EA Review #2, NDA 20-358                                                                                                                               Page 2

 

iii.             Sufficient information has been provided regarding the disposal firms.    ADEQUATE

 

7.a.      A discussion of the polarity of the peaks observed in the photodegradation studies has been added.  Four of the 5 peaks are more polar.  One peak is less polar but it is believed to be a process impurity than a degradant since the peak was less than 1% throughout the studies.  ADEQUATE

 

7.b.      The requested literature reference is included.  ADEQUATE

 

7.c.      The requested literature reference has been provided.  They did not discuss any significant deviations from the EATAD, but review of the information submitted indicates that the procedure used was typical scientific practice.  ADEQUATE

 

7.d.      A statement that there were no significant deviations was included.  ADEQUATE

 

7.e.      The company could not find a literature reference to support the octanol water partition coefficient.  The first reviewer’s concern was that the testing was conducted prior to the issuance of the EATAD and did not follow the procedure (e.g., single determinations vs. multiple).  This reviewer suggested they use the equation included in the ETAD that relates solubility to the octanol water partition coefficient.  The company did this but did not include the information in the EA because the calculated values were significantly different from the experimental values.  Although they were different it should be noted that both the experimental and calculated values indicate the material is not lipophilic, therefore bioconcentration or adsorption to soil are not a concern.  ADEQUATE

 

7.f.       The document has been revised to indicate that the material is inherently photolabile but the rate would depend on environmental conditions.  ADEQUATE

 

8.              The company was asked to search the literature and report available test data and also report any

mammalian toxicity information.  A computerized structure activity relationship modeling program could be used to supplement the literature information.  As requested the company supplied the information.  A computerized structure activity relationship program was unavailable.  The company addressed the issues.  ADEQUATE

 

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