SAT ReportPMN Number:P-13-0773SAT Date:8/9/2013Print Date:8/30/2013Related cases:Health related cases:Ecotox related cases:Concern levels:Type of Concern:HealthEcoCommentsLevel of Concern:23PersistenceBioaccumToxicityComments1 12Exposure Based Review:Health:Ecotox:YesRoutes of exposure:Health:Dermal Drinking Water InhalationEcotox:All releases to waterFate:;Keywords:Keywords:MUTA; ONCO; DEVEL; AQUATOXSummary of Assessment:Fate:Fate Summary:P-13-0773FATE:Solid with MP = 180-181 C (M)log Kow = 0.08 (E)S = 7.82 g/L at 25 C (E)VP = 1.7E-4 torr at 25 C (E)BP = 276 C (E)H < 1.00E-8 (E)log Koc = 1.00 (E)log Fish BCF = 0.50 (E)log Fish BAF = -0.02 (E)POTW removal (%) = 50-90 via biodeg; OECD NS: 1.0(low), 10.0 (high)/24h & 7d NRB.Time for complete ultimate aerobic biodeg = wkSorption to soils/sediments = lowPBT Potential: P1B1*CEB FATE: Migration to ground water = negl - slowHealth:Health Summary:Not absorbed through the skin as the neat material, moderate absorption through the skin if insolution; moderate absorption from the GI tract and good absorption from the lung (pchem). Concern for mutagenicity based onsubmitted test data and oncogenicity and developmental toxicity based on aromatic amines.Test Data:(-) Salmonella with and without activation; (-) E. coli with and without activation; (+) in a ratlymphoma assay without activation; rat oral LD0 = 2000 mg/kg; rat dermal LD0 = 2000 mg/kg; no eye irritation in rabbits; no skinirritation in rabbits; (-) for skin sensitization in a mouse local lymph node assay up to 75% aiEcotox:Test OrganismTest TypeTest End PointPredictedMeasuredCommentsfish96-hLC50480> 133NOEC = 133acceptabledaphnid48-hLC501.2no data providedgreen algal96-hEC505.1> 121 mg/LNOEC = 121 mg/Lacceptablefish_chronic value2.8daphnid_chronic value0.069algal_chronic value7.6Sewage Sludge3-hEC50_Sewage Sludge_Chronic Value_Ecotox Values Comments:Predictions are based on SARs for unhindered anilines; SAR chemical class = aniline-unhindered;MW 155; log Kow = 0.08 (EPI); solid with mp = 181 C (M); S = 7.66 g/L at 20 C (P);pH7; effective concentrations based on 100%active ingredients and mean measured concentrations; DWhardness <150.0 mg/L as CaCO3; and DWTOC <2.0 mg/L;Ecotoxicity Data Review for: P-13-0773Chemical Name: 2,5 Dimethoxy-4-PyrimidinamineTest Material Name: 4-Amino-2,5-dimethoxypyrimidineCASRN: 6960-17-4Trade Name: 4-ADMP, Dimethoxy Aminopyrimidine 20th, August 2013Two ecotoxicity studies were submitted with the PMN P13-0773 froma 96-hour acute fish toxicity test and a 96-houralgae growth inhibition test. The studies were conducted in 2013 and the substance was described as a solid with an estimated Log Pvalue of 0.08, an estimated water solubility of 7.66 g/L, and purity = 99.5%. The studies were performed under GLP conditions with asigned quality assurance statement and certificate of analysis also provided. Both tests followed OECD and OPPTS Guidelines forTesting of Chemicals (203 and 201; 850.1075and 850.4500 for 1) water quality parameters; 2) species, age, size, and 3) loadingrates.For the fish test, to prepare the test solutions, the test substance was directly added to laboratory dilution water. Aliquots containing1800 mg of the test substance were dispensed into approximately 15 L of dilution water to achieve a target (nominal) testconcentration of 120 mg/L. Test solutions were stirred on a magnetic stir plate utilizing a Teflon coated stir bar to mix (~3 hrs). Thesolutions were allowed to equilibrate to test temperature prior to exposure initiation. For the algal test, to prepare test solutions, aprimary stock solution was prepared at the highest test concentration of 120 mg/L. The test material (0.2400 g) was weighed into atared scintillation vial. The vial was then filled approximately halfway with AAP, capped, shaken vigorously to mix, and then addedto a 2-L volumetric flask. This was repeated until no visible test material remained in the vial. The flask was brought to volume withAAP and stirred on a magnetic stir plate using a Teflon lined magnetic stir bar for approximately 2 hours. The primary stock solutionwas clear and colorless. The primary stock was then diluted to achieve the remaining nominal concentrations. The flasks werestoppered and shaken vigorously until the solution appeared homogenous.96-hour Acute Fish Toxicity TestA 96-hour fish toxicity test in rainbow trout (Oncorhynchus mykiss) was conducted under static conditions. Following a preliminaryrange-finding test, three replicates of ten O. mykiss were exposed to laboratory dilution water (control) or the test substanceat anominal concentration of 120 mg/L in a limit test at a light intensity of 675-844 lux with a photoperiod of 16:8 light: dark.Corresponding mean measured concentrations of < LOQ (water control) and 133 mg/L were determined via LC/MS analysis (LLQ =0.00119 mg/L). Each test vessel was loosely covered to reduce evaporation. Measured concentrations of test substance ranged from109 to 115% of nominal on day 0 and 107 to 116 % of nominal on day 4. Over the course of the study, temperature = 13 to 14oC,pH= 6.7 to 7.5, DO = 6.4 to 9.5 mg/L, and water hardness = 60 to 62 mg CaCO3/L. A loading rate of 0.907 g fish/L was calculatedandmean length was 5.3 cm. Fish were observed at 0, 24, 48, 72, and 96 hours after test initiation. During the study, no fish mortality orsub-lethal effects were observed at any concentration tested, including the control.96-hour LC50 > 133 mg/LNOEC = 133 mg/L96-hour Algae Toxicity TestA 96-hour growth inhibition test with freshwater green alga (Pseudokirchneriella subcapitata) was conducted under static conditions.Following a preliminary range-finding test, five replicates of P. subcapitata (1 x 104 cells/mL) were exposed to the test substance atnominal concentrations of 0, 3.75, 7.5, 15, 30, 60 and 120 mg/L. Corresponding mean, measured concentrations of >LLQ, 3.50, 7.22,14.6, 29.5, 60.2, and 121 mg/L, respectively and were determined via HPLC/MS analysis (LLQ = 0.00119 mg/L). Additionally, sevenreplicates of P. subcapitata (1 x 104 cells/mL) were concurrently exposed to AAP medium (control). The additional replicate ateachtest and control level was not inoculated with algae to serve as a counting blank. These blanks were used to correct the dailycountsfor the interference of the test material and to monitor pH without the algal biomass. The algae were illuminated with a constant 24hour photoperiod and a light intensity of 4430-5950 lux with constant shaking (100 rpm). Test vessels were sealed with foamstoppers. Over the course of the study, temperature = 22-23oC and pH = 6.8-8.7. The 72-hour mean cell density in the controlcultures increased by a factor of 247. The testing facility listed the IC50 value (the concentration which inhibits yield by 50% relativeto the control) which is the same as the LC50.96-hour IC50 (cell yield, growth inhibition and area under the curve) > 121 mg/L96-hour NOEC = 121 mg/LConclusionBoth the fish and algal studies are considered acceptable. The preparation methods are reasonable and attempts to analyticallyconfirmthe measured PMN material in solution are done so with a precise and sensitive technique. However, without the results from anacutedaphnid test, ECOSAR (v. 1.10)predictions will be used to determine the concern concentrations due to the daphnid organismpredicted as the most sensitive. The acute concern concentration is based on the 48-hour EC50 value for daphnia of 1.2 mg/L. Thisvalue is divided by an assessment factor of 5 to yield 0.240 mg/L or 240μg/L. The chronic concern concentration is determined basedon the chronic value for daphnia of 0.069 mg/L. This value is divided by an assessment factor of 10 to yield 0.0069 mg/L or 6.9μg/L.Acute CC = 240ppb Chronic CC = 7ppbReviewer: S. PollackFactorsValuesCommentsAssessment Factor10Concentration of Concern (ppb)7SARsunhindered anilinesSAR Classaniline-unhinderedEcotox CategoryAnilinesEcotox Factors Comments:SAT Chair:L Keifer 564-8916