Evaluation of the Immunotoxicity of {eta}-Hexachlorocyclohexane ({eta}-HCH)

Evaluation of the Immunotoxicity of-Hexachlorocyclohexane -HCH).CORNACOFF, J. B., LAUER, L. D., HOUSE, R. V., TUCKER, A. N.,THURMOND, L. M., VOS, J. G., WORKING, P. K., AND DEAN, J. H.Fundam Appl. Toxicol. 11,293–299.0-HCH, an isomeric contaminantformed during the manufacture of the insecticide lindane, isa persistent environmental and food chain pollutant which hasbeen reported to exhibit estrogenic activity in rodents andin fish. To investigate potential toxic effects on the reproductiveand immune systems, -HCH was fed to female B6C3F1 mice for 30days. Mice exposed to 0, 100, or 300 mgo-HCH/kgofdiet were evaluatedfor changes in ovarian and uterine histology, body weight, lymphoidorgan weight and histology, splenic cellularity, antigen-specificIgM and IgG plaque-forming cells (PFQ, proliferative responsesto mitogens, natural killer (NK) cell activity, and inductionof cytolytic T lymphocytes. The ovaries and endometrial epitheliumexhibited normal architecture. No alterations were observedin body weight, lymphoid organ weight and histology, or spleniccellularity whereas significant changes were found in severalimmune functions at the 300 mg/kg dose. Proliferation of splenocytesto the mitogens LPS, PHA, and Con A was decreased by 39,43,and 57%, respectively. T-lymphocyte-mediated cytolysis of tumortargets was decreased by 25% with a concurrent reduction of45% in NK activity. There was no significant reduction in thenumber of IgM or IgG PFC in exposed animals. These data indicatethat -HCH causes nonestrogenic immune function changes in theadult mouse without gross changes in lymphoid organ weight,histology, or cellularity.     

Comparison of a Radioisotopic Incorporation method and the Mouse Ear Swelling Test (MEST) for Contact Sensitivity to Weak Sensitizers

Comparison of a Radioisotopic Incorporation Method and the MouseEar Swelling Test (MEST) for Contact Sensitivity to Weak Sensitizers.CORNACOFF, J. B., HOUSE, R. V. AND DEAN, J. H. (1988). Fundam.Appl. Toxicol. 10, 40-44. A radioisotopic incorporation assayutilizing [¹²⁵I]iododeoxyuridine was compared to the standardmouse ear swelling test (MEST) for the strong sensitizers dinitrofluorobenzeneand oxazolone, and for the three weak sensitizers ethylenediamine(EDA), glutaraldehyde, and nickel sulfate. Mice were sensitizedepicuta-neously on the abdomen for 4 consecutive days priorto challenging the left ear with the test agent and the rightear with the vehicle. A comparison of the mean difference betweenthe test and the control ears showed that measuring reactivity48 hr postchallenge on Day 7 is the most sensitive time periodin the radioisotopic incorporation method. Both the isotopicand MEST assays gave positive results with the potent sensitizers,although the response detected by isotopic labeling of emigratingcells was up to 1000-fold greater than that determined by earswelling measurements. No response was detected to the moderateto weak sensitizer EDA in either assay. Reactivity to glutaraldehydewas not detected by the radioisotopic assay but was minimallyresponsive and significant by the MEST. The opposite was truefor nickel sulfate where minimal but significant reactivitywas seen in the isotopic assay but not in the MEST. Althoughthe radioisotopic assay had the advantages of being more quantitativeand of having improved sensitivity, it was of no greater valuethan the MEST for detecting weak sensitizers. It was concludedthat the mouse was not a suitable model for routinely detectingreactivity to weak sensitizers regardless of which of the twoassays were used.