 1987. Maternal and developmental toxicity of chronic aluminum exposure in mice. Fundam Appl Toxicol 8 346-357. 

Distinguish among acute local exposure, chronic local exposure, acute systemic exposure, and chronic systemic exposure to toxicants. 

Toxicity The degree to which a substance or mixture of substances can harm humans or animals. Acute toxicity involves harmful effects in an organism through single or short-term exposure. Chronic toxicity is the ability of a substance or mixture of substances to cause harmful effects over an extended period, usually on repeated or continuous exposure, sometimes lasting for the entire life of the organism. Subchronic toxicity is the ability of the substance to cause effects for more than 1 year but less than the lifetime of the organism. 

Lack of relevant species compromises toxicity testing (e.g., limit to 1 species, unable to evaluate reproductive toxicity). Exposure-limiting immunogenicity compromises chronic studies... 

The most important factor is the dose-time relationship. The amount of a substance that enters or contacts a person is called a dose. An important consideration in evaluating a dose is body weight. Dose is the quantity of a chemical substance that a surface, plant, or animal is exposed to. Time means how often one is exposed to or the duration of exposure to a chemical substance. In simple terms, the dose-time relationship provides information on how much of the test substance is involved and how often the exposure to the test substance occurs. This relationship gives rise to two different types of toxicity of a chemical substance—namely, acute toxicity and chronic toxicity. 

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