Two immunotoxicity ring studies according to OECD TG 407-comparison of data on cyclosporin A and hexachlorobenzene.
Two international ring studies were performed to develop appropriate parameters within standard toxicology study for screening of immunotoxicological potential of unknown substances. These studies followed OECD TG 407 and included a number of additional examinations. CSA was selected as model for its immunosuppressive and HCB as model for its immunostimulating effects. Reproducibility of data was defined by significant findings in at least 50% of participating laboratories. In-life clinical observations, values for WBC parameters, and changes of lymphoid organ weights suggested immune effects. Elevated IgM titers indicated increased antibody formation in HCB-exposed rats. Cellularity of T-cell compartments in thymus (medulla), spleen (PALS), and lymph nodes (paracortical zone of mesenteric and popliteal LN) were dose dependently decreased in CSA-treated rats. The numbers of follicular germinal centers were reduced in LN. HCB induced cellular proliferation in spleen marginal zones and endothelial activation in HEV of mesenteric and popliteal LN and GALT and in small pulmonary venules. Data obtained by specific immune parameters indicated immune effects; however, statistical inference was limited to low numbers of participating laboratories. In spleen, both substances decreased lymphoblast proliferation after ConA mitogen stimulation. Reduced numbers of antibody-forming cells in PFC assay indicated impaired T-cell-dependent humoral immunity by CSA, which was not seen for HCB. Altered fractions for B- and T-cell subpopulations were identified in spleen for both substances. In order to predict immunomodulatory effects of CSA or HCB, histomorphologic examination of lymphoid tissues resulted in the most reliable and sensitive data to distinguish immunosuppression and -stimulation.
Schulte
Agnes
A
Bundesinstitut für Gesundheitlichen Verbraucherschutz und Veterinärmedizin (BGVV), Berlin, D-14195, Germany. a.schulte@bgvv.de
Althoff
Jürgen
J
Ewe
Sigrid
S
Richter-Reichhelm
Hans-Bernhard
HB
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004341:Drug Evaluation / Q000331:legislation & jurisprudence / Q000379:methods / Q000592:standards; D005069:Evaluation Studies as Topic; D005260:Female; D006581:Hexachlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects*; D000922:Immunotoxins / Q000633:toxicity*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D015337:Multicenter Studies as Topic; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D013950:Thymus Gland / Q000473:pathology; D036401:Toxicity Tests, Chronic
D000922:Immunotoxins; D006581:Hexachlorobenzene; D016572:Cyclosporine