STRUCTURE ACTIVITY TEAM REPORT CBI 02/03/04

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