Animals chronic effects

Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

Some values for tests on rats are given in Table 9.1. Estimates of the LD50 for man are based on tests on animals. The LD50 measures the acute effects it gives only a crude indication of the possible chronic effects. 

Intake can be expressed either as a pollutant mass per unit time, as discussed above, or as a mass per kg of body weight per unit time. The latter expression facilitates comparison to health effects data, especially laboratory animal data, which are commonly reported in equivalent units. Similarly, depending on the route of exposure, intake may be estimated on an annual basis to address chronic effects, or on a smaller time scale for addressing acute effects including lethality, teratogenesis, reproductive and neurotoxic effects. 

Chronic exposure to GD causes forgetfulness, thinking difficulty, vision disturbances, muscular aches/pains. Although certain organophosphate pesticides have been shown to be teratogenic in animals, these effects have not been documented in carefully controlled toxicological evaluations for GD. 

In this paper I have tried to show that measurement of health benefits attributable to TSCA is not feasible. I hope that in doing so I have not belabored the obvious. For new chemicals and for most existing chemicals, prospective evaluation of health benefits to be achieved by various exposure controls will have to be based on extrapolation from microbial and animal data. However, while such extrapolation may be useful in a qualitative sense, quantitative risk assessment techniques involve considerable uncertainty, and in any case have not been developed for chronic effects other than cancer. 

One of the prime concerns, apart from acute and subacute toxicity, is the question of whether a product causes chronic effects. In this context, carcinogenicity studies are of cardinal importance. A possible chronic hazard may be indicated by epi-demological studies. Where such investigations are not available, experiments are performed on animals for the duration of their entire life span. The type of application depends on the exposition (perorally, dermally, per inhalation). 

Federal agencies such as the FDA and EPA require a battery of toxicity tests in laboratory animals to determine an additive s or a pesticide s potential for causing adverse health effects, such as cancer, birth defects, and adverse effects on the nervous system or other organs. Tests are conducted for both short-term (acute) and long-term (chronic) toxicity. For chronic effects other than cancer, laboratory animals are exposed to different doses to determine the level at which no adverse effects occur. This level is divided by an uncertainty or safety factor (usually 100) to account for the uncertainty of extrapolating from laboratory animals to humans and for individual human differences in... 

A full set of studies normally includes short-term and long-term animal studies on chronic effects and potential carcinogenicity, studies on reproductive and developmental toxicity, genotoxicity, kinetics and metabolism, pharmacological properties and special studies depending on the characteristics of the substance and observation in the standard set of studies. Human clinical studies may be necessary for substances which are metabolised and may interfere with functions of the human body. 

In studies of the fate of hydrocarbons in terrestrial animals, considerable attention is directed toward relations between aromatic hydrocarbon metabolism, interactions of metabolites with macromolecules (e.g., DNA), and the formation of neoplastic lesions (] ). A broad perspective exists in studies with marine organisms. In the aquatic forms, exposure to pollutants that are rich in aromatic hydrocarbons, such as petroleum, leads to a wide variety of acute and chronic effects (2J. Attempts to delineate these effects require an understanding of the accumulation of the xenobiotics in tissues and an assessment of metabolite formation and retention. The important additional problem of the interaction of metabolites with genetic materials has not been studied to an appreciable degree in marine life. 

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. 

Aqueous and sedimentary TBT and TFT cause chronic and acute effects in algae, zooplankton, Crustacea, mollusks, fish, and animals. These effects have been local in nature, occurring mostly in harbors near industrialized lands. TBT is bioaccumulated in many species, which is unfortunate as it is a potent endocrine disrupter. The enrichment factor in mussels, snails, and oysters ranges from 10,000 to 60,000. As mentioned in Section 28.7.1, TBT induces imposex in marine gastropods. 

Immunotoxicity. No information on immunotoxicity after exposure to 1,3,5-TNB by any of the three routes is available in humans or animals. Therefore, animal studies following acute, intermediate, and chronic exposure to 1,3,5-TNB via all three routes would help in estimating the potential immunotoxic effects in humans. Spleen enlargement was reported in acute-(Blackburn et al. 1988) and intermediate-duration (Cody et al. 1981 Linder et al. 1986) studies in animals. These effects, however, were secondary to adverse hematological effects. Studies in laboratory animals following acute exposure to 1,3-DNB by the oral route would help define possible effects on antibody production and cellular immunity. This information could be used to determine populations sensitive to possible exposure to 1,3-DNB at locations close to ammunition plants or in specific workplaces. 

Toxicology. 2,6-Di-tert-butyl-p-cresol or BHT is of relatively low acute toxicity in animals, and there is no evidence of either acute or chronic effects among exposed workers. 

Toxicology. 1,2-Epoxybutane exposure causes body weight effects and nasal lesions in experimental animals chronic exposure is carcinogenic to rats but not to mice. 

In inhalation studies conducted by the National Toxicology Program, acute, subchronic, and chronic effects of ethyl bromide were examined in mice and rats. All mice and three of five female rats died before the end of a 4-hour exposure to 5000 ppm rats and mice exposed to 2 000 ppm 6 hours/day died before the end of 14-day studies. In 14-week studies, 1600 ppm was lethal to some animals and caused compound-related lesions including muscle atrophy and atrophy of the testis and uterus thought to be secondary to body weight loss rats also had minimal to moderate multifocal mineralization in the cerebellum and minimal-to-severe hemosiderosis of the spleen. 

No acute or chronic effects have been reported from human exposure. Limited animal data suggest that the respiratory system is the target of inhalation exposure. The urinary bladder is considered the target organ after oral administration. 

On the basis of acute animal studies, n-propyl alcohol appears to be slightly more toxic than isopropyl alcohol. No chronic effects have been reported in humans, although a human fatality has been ascribed to ingestion. Exposure to 400 ppm for 3-5 minutes will reportedly... 

Chronic-Duration Exposure and Cancer. No studies of chronic duration were found in humans or animals. Chronic toxicity information is important because people living near hazardous waste sites might be exposed to cresols for many years. Prolonged exposure to cresols in humans might occur by oral, inhalation, or dermal routes. Chronic studies would enable discovery of effects produced by long-term exposure to relatively low levels of cresols, which might not be detected in shorter-term studies. 

The exposure distribution and species sensitivity distributions were integrated to generate risk curves for chronic effects. From the 504 000 values in the exposure exceedence curve, annual maximum concentrations corresponding to each 0.5th percentile were determined. The percentage of plant or animal species whose chronic NOEC would be exceeded at each of these concentrations was calculated from the log-normal SSD model. The percentage of plant or animal species affected at each exposure exceedence percentile was plotted as shown in Figure 4.5. 

The types of scientific tests needed to estabhsh safety are dependent on the nature of the regulated product and its proposed use. A product such as a food or color additive will require tests to elucidate the potential of the product to induce adverse acute, subchronic, and chronic effects. The safety tests are generally performed in animals and other biological systems. Both the t5rpes of tests and the methodology of particular tests have changed over the years with scientific advances in the field of toxicology. 

The Committee analyzed published studies describing the In vivo and in vitro properties of the agents used and reviewed short-term data collected by the U.S. Army on volunteers. The ability to provide definitive answers to the questions raised by the charge to the Committee was limited by the absence of long-term followup studies of the soldiers and by the sparseness of chronic effects studies of these compounds In animals or In humans after industrial exposure. 

Reasonably good testing methods exist for acute toxicity. The tests use surrogate animals, and the correlation to humans is the weakest element. The quality of predictive modehng for acute effects based on SAR (Structure Activity Relationships), is only modest. For chronic effects, testing with surrogates for humans is modestly good, particularly for cancer. Tests for chronic toxicity in animals are only fair and for... 

---