Animal studies acute toxicity

Chronic-Duration Exposure and Cancer. No studies were located following chronic-duration exposure to either 1,3-DNB or 1,3,5-TNB in humans or animals. This may be because both compounds were shown to be potent acute toxicants. Animal studies that examine the effects of 1,3-DNB and... 

CN AND CS Toxicity in Animals In animal studies, the cause of death from CN inhalation is the result of toxicity in the pulmonary system. Post-mortem examination from acute toxicity lethality studies in animals... 

Hydraziae is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydraziae irritates the skin, eyes, and respiratory tract. Liquid splashed iato the eyes may cause permanent damage to the cornea. At high doses it can cause convulsions, but even low doses may result ia ceatral aervous system depressioa. Death from acute exposure results from coavulsioas, respiratory arrest, and cardiovascular coUapse. Repeated exposure may affect the lungs, Hver, and kidneys. Of the hydraziae derivatives studied, 1,1-dimethylhydrazine (UDMH) appears to be the least hepatotoxic monomethyl-hydrazine (MMH) seems to be more toxic to the kidneys. Evidence is limited as to the effect of hydraziae oa reproductioa and/or development however, animal studies demonstrate that only doses that produce toxicity ia pregaant rats result ia embryotoxicity (164). 

Human and animal studies indicate that inorganic manganese compounds have a very low acute toxicity by any route of exposure. The toxicity values for a given Mn compound are shown in Table 20 to depend on the species of test animal as well as the route of exposure. Manganese concentrations as high as 2000 ppm were found to be tolerated by test animals over a six-month period without any ill effects (208). 

Toxicity. The acute toxicity of chlotinated paraffins has been tested ia a range of animals and was found to be very low (4). A comprehensive study (5) demonstrated that the toxicity of chlotinated paraffins was related to carbon chain length and to a lesser degree chlorine content. The shorter chain-length chlotinated paraffins were more toxic than the longer chain chlotinated paraffins. 

Carcinogenicity of DGEBPA or DGEBPA-based resins, as measured by topical appHcation, has not been shown by a majority of the studies (45). Advanced DGEBPA resins exhibit low systemic toxicity either by dermal or oral routes and inhalation of these resins is unlikely because of low volatihty. The acute oral LD q in rats has been reported to be >2000 mg/kg (46). Acute dermal studies show these materials have alow potential for absorption through the skin in acutely toxic amounts. No evidence of carcinogenicity has been found in animals or humans for advanced DGEBPA resins (47,48). 

The results of metabolism studies with laboratory animals and livestock indicate that endosulfan does not bioconcentrate in fatty tissues and milk. Lactating sheep administered radiolabeled endosulfan produced milk containing less than 2% of the label. Endosulfan sulfate was the major metabolite in milk (Gorbach et al. 1968). A half-life of about 4 days was reported for endosulfan metabolites in milk from survivors of a dairy herd accidentally exposed to acutely toxic concentrations of endosulfan endosulfan sulfate accounted for the bulk of the residues detected in the milk (Braun and Lobb 1976). No endosulfan residues were detected in the fatty tissue of beef cattle grazed on endosulfan-treated pastures for 31-36 days (detection limits of 10 ppm for endosulfan, 40 ppm for endosulfan diol) the animals began grazing 7 days after treatment of the pastures. Some residues were detected in the fatty tissue of one animal administered 1.1 mg/kg/day of endosulfan in the diet for 60 days. No endosulfan residues were... 

Respiratory effects have been observed in one dermal toxicity study. Of six rabbits exposed to an unspecified amount of Cellulube 220 for an intermediate duration, one died on day 36 of weakness and dyspnea of 48-hour duration (Carpenter et al. 1959). Respiratory effects were not observed in rabbits dermally exposed to 1,000 mg/kg of cyclotriphosphazene for an intermediate duration (Kinkead et al. 1989c, 1990). No acute- or chronic-duration animal studies examining respiratory tract effects were located. 

Polyalphaolefin Hydraulic Fluids. Aside from the acute lethality of inhalation exposure to certain polyalphaolefin hydraulic fluids, little is known regarding the toxic effects produced by these materials. Additional animal studies to identify the possible toxic effects of exposure to these materials may provide information relevant to the investigation of methods for reducing the toxic effects. 

Kakkar et al. (1992) exposed six male Wistar rats to a single nominal concentration of 15,302 ppm for 10 min the animals were sacrificed 24 h later. Earlier studies (not presented) had shown this to be the highest concentration tolerated without any mortality or acute toxicity. Biochemical changes in the brains of these rats suggested impairment of antioxidant defenses. No other signs of toxicity were reported. The exposure was performed under static conditions, and the measurement method was not described. 

Witkin (1956) reported intravenous (i.v.), i.p., and oral LD50 (lethal dose for 50% of the animals) values for mice and rats, and i.v. LD50 values for dogs. Similar to hydrazine, the route of administration had minimal effect on the LD50 within species. Generally, monomethylhydrazine and 1,2-dimethylhydrazine appeared to be somewhat more potent in mice and rats than was hydrazine. Results of this study showed that the 1,1-dimethylhydrazine was less acutely toxic than hydrazine or the other hydrazine derivatives. 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

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