Chronic study

For the above reasons, chronic exposure studies are frequently designed in such a way that it is possible to combine observations for tumorigenesis and noimeoplastic tissue injury. Chronic studies are usually extensively monitored. It is common practice to sacrifice animals at intervals during the study in order to detect the onset of any tissue injury. For two-year exposure studies, it is most meaningful to have interim sacrifices at 12 and 18 months. 

Chronic studies Rats/inicc 1 8--14 months Chronic effects of low exposures... 

A UF of 10 is used when a NOAEL derived from a subchronic instead of a chronic study is used as the basis for a chronic RfD. 

Osbome-Mendel rats appeared to be the most sensitive to the renal effeets of trichloroethylene. At a dose of 500 mg/kg/day, toxic nephrosis occurred in 78% of male and 60% of female Osbome-Mendel rats, 37% of male and 45% female ACI rats, 36% of male and 63% of female Marshall rats, and 20% of male and 17% female August rats. Another chronic study revealed renal tubular nucleocytosis in 50% of male rats exposed to 250 mg/kg/day trichloroethylene for 52 weeks by oil gavage (Maltoni et al. 1986). Further explanation of these studies is in Section 2.2.2.8. 

Studies in animals indicate that the effects of lead on heme synthesis occur in many tissues and that the time courses of these effects depends on the tissue, exposure duration, and the chemical and animal species administered. Oral exposure of rats to lead acetate increased liver ALAS activity in a single dose study (Chmielnicka et al. 1994), decreased liver ALAS activity in a chronic study (Silbergeld et al. 

Reith M., Fischette C. Sertraline and cocaine-inducted locomotion in mice. II. Chronic studies. Psychopharmacology. 103 306, 1991. 

In a chronic study in rats (Quast et al. 1980a), some changes in the blood parameters measured were observed at various intervals during the study, but the findings did not occur consistently and were not dose-related. Therefore, the authors concluded that these findings were not direct effects of exposure to acrylonitrile, but rather were a secondary response to other effects such as weight loss, tumor formation, or inflammatory reactions. 

Chronic studies in rats indicate that lifetime exposure to doses of 4.4 mg acrylonitrile/kg body weight/day (mg/kg/day) or higher may result in premature death (Bio/dynamics 1980a, 1980b,... 

A consistent observation in rats exposed to acrylonitrile was increased liver weight, both in acute studies at 65 mg/kg/day (Murray et al. 1978) and chronic studies at 10 mg/kg/day (Bio/dynamics 1980a, 1980b, 1980c). Again, this may be an adaptive change related to increased metabolic activity by the liver due to the presence of acrylonitrile in the body. 

In humans, severe cases of acrylonitrile poisoning have resulted in low grade anemia (Wilson 1944 Wilson et al. 1948), but complete recovery was reported. Chronic occupational exposure to low levels of acrylonitrile has not resulted in detectable effects on the hematological system (Sakurai et al. 1978). In intermediate and chronic studies in animals, decreased red cell count, hemoglobin concentration and hematocyte were observed (Bio/dynamics 1980a, 1980b, 1980c Quast et al. 

Immunotoxicity. No information was found on the immunological effects of acrylonitrile in humans or animals by any route of exposure. Because no Immunopathological effects have been reported in subchronic and chronic studies involving multiple species, additional studies employing a more specific testing battery are not warranted at this time. 

Lijinsky, W. 1988. Chronic studies in rodents of vinyl acetate and compounds related to acrolein. Ann. NY Acad. Sci. 534 246-254. 

Prenatal and postnatal exposures to fenvalerate reduced prostate and seminal vesicle weights and plasma testosterone levels in male rats [55], A chronic study showed no adverse effects on reproductive tissues at a high dose level of 1,000 ppm [142]. In vivo and in vitro studies with rats and mice suggested that fenvalerate may affect male and female reproduction, possibly due to calcium transport alteration [143-146], One paper reported that fenvalerate affected human sperm count and sperm motility of male workers who were exposed to fenvalerate in a pesticide factory [147]. 

Acute toxicity should be determined in three species subacute or chronic studies should be by the route to be used clinically. Suitable mutagenicity studies should also be... 

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