Im researching the above and do not understand the dose response graph supplied (See file attached)  or the following statement made in respect to the following:

"Chlorantraniliprole exhibits few to no acute toxicological effects following single doses as high

as 5000 mg/kg and following repeated doses as high as the limit dose (1000 mg/kg). The only

consistent findings in feeding studies with chlorantraniliprole has been a mild and slight increase (approximately 20% from control) in liver weight observed in the subchronic oral rat, mice, and dog toxicity studies and the rat 2-generation reproduction study.

This observation is considered a physiological response to metabolism. Other findings include a slight reduction in body weight gain at the high dose in a 28-day dermal toxicity study in rats and a slight reduction in F1 pup but not F2 pup weight during lactation at a high dose level of 20,000 ppm when the P1 females received dietary doses equivalent to 3118 mg/kg/day.

This change in F1 pup weights was without subsequent effects post-lactation since overall weight gains and development in the F1

rats fed 20,000 ppm were similar to control animals.

The only other consistent, treatment related observation across the mammalian toxicology

studies (reported primarily in male rats) was an increased degree of microvesiculation of the

adrenal cortex after dermal or dietary administration of chlorantraniliprole.

This histologic change was observed in several rat studies including a 28-day dermal study, a 90-day oral study, a multigeneration reproduction study and at the 1- and 2-year intervals of a 2-year chronic study.

The histologic grading of increased microvesiculation in affected groups was mild. While

clearly treatment related, the slight microvesiculation of the adrenal cortex is not considered toxicologically significant.

The effects noted in the EUP toxicology database are not toxicologically significant adverse

effects, and do not indicate a hazard concern.

Subsequently, risk assessments have not been

conducted.

However, in order to characterize exposure in light of the information provided in the toxicology database, exposure has been estimated and compared to the limit doses in the mammalian toxicity studies."

Does any of this take into account long term studies of accumulative toxicity?  

Also as this chemical affects the ryanide receptors causing a flooding of calcium how would that be assessed in vitro against human cells ie what cells would be utilised and is there such an assay available?  And if no testing was done in this respect why?