PMID- 9253010
OWN - NLM
STAT- MEDLINE
DCOM- 19970924
LR  - 20190920
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 19
IP  - 4
DP  - 1997 Jul-Aug
TI  - Developmental neurotoxicity evaluation of the avermectin pesticide, emamectin 
      benzoate, in Sprague-Dawley rats.
PG  - 315-26
AB  - The potential of emamectin benzoate (EB) to cause developmental neurotoxicity in 
      Sprague-Dawley rats was assessed using a study design by the US EPA. Dosages of 0 
      (deionized water), 0.1, 0.6, or 3.6 mg/kg/day were administered at 5 ml/kg by 
      oral gavage from gestational day (GD) 6 to lactational day (LD) 20 to groups of 
      25 mated females each. Between GD 17 and 20 the high dose was reduced to 2.5 
      mg/kg/day because of pup tremors observed at this dose level in a concurrent 
      two-generation study. Females were allowed to deliver and the young were 
      evaluated for survival, growth, development, behavior, and histological changes 
      to brain, spinal cord, peripheral nerve, and skeletal muscle. Behavioral 
      assessment of the offspring consisted of open field motor activity, auditory 
      startle habituation, and passive avoidance tests; each was conducted on weanling 
      and adult animals (one animal/sex/litter). Histopathological examination of the 
      CNS and PNS was conducted on one animal/sex/litter on postnatal days (PND) 11 and 
      60. There were significant increases in average F0 maternal body weight gains 
      during gestation in the 0.6 and 3.6/2.5 mg/kg/day groups, but no other effects 
      were observed in pregnant females of these or the low-dose groups during the 
      study. Beginning on PND 6, tremors were observed in high-dose pups, and this was 
      followed by hindlimb splay in all high-dose pups by PND 15-26. Both of these 
      physical signs disappeared by PND 34 (i.e., 10-11 days after weaning). There were 
      no compound-related deaths in F1 offspring. Beginning on PND 11, progressive 
      decreases in preweaning average weights were observed in the high-dose group (to 
      42% below control in females on PND 21). Average weight gain during the 
      postweaning period was significantly decreased in the 3.6/2.5 mg/kg/day group. 
      There were EB-related effects in behavioral tests only in the high-dose group. A 
      significant increase in PND 13 average horizontal motor activity was due to 
      stereotypical movements. Average horizontal activity was decreased on PND 17 and 
      in adult females, but there was no effects on PND 21. Average peak auditory 
      startle response amplitude was decreased on PND 22 and in adults. There were no 
      EB-related effects in the passive avoidance test, relative brain weights, or in 
      the histological examination (including morphometry) of the nervous system. These 
      results demonstrate that the high-dose EB exposure during gestation and lactation 
      to rats produced evidence of neurotoxicity in the F1 offspring, and a clear No 
      Observed Adverse Effect Level (NOAEL) for developmental neurotoxicity of EB was 
      determined to be 0.6 mg/kg/day.
FAU - Wise, L D
AU  - Wise LD
AD  - Merck Research Laboratories, Department of Safety Assessment, West Point, PA 
      19486, USA. david_wise@merck.com
FAU - Allen, H L
AU  - Allen HL
FAU - Hoe, C M
AU  - Hoe CM
FAU - Verbeke, D R
AU  - Verbeke DR
FAU - Gerson, R J
AU  - Gerson RJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Insecticides)
RN  - 70288-86-7 (Ivermectin)
RN  - HVM3G4A01W (emamectin benzoate)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Body Weight/drug effects
MH  - Brain/*drug effects/growth & development/pathology
MH  - Female
MH  - Guidelines as Topic
MH  - Insecticides/*toxicity
MH  - Ivermectin/*analogs & derivatives/toxicity
MH  - Male
MH  - Motor Activity/drug effects
MH  - Nervous System Diseases/*chemically induced/physiopathology
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - S0892-0362(97)00002-0 [pii]
AID - 10.1016/s0892-0362(97)00002-0 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 1997 Jul-Aug;19(4):315-26. doi: 
      10.1016/s0892-0362(97)00002-0.