In cytotoxicity study, it is possible that in vitro cell responses will vary depending on the cell lineage. This consequently affects the toxicity ranking and the threshold levels considered safe for use. This study aims to examine the probable variations in the cytotoxic effects elicited by rubber chemical additives evaluated against three different cell lines, U937 (monocytic), HeLa (epithelial) and L929 (fibroblastic) cells. Additives tested were zinc diethyldithiocarbamate (ZDEC), zinc dibutyldithiocarbamate (ZBUD), zinc-2-mercaptobenzothiazole (ZMBT), zinc oxide (ZnO) and 2,2-methylene-bis(4-methyl-6-tert-butylphenol) (2246). Cell response was quantified using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, which measures the cell metabolic activity via the reduction of MTT salt by dehydrogenase enzymes in living cells. Results show that ZDEC was least tolerated by all three cell lines, followed by ZBUD, while the toxicity ranking of ZMBT, ZnO and 2246 changes depending on the types of cell. The lethal chemical concentrations (LC50) against the three cell lines were constant for ZDEC and ZMBT, but varied for ZBUD, ZnO and 2246. This indicates celldependent toxicity among some of the rubber chemical additives. Caution should therefore be excercised when using these toxicity threshold values to gauge the safety levels for use.