Experiences with an advanced screening procedure for the identification of chemicals with an immunotoxic potential in routine toxicology.
The development or selection of suitable tests for immunotoxicological screening and thus for incorporation into guidelines presents some problems. Most of the tests which have been proposed for immunotoxicological investigations and most knowledge and experience in immunology are based on mouse models. The standard species in the early phase of toxicological testing, however, is the rat. Any discussion about basic tests is hampered by a paucity of data from routine toxicological and/or epidemiological studies. Here we present data obtained from an advanced screening battery on the basis of OECD guideline 407. Thirteen pesticides of early development stage had been included in this screening. Two out of these 13 compounds turned out to be cytotoxic and were picked up by the immunological parameters as being 'primary immunotoxic', i.e., immunological changes not induced by overtly toxic doses ('indirect or secondary immunotoxic'). The advantages and disadvantages of each additional test is discussed as well as the comparison of the results obtained on the basic and the extended guideline test battery. In summary, the tests described here show that a little extra effort at the screening stage can save animals, time and costs for additional testing.
Vohr
H W
HW
Institute of Toxicology/Agriculture, BAYER AG, Wuppertal, Germany.
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D004353:Drug Evaluation, Preclinical / Q000191:economics / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D017408:Guidelines as Topic; D007107:Immune System / Q000187:drug effects*; D007928:Lethal Dose 50; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
D001798:Blood Proteins; D010575:Pesticides