Often high airflow rates or air change rates per hour (ACH) for laboratory spaces are specified to cover the risk of chemical exposure. This paper with the help of steady state isothermal Computational Fluid Dynamics (CFD) analysis investigates the impact of ACH and the location of a room return on the flow path of contaminants and resulting spatial distribution of contaminant concentration under a chemical spill scenario. The ventilation effectiveness of the HVAC system is analyzed with the help of two non-dimensional indices: Concentration Ratio (CR) and Spread Index (SI). CR normalizes the concentrations with respective to target concentration whereas SI quantifies the percent of the room volume presumed to be the high risk zone, where the CR value is greater than one. A total of five ACH levels varying from 4 to 12 are analyzed for a ceiling return. Additionally the effect of low wall return is analyzed for the lowest supply air flow rate of 4ACH. These analyses indicate with increasing ACH the concentration levels in the space decrease, however, the flow path of the contaminants remains almost similar. Also the CR and SI values do not vary significantly with ACH and remain almost constant for a certain HVAC configuration. In the case of ceiling return the maximum and average CR values at a breathing zone level were 5.4 and 1.26, respectively which indicate for a range of supply airflow rates the maximum concentrations were about 5 times higher and the average concentrations were about 26 percent higher than their respective target concentrations. Similarly the average SI value was 0.43 indicating about 43 percent of the room space was covered by the contaminants with concentrations higher than the target concentration. This study further demonstrates by changing the high ceiling return to a low wall return can significantly improve the ventilation effectiveness even at low ACH. The maximum and average CR values were reduced to 3.9 and 0.6, respectively and the SI value reduced to 0.1. This study indicates that the flow path of the contaminants plays an important role in determining the ventilation effectiveness which is primarily dependent upon the HVAC configuration. High ventilation effectiveness can be achieved even at low ACH by strategically designing the ventilation system.