STRUCTURE ACTIVITY TEAM REPORT CBI02/03/04

CASE NUMBER: P04-0269

RELATED CASES:

CONCLUSIONS/DISCUSSIONS

TYPE OF CONCERN: HEALTH ECOTOX

LEVEL OF CONCERN: 2 3

KEYWORDS: BLOOD ACUTE-LUNG DEVEL MUTA LUNG ONCO SENS-L,S UNCERT-CARDIO/IMMUNO/ALLERGY
NEURO AQUATOX-A,C

SUMMARY OF ASSESSMENT

FATE: Solid S (mg/L, 25°C) < 0.001(E); H < 1.00E-8(E) MP (C) > 1100(M); BP (C) > 400(E); VP @ 25C (mm) < 1.0E-6(E) POTW removal (%) = 90 via sorption Time for complete ultimate aerobic biodeg > mo PBT Potential: P3B1T2 Sorption to soils/sediments = v.strong *CEB FATE: Migration to ground water = negl

HEALTH: Not absorbed through the skin as the neat material, poor absorption through the skin when in solution (based on submitted dermal sensitization study for ), poor absorption from the lung and GI tract (analog). Metal salts with very low water solubility are often more soluble in physiological fluids. Some release of was found when was stirred in water for 24 hours. To the extent that the metal ions are available there are concerns for developmental toxicity ( ); mutagenicity ( are positive for DNA effects (SCEs), cell transformation and chromosome aberrations); oncogenicity (nickel); lung overload if inhaled due to insoluble particles; pulmonary oncogenicity due to crystalline nature of PMN material; uncertain concern for cardiotoxicity ; immunotoxicity ; neurotoxicity ; and allergenicity

. was ranked as highly toxic based on an acute inhalation study where high rates of mortality was seen in all dose groups (lowest dose tested is 250 mg/m3). In a 28-day oral study, effects on blood was noted with a NOEL of 100 mg/kg. was a dermal sensitizer in the submitted study.*CEB HEALTH: Moderate concern (Dermal, inhalation, drinking water)

Test data for : negative in Salmonella and E coli negative for chromosome mutations in CHL cells acute oral study in rats - 1 of 6 died at 2000 mg/kg, dark feces, rough hair coat, squatting position, emaciation very slight eye irritant not a skin irritant dermal sensitizer, Magnusson and Kligman 28-day oral study in rats (30, 100, 300 mg/kg) - no deaths; dark feces in all dose groups; rough hair coat, squatting position, body weight decrease, especially at 300 mg/kg; increase in erythrocyte count, hemoglobin content, and packed cell volume at 300 mg/kg; prothrombin time and potassium levels increased at 300 mg/kg; NOEL = 100 mg/kg acute inhalation study in rats - high mortality rates in all dose groups (0.25, 1, 5 g/m3); labored breathing, weight loss, signs of severe respiratory irritation

ECOTOX: Predicted (P) and measured (M) toxicity values in mg/L (ppm) are: fish 96-h LC50 > 6.2 P daphnid 48-h LC50 > 1.3 P green algal 96-h EC50 > 0.160 P fish chronic value > 0.290 P daphnid ChV > 0.010 P algal ChV > 0.040 P Predictions are based on SAR-nearest analog analysis for with percent composition (worst case) adjustment to toxicity; SAR chemical class = MW>=289; solid as very fine powder with mp >1100 C (M); pH7; effective concentrations based on 100% active ingredients and mean measured concentrations of ; hardness <150.0 mg/L as CaCO3; and TOC <2.0 mg/L; high concern for toxicity as worst case as reported in the PMN assessment factor = 10.0 concern concentration = 0.001 mg/L (ppm) *CEB ECOTOX: All releases to water with CC = 1 ppb

SAT Co-chair: Leonard Keifer 564-8916