Effects of chlorite exposure on conception rate and litters of A/J strain mice.
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Biomedical subjects
Publications and source records attributed to D A Leonard.
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The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450.
This study represents the first systematic attempt to rank methemoglobin-forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose-response data for comparative purposes. Six agents that are direct-acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to least potent inducers of the bioactivated agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent-specific sensitivities are addressed.