###### Abstract
Some widely used solvents are hexane, acetone, ethanol, methanol, isopropanol, butanol, chloroform, and pentane. [PERSON] et al. (1952) reported that the butanone-water pair containing 10% of water can reduce free gossypol to 0.054% [18]. [PERSON] et al. (2012) used ethanol for the removal of gossypol from defatted cottonseed at a temperature below 323 K that could reduce 62% gossypol [20]. [PERSON] and [PERSON] (1981) investigated the use of methylene chloride for the reduction of FG and TG from defatted cottonseed meal. Authors suggested that low levels of water and acetic acid in propylene glycol aided methylene chloride to reduce FG and TG up to 0.013% and 0.15%, respectively [11]. [PERSON] et al. (2019) used a mixed solvent comprised of butanol-ethanol-water (80:15:5 v/v) acidified with 0.5 M oxal acid. The experiment was performed at a solvent-to-seed ratio of 15, extraction time 180 min, and temperature 348 K. In their study, they could reduce 94% gossypol from defatted cottonseed meal [8]. Among the various extraction methods, extraction with acetone was found a desirable choice to reduce FG from cottonseed meal [21]. In a study, a mixture of acetone and n-hexane was used to reduce gossypol from cottonseed flakes and found that 25% acetone has reduced FG by 90% [22]. In another study, a mixture of acetone, ethanol, and water acidified with phosphoric acid was applied to reduce TG from cottonseed meal. The mixture solvents reduced TG significantly [23]. [PERSON] et al. (2007) also observed that aqueous acetone is effective for the reduction of FG to a very low level using a two-stage solvent extraction process that provides 72% protein concentrate [2]. [PERSON] and [PERSON] (1967) revealed that acetone containing 25-30% water removes a maximum of 96% of FG, most of the free fatty acids, about half the raffinose, negligible quantity of oil and protein from cottonseed flakes at temperature 25-30 \({}^{\circ}\)C. Other parameters such as successive extraction, liquid-to-solid ratio (LSR), temperature, time, pressure, and pH affect the gossypol reduction as well [24]. [PERSON] et al. (2015) studied the effects of important parameters such as temperature, solvent to solid ratio, time of extraction, and extraction efficiency. The author reported that these input factors greatly affect the extraction of gossypol from the cottonseed meal [25]. Similarly, [PERSON] et al. (2006) performed the experimental investigation to determine the optimal process parameters such as for the reduction in gossypol level in cottonseed meal [14]. Although numerous attempts have been made for gossypol reduction, mainly FG from cottonseed meal; however, very few studies have been reported for TG reduction from cottonseed kernel to a safe level that is fit for human and animal feed. The TG may be toxic to the monogastric animals if its hydrolysis takes place by getting favorable conditions in the stomach, such as a low pH environment. In addition, studies on the combined effects of effective parameters on gossypol reduction are not available. Moreover, no study has been performed for the preparation of prediction models that can predict the FG and TG percentage reduction in the cottonseed kernel powder (CSKP). In the present investigation, experiments were conducted to reduce both FG and TG to the minimum level. Response surface methodology (RSM) based approach was conducted to determine the combined effects of various process parameters viz. acetone level, time, LSR, and the number of extraction cycles on FG and TG reduction percentage. In continuation of this, a quadratic regression model for predicting the FG and TG reduction percentage was developed. Analysis of Variance (ANOVA) has been performed to determine the highly significant parameter. Finally, the optimal parametric combination of input variables that provide better FG and TG percentage reduction is determined by the RSM-based desirability approach. RSM is a collection of mathematical and statistical techniques that are useful for modeling and analysis of various problems.