Collaborative studies on cytogenetic and dominant lethal assays

Two in vivo cytogenetic studies and one dominant lethal study were jointly conducted by members of government, academic, industrial, and independent commercial laboratories between 1970 and 1975 to determine the validity and reproducibility of the techniques. The cytogenetic studies consisted of preparations and analyses of bone marrow cells from male rats for chromosome abnormalities. In the first study, participants from 4 laboratories jointly prepared slides at a Food and Drug Administration (FDA) laboratory according to a prescribed procedure and independently analyzed the slides in their own laboratories. In the second study involving 6 laboratories, a workshop was held at Dow Chemical Co. to reduce scoring differences and to develop a joint protocol. All participants then independently performed the exact procedure in their own laboratories, using animals from a common source. In the dominant lethal study involving 6 laboratories, a workshop was held at the FDA to discuss protocol and to practice the technique. All participants then independently conducted the study in their own laboratories using rats and test chemicals from common sources. In all 3 studies, significant interlaboratory variability existed, and the differences varied with the parameters analyzed.