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II. BACKGROUND and ACTION REQUESTED 

An immunotoxicity study on Propoxur (MRID# 48759401) has been submitted. RAB VI 

was asked to review and prepare a DER for this study. 

III. RESULTS AND DISCUSSION 

The immunotoxicity study in rats for Propoxur (MRID# 48759401) has been reviewed. 

The DER is attached and an executive summary is as follows: 

EXECUTIVE SUMMARY: In an immunotoxicity study (MRID #48759401), Propoxur 

Technical (99.1% a.i., Batch no. KP074PF 436-1-00006-2) was administered to male and 

female Wistar (Hsd Cpb:Wu) rats (8/dose/sex) in the diet at dose levels of 0, 1250, 2500, 

or 5000 ppm (equivalent to 0, 88.9, 175.5, or 362.6 mg/kg/day for males and 0, 103.7, 

177.5 or 342.7 mg/kg/day for females, respectively) for at least 32 days. During the 

study, clinical condition, bodyweight, food and water consumption, organ weight, macro 

and histopathology were evaluated. Five days before sacrifice, all animals in all groups 

received a single intravenous dose of sheep red blood cell (SRBC, 1x109 SRBC/mL in 

BSS, 100 μL/animal). At sacrifice on Day 28, selected organs were removed and 

weighed (brain, spleen, and thymus). The anti-SRBC antibody response was measured 

with a modified plaque forming cell (PFC) assay. In addition, flow cytometric analysis 

for subpopulation of the spleen cells and antibody (IgG, IgM, and IgA) titers with ELISA 

were measured. Positive controls were performed previously with cyclophosphamide at 

40 or 80 mg/kg/day for reliability check of these assays. 

There were no premature deaths, and no treatment-related clinical signs. Body weights 

were statistically significantly reduced since Day 14 in all treated groups in males. At 

Day 32, the differences of mean body weights in treated groups compared to the control 

were 8.4%, 8.9% and 10.8% for males and 4.3%, 9.5% and 12.6% in females (for groups 

1250 ppm, 2500 ppm and 5000 ppm, respectively). There was persistently low food 

consumption in the mid and high dose groups when compared to the vehicle control 

group. The decreases of body weight and food consumption were considered 

toxicologically significant at 5000 ppm for both sexes. The organ weights (spleen, 

thymus and brain) were not significantly different from the vehicle control group. 

Histopathology of these organs and mesenteric lymph nodes gave no evidence of 

treatment related effects. 

The systemic LOAEL was 5000 ppm (equivalent to 362.6 mg/kg/day in males and 

342.7 mg/kg/day in females) based on reduced body weight gain and food 

consumption. The systemic toxicity NOAEL was 2500 ppm (175.5 mg/kg/day for 

males and 177.5 mg/kg/day for females). 

There were no significant treatment-related effects on the specific anti-SRBC PFC 

response as measured by total activity (PFC/106

 viable cells) or total activity 

(PFC/spleen). High inter-individual variability was noted in all the treatment groups as 

well as in the control group. Evaluation of the individual animal data of this study did 
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not show any trend or distribution that would demonstrate significant suppression of antiSRBC antibody response. 

There were no significant treatment-related effects on antibody (IgG, IgM, or IgA) titers, 

and splenic cell subpopulations. In the flow cytometric analysis, females at 5,000 ppm 

showed statistically significant decrease in NK cells (CD 161+

). However, this decrease 

was within the normal range of variance for this parameter; and it was not observed in 

males. NK cell activity assay was not performed. The overall weight of evidence suggests 

that the chemical does not directly target the immune system. Under HED guidance a 

NK cell activity assay is not required at this time. 

The NOAEL for immunotoxicity was 5000 ppm (equivalent to 362.6 mg/kg/day for 

males, and 342.7 mg/kg/day for females), the highest dose tested; the LOAEL for 

immunotoxicity was not established. 

This immunotoxicity study is classified acceptable/guideline and satisfy the guideline 

requirement for an immunotoxicity study (OPPTS 870.7800) in the rats.