Document ID: EPA-HQ-OPP-2002-0262-0058
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-11-16T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                           WASHINGTON, D.C.  20460

TXR# 0054486

DP BARCODE: D327215

3/15/07

MEMORANDUM

SUBJECT:	PC 079401: Endosulfan – Developmental Neurotoxicity Feeding
Study in Rats with Endosulfan [MRID# 46968301]. 

 ADVANCE \d0 FROM:		David G Anderson, Ph.D., Toxicologist

and

Judy Facey, Ph.D., Toxicologist

RRB-2, HED (7509P) 

 ADVANCE \d1 TO:			Tracy Perry

 ADVANCE \d1 SRRD (7508P)

 ADVANCE \d7 THROUGH:	Mary Elissa Reaves, Ph.D., Toxicologist

RRB-2, HED (7509P)

Bayer CropScience submitted a Developmental Neurotoxicity Feeding Study
in the Rat with Endosulfan [MRID# 46968301] for the Endosulfan Task
Force [ETF]. 

Summary:  In a developmental neurotoxicity study (MRID 46968301),
endosulfan (99.1% a.i, batch# EGPC400349)] was administered to 30 female
Wistar Crl:WI (Han) rats per group in the diet at dose levels of 0,
50,150, or 400 ppm or 0, 3.74, 10.8 or 29.8 mg/kg bw/day from gestation
day 6 through postnatal day 21.

		The NOAEL for dams is 10.8 mg/kg/day.  The LOAEL is 29.8 mg/kg/day
based on decrease body weight, food consumption and food efficiency.

		There was no NOAEL for pups.  The LOAEL was the LDT at 3.74 mg/kg/day
based on decreased pup weight on PND 11 and decreased weight gain at PND
4-11.  At the MDT, possible delayed preputial separation in males
occurred.  No neurotoxic effects were seen at the LDT or MDT.  Possible
effects were shown at the HDT for PND 21 male rearing in the FOB [within
historical control range], PND 21 male fixed perfused brains and a 0.158
mm statistically significant decrease in female morphometric
measurements on the PND 21 hippocampal gyrus at the HDT, the only dose
level measured [control 1.623 mm, HDT 1.469 mm, p<0.05], but these
values in control and at the HDT were within historical control range of
1.38 to 1.69 mm.  These possible neurotoxic related effects could be
biologically significant and treatment related at higher doses, but are
not definitively shown in this study at the HDT.

	This study is classified ACCEPTABLE and satisfies the guideline
requirement for a developmental neurotoxicity study in rats (OPPTS
870.6300, 83-6); OECD 426 (draft).

COMPLIANCE:  Signed and dated GLP, Quality Assurance, and Data
Confidentiality statements were provided.