Document GKnp4oLRbXJgpDrRDKKgda9YY

EID217052.TIF (2544x3266x2 tiff) $rom: CAVANARJ--ISCDCVM1 To: DEVOEDtf --ISCDCVM1 David W. DeVoe Date and time 11/04/94 13:15:25 ADATOY --ISCDCVM1 Yasef Adato From: Robert J. Cavanaugh 999-4385 Subject: RE: HP in Shaving Product See the attached note from Gerry Kennedy on C-8 levels from exposure to shaving cream. There is one error in them:the concentration of C-8 is 20 ppm in the MP-1600, not in the shaving gel. The anticipated level of MP-1660 is 1% in Edge, thus Gerry's numbers are high by 100X. In spite of this, I agree with his conclusion that this is a risky area. A dally application rate of 2 micrograms is still one third of the CEG. Another way to look at this is to calculate the steady state level of C-8 in the blood. At equilibrium, 2 micrograms will be absorbed per day and 2 micrograms will be eliminated. The half life of C-8 in the body is about 3 years. The first order rate equation is Ln(Cl/C2) -kt where C is the concentration, k is the rate constant and t is time. For the half life, C1/C2 - 2 and k can then be calculated to be 0.000633/day. From this, you can calculate that to eliminate 2 micrograms per day, there must be 3160 micrograms present. In 5 Kg of blood, this would be 0.63 ppm. This is starting to get a little close to the level which concern us. I believe these are a few ppm (GERRY: is this correct?). My recommendation is to stay away from this application. We're getting near the concern limit on C-8. PTFE may be an excellent dry lubricant but I question how well it will working in a gel which is already lubricated. There may be some applications where skin contact would be acceptable. One would be in the PTFE/Krytox grease as a nerve agent repellant. This is not a repeated use application and I would prefer to take my chances with 2 micrograms of C-8 rather than a gram of Sarin. Let me know your thoughts on this as we have to get back to First Brands. *** Forwarding note from BUXTONLW--ISCDCVM1 11/03/94 16:40 *** To: CAVANARJ--ISCDCVM1 Robert J. Cavanaug from: Bill Buxton, FLPR Reg Affairs, CR/713/110 (99-94658) Subject: RE: MP in Shaving Product Bob, Attached is a calculation of potential exposure level to C-8 based on your initial assumptions. Note the Gerry also assumes 100% transfer at each step. Overall, this does not look like a good use for this product. Let me know if you have further questions..... Bill. *** Forwarding note from KENNEDY --HSKVAX 10/24/94 09:10 *** Subj: RE: MP in Shaving Product From: To: NAME: GERALD L KENNEDY FUNC: CR&D TEL: 366-5259 NAME: BUXTONLWISCDCVM1 <KENNEDY AT A1 AT HSKVAX> HERE IS MY SAMPLE CALCULATION WHICH I THINK SUGGESTS THAT WE MOVE SLOWLY INTO THIS APPLICATION. / U j1) C-8 IN EDGE -,2,0PPM, OR 20,0 MICROG/10 GRAM EDGE APPLICATION 000181 E1D217052 LWB000678 EID217053.TIF (2544x3265x2 tiff) 'w K ^ 100 DERMAL m s s FIS. EQUALS DAILY DOSE OF 2,00 MICROC/DAY I) 0UI CSC IS 0.0003 MC/K3;DAILY AIK EXCHANGE OF 20 K3 FUSSENTS 0.006QMC Ot H1CX0GRAKS TO THE LUNG. 4)TH! DAILY ALLOWED INHALATION DOSE THEM BECOMES (IF THIS MATH IS RIGHT) ABOUT 30-33 TIKIS LESS THAN THE AMOUNT PRESENTED TO THE SKIN IN ONE AFFLICATION OF IDOt. i)ANOTHER HAY TO LOOK AT THROUGH BLOOD KINETICS 6) 70KG PERSON IS ABOUT 7 BLOOD OR 3 KG BLOOD 7) C-S DOCS GET TO AND STAY IN BLOOD-ASStMl TOTAL TRANSFER FROM ONE EDGE APPLICATION TO BLOOD- 200 MICROC/5 RC BLOOD AO MICROG/KO - 40 PFB 8) WITH A 1/2 LIFE IN YEARS. SAY 3 AS BEST CURRENT ESTIMATE:STEADY STATE VOULD BE IN THE PPM RANGE (I DIDN'T,CAN'T 00 THAT CALCULATION BUT 200 MICROG /DAY WITH LITTLE CLEARANCE VOULD GET -JP THERE IN A MURKY. YOU MIGHT KANT TO 00 OVER AMD SEE IF THIS MAKES SENSE TO YOU, BUT IT GITS MB CLOSE TO OUT OF BOUNDS IN A HURRY. V cc: CAVANAEJ--ISCDCVM1 Robert Cvn*ugh KENNEDY --HSKVAX GERALD L KENNEDY Burravu--ISCDCVM1 L. U 1 1 U * Buxton LEVYD --EU0I32 DANNY LEVY TURNEEJ -E001S2 Jf C. T u m o r SELLENGA--ISCDCVK1 Gregory A. B * U n 000182