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

Amendment 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 REREGISTRATION 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-Dichlorophenoxyacetic acid: Acute 

Neurotoxicity Study in Fischer 344 Rats. The Toxicology Research Laboratory, Dow Chemical Co.; Study No. 

K-002372-066, January 5, 1994. MRID 43115201. Document No. 011273. Unpublished. 

EXECUTIVE SUMMARY: In an acute neurotoxicity study [MRID 43115201], Fischer 344 rats (10/sex/dose) 

were orally gavaged 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). Neurobehavioral 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 15), 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 Day 4 in males and Day 5 in 

females. 

Neurobehavioral evaluation revealed treatment-related changes. During the Day 1 FOB 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). Slight gait abnormalities, 

observed in a single mid-dose female, were not judged to be treatment-related since no other signs of toxicity

were evident. Minimal [equivocal] gait abnormalities, not judged to be treatment-related, were observed in one 

low-dose female and one each mid- and high-dose male. In high-dose animals, total motor activity was 

significantly lower at Day 1 only. 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 NOAEL 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 study in the rat.