[2,4 -D] Acute Neurotoxicity Screening Battery - Rat [§82 - 7/OPPTS 870.6200]

Am endment to DER for MRID 43115201 - Acute Neurotoxicity Screening Battery [Rat] [2,4 -DICHLOROPHENOXYACETIC ACID] This amendment provides an EXECUTIVE SUMMARY to upgrade the original DER [Document No. 011273]. EPA Reviewer: Linda L. Taylor, Ph.D. Reregistration Branch I, Health Effects Division (7509C) EPA Secondary

Reviewer: Whang Phang, Ph.D. Reregistration Branch I, Health Effects Division (7509C) TXR# 0051360 AMENDED DATA EVALUATION RECORD STUDY TYPE : acute neurotoxicity - rat § 82 - 7/OPPTS 870.6200 P.C. CODE : 030001 REREGI STRATION CASE NO. : 818706 CASWELL NO. : 315 CAS NO. : 94 - 75 - 7 TEST MATERIAL(PURITY) : 2,4 - Dichlorophenoxyacetic acid [96.7%] SYNONYMS : 2,4 - D SPONSOR : Industry

Task Force II on 2,4 - D Research Data CITATION : Mattsson, J. L. , McGuirk, R. J., Yano, B. L. (1994). 2 ,4 - Dichlorophenox ya cetic acid: Acute Neurotoxicity

S tudy in Fischer 344 Rats. The Toxicology Research Laboratory, Dow Chemical Co.; Study N o. K- 002372 - 066, January

5, 1994. MRID 43115201. Document No. 011273. Unpublished. EXECUTIVE SUMMARY : Inan acute neurotoxici ty s tudy [ MRID 43115201], Fischer 344 rats (10/sex/dose) were orall y g avaged once with 2,4 - D [96.6% a.i.] at doses of 0 (corn oil), 15, 75, or 250 mg/kg (actual: 0, 13, 67 or 227 mg/kg). N eurobehavioral evaluations, consisting of Functional Observational Battery ( FOB) and motor activity , were conducted at Day - 1 (prestudy), Day 1 (approximately 5 - 6 hrs postdosing, peak time of effect) and Days 8 and 15. At terminal sacrifice (Day 1 5), animals were euthanized and neuropathological examination performed on control and treated animals (5/sex/dose). There were no treatment - related mortalities, and no significant differences were noted in the mean body weights or mean body- weight gains. Treatment - related, clinical signs [uncoordinated movement/behavior] were observed in the high - dose rats only . During the Day 2 and 3 clinical examinations, incoordination was noted in high - dose animals of both sexes [ Day 2 , 2/10 males and 5/10 females; Day 3 , 2/10 males, 1/10 females; Day 4 , 0/10 males, 1/10 females]. The incidence of incoordination decreased to control levels by D ay 4in males and Day

5 in females. Neurobehavioral evaluation revealed treatment - related changes. During the Day 1 F OB evaluations, increased incidences of incoordination (6/10, males; 4/10, females) and slight gait abnormalities, described as forepaw flexing or knuckling, were observed in high - dose animals (8/10, males; 8/10 females). S light gait abnormalities, observed in a single mid - dose female, were not judged to be treatment - related since no other signs of toxicity were evident. M inimal [equivocal] gait abnormalities, not judged to be treatment - related, were observed in one low - dose female and one each mid - and high - dose male. Inhigh - dose animals, total motor activity w as significantl y lower at Day 1 o nly . No treatment - related gross or neuropathological findings were present at any dose level in either sex. The NOAEL for neurotoxicity is 67 mg/kg, based on an increased incidence of incoordination and slight[2,4 -D] Acute Neurotoxicity Screening Battery - Rat [§82 - 7/OPPTS 870.6200]

2 gait abnormalities [described as forepaw flexing or knuckling] and decreased total motor activity at the LOAEL of 227 mg/kg. The NO AEL for systemic toxicity was 227 mg/kg [the highest dose tested] in males and females. This acute neurotoxicity study in the rat is classified ACCEPTABLE/Guideline, and it satisfies the guideline requirement [OPPTS 870. 6200] for an acute neurotoxicity s tudy in the rat.