STRUCTURE ACTIVITY TEAM REPORT

CASE NUMBER: P04-0132

RELATED CASES:

CONCLUSIONS/DISCUSSIONS

TYPE OF CONCERN: HEALTH ECOTOX

LEVEL OF CONCERN: 2 3

KEYWORDS:

LIVER

UNCERT-THYROID

IRR-S UNCERT-REPRO/ONCO

AQUATOX-A,C

SUMMARY OF ASSESSMENT

FATE: Liquid LogKow = 5.16(M); S (mg/L, 25 E C) = 14.8(M); H = 1.26E-5(E)

MP (C) < -20(M); BP (C) = 266(NOMO5) based on 133 E C @ 10mm(M)
VP @ 25C (mm) = 0.12(M) LogKoc = 3.84/2.22(M/E); LogBCF = 2.13/3.27(M/E); POTW removal (%) = 80 via sorption & possible part biodeg; OECD 301C(MITI): 0%/28d: NRB; Fish BCF (carp): 127 & 134 @ 4 & 35 ppb. Time for complete ultimate aerobic biodeg = mo

PBT Potential: P2B1T2 Sorption to soils/sediments = low - moderate *CEB FATE: Migration to ground water = moderate - rapid Volatilization Halflife Rivers = 5 da; Lake (da) = 38 Atmospheric Oxidation (halflife, hrs) OH = 11

HEALTH: Absorption is moderate all routes based on analogs. There is concern for liver effects and possibly effects on the thyroid based on the submitted 28-day oral study. The PMN compound is a strong skin irritant. There is uncertain concern for reproductive effects; and uncertain concern for oncogenicity by analogy to which are both positive for cancer; are not good analogs because they are, relative to , too metabolically

reactive. *CEB HEALTH: Moderate concern (Inhalation and dermal).

TOXICITY DATA: negative in Salmonella and E coli negative for chromosome aberrations in CHL cells acute oral study in rats - no deaths or signs of toxicity at 2000 mg/kgacute dermal study in rats - no deaths or signs of toxicity at 2000 mg/kg 28-day oral study in rats (20, 100, 500 mg/kg) - increased liver weights and hypertrophy of the centrilobular hepatocytes, slight hypertrophy of the follicular cells of the thyroid at 500 mg/kg; NOAEL = 100 mg/kg minimal eye irritant strong dermal irritant not a dermal sensitizer,

test data for the analog, , were: rat acute oral LD50 = 1.4 g/kg with tremors, effects to liver and
effects to stomach; rat acute inhalation via nose only, 4.78 mg/L (M) of mean particle size = 3.21 microns: LC0 = 4.78 mg/L but with toxic signs; moderate eye irritation in rabbits which took 7 d to clear; mild skin irritation in rabbits; Ames test was negative; E. coli test was negative; chromosome aberration test with CHL cells was positive with dose responses for structural but not numerical aberrations; no skin sensitization in guinea pigs (M&K); rat 28-d subchronic (oral-gavage) NOAEL = 200 mg/kg/d, LOAEL = 1000 mg/kg/d based on effects to the liver and kidneys and effects to the testis and sperm;

ECOTOX: Predicted (P) and measured (M) toxicity values in mg/L (ppm) are:

fish 96-h LC50 = 6.4 P fish (M) 96-h LC30 = 3.5 M S,NadjS,M H67 fish (RT) 96-h LC50 = 2.1 M SR24,M H100 fish (RT) 96-h LC50 = 3.5 M S,M H100 daphnid 48-h LC50 = 6.7 P daphnid 48-h LC50 = 1.7 M S,M H250 green algal 96-h EC50 c = 9.3 P algal 72-h EC50 c = 0.690 M S,M H15 algal 72-h EC50 a = 0.690 M S,M H15 algal 72-h EC50 r = 1.0 M S,M H15
fish chronic value = 0.550 P SAR fish ChV = 0.200 P RT96/ACR10 daphnid ChV = 0.910 P SAR daphnid ChV = 0.200 P D48/ACR10 algal ChV c = 8.9 P SAR algal ChV EC10 c = 0.460 M S,M H15 algal ChV EC10 a = 0.540 M S,M H15 algal ChV r = 0.610 M S,M H15

Predictions are based on SARs for ; SAR chemical class = ; MW228; liquid with mp < -20 C (M) and S = 14.8 mg/L at 20 C (M); log Kow = 3.5 (ClogP); pH7; effective concentrations based on 100% active ingredients and mean measured concentrations; hardness <180.0 mg/L as CaCO3; and TOC <2.0 mg/L;high concern for toxicity based on test data

assessment factor = 10.0 CC fish = 0.020 mg/L (ppm) CC daphnids = 0.020 mg/L (ppm) CC green algae c = 0.050 mg/L (ppm)
*CEB ECOTOX: All releases to water;

Becky Jones 564-8919