PMID- 15954087
OWN - NLM
STAT- MEDLINE
DCOM- 20051107
LR  - 20121115
IS  - 1542-9733 (Print)
IS  - 1542-9733 (Linking)
VI  - 74
IP  - 3
DP  - 2005 Jun
TI  - Effects of hyperthermia and boric acid on skeletal development in rat embryos.
PG  - 268-76
AB  - BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the 
      development of the axial skeleton have been reported previously. Both cause an 
      increased incidence of axial skeletal defects including a decrease in the total 
      number of ribs and vertebrae. Because of the similarity in the effects of the two 
      agents, we examined their interaction when given in combination to pregnant rats 
      on gestational day (GD) 10. METHODS: Dams were treated on GD 10 with BA (0, 250, 
      or 500 mg/kg) and hyperthermia (37, 41, or 42 degrees C) and allowed to deliver 
      their pups. Doses of BA were based on results from a dose-finding study. Litters 
      were evaluated on postnatal days (PND) 1 and 3 for number, gender, and weight of 
      pups. On PND3, pups were examined externally and viscerally, and double-stained 
      for skeletal evaluation. RESULTS: A dose-dependent, statistically significant 
      increase in fetal skeletal defects was seen on PND 3 with BA or hyperthermia 
      alone with even greater effects when given in combination. Defects included rib 
      and vertebral fusions, split vertebral centra in the thoracic and lumbar areas, 
      and a decrease in the total number of ribs and vertebrae. CONCLUSIONS: The 
      increased incidence of skeletal defects resulting from combined exposure to 
      hyperthermia and BA was additive for segmentation defects and synergistic for the 
      reduction in numbers of vertebrae.
FAU - Harrouk, Wafa A
AU  - Harrouk WA
AD  - Division of Reproductive and Urologic Drug Products, Center for Drug Evaluation 
      and Research, US Food and Drug Administration (FDA), Rockville, Maryland 20857, 
      USA. harroukw@cder.fda.gov
FAU - Wheeler, Kellylynn E
AU  - Wheeler KE
FAU - Kimmel, Gary L
AU  - Kimmel GL
FAU - Hogan, Karen A
AU  - Hogan KA
FAU - Kimmel, Carole A
AU  - Kimmel CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Boric Acids)
RN  - 0 (Insecticides)
RN  - R57ZHV85D4 (boric acid)
SB  - IM
MH  - *Abnormalities, Drug-Induced
MH  - Animals
MH  - Bone and Bones/abnormalities/embryology
MH  - Boric Acids/*toxicity
MH  - Embryo, Mammalian/*drug effects
MH  - Female
MH  - Fetus/abnormalities
MH  - *Hot Temperature
MH  - Insecticides/*toxicity
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spine/*abnormalities/embryology
EDAT- 2005/06/15 09:00
MHDA- 2005/11/08 09:00
CRDT- 2005/06/15 09:00
PHST- 2005/06/15 09:00 [pubmed]
PHST- 2005/11/08 09:00 [medline]
PHST- 2005/06/15 09:00 [entrez]
AID - 10.1002/bdrb.20047 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):268-76. doi: 
      10.1002/bdrb.20047.