Teratological, neurochemical, and postnatal neurobehavioral assessment of METASYSTOX-R, an organophosphate pesticide in the rat.
The purpose of this study was to assess the embryotoxic, fetotoxic, and teratogenic potential of METASYSTOX-R (MSR) in the rat. Furthermore, the study was designed to determine if maternally toxic doses of MSR altered fetal brain acetylcholinesterase (AChE), compromised neonatal survival, growth, and development, or affected neurobehavioral development. Inseminated female rats (45/dose group) received single daily oral doses of 0, 0.5, 1.5, or 4.5 mg/kg of MSR from Days 6 to 15. Dose groups were subdivided into three termination phases: Phase I, 5 females terminated on Day 16 of gestation; Phase II, 28 females terminated on Day 20 of gestation; Phase III, 12 females terminated on Day 21 postpartum. MSR produced a dose-related reduction in maternal plasma (30-72%), red blood cell (18-56%), and brain (21-68%) cholinesterase (ChE) activity, when measured on Day 16 of gestation. The high dose of MSR significantly (p less than or equal to 0.05) reduced food consumption, suppressed body weight gain, and produced tremors in 98% of the dams. MSR administered at maternally toxic doses as high as 4.5 mg/kg was devoid of embryotoxic, fetotoxic, and teratogenic effects. Fetal brain AChE was not substantially different from control for any dose level in Day 20 fetuses. Furthermore, neonatal survival, growth, and development were unaffected and an extensive neurobehavioral testing scheme demonstrated no alteration of sensory or reflex functions, maze learning ability, or open field activity for neonates.
Clemens
G R
GR
Toxicology Department, Miles Laboratories, Incorporated, Elkhart, Indiana 46515.
Hartnagel
R E
RE
Bare
J J
JJ
Thyssen
J H
JH
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002802:Cholinesterases / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D007858:Learning / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects
D007306:Insecticides; D009946:Organothiophosphorus Compounds; C026086:methyl demeton; D002802:Cholinesterases