PMID- 2455365
OWN - NLM
STAT- MEDLINE
DCOM- 19880805
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 94
IP  - 2
DP  - 1988 Jun 30
TI  - Degeneration and regeneration of the olfactory epithelium following inhalation 
      exposure to methyl bromide: pathology, cell kinetics, and olfactory function.
PG  - 311-28
AB  - The effects of acute inhalation exposure to methyl bromide (MeBr) on the 
      olfactory epithelium of male F-344 rats was investigated by morphologic 
      examination of animals killed at varying timepoints during and following exposure 
      to 200 ppm MeBr 6 hr/day for 5 days. Cell replication rate and histopathology 
      were used to assess the kinetics of repair. In addition, olfactory function, 
      using the buried food pellet test, was assessed and the result compared with 
      morphological recovery. Extensive destruction of the olfactory epithelium was 
      evident in animals killed directly after a single 6-hr exposure to MeBr. 
      Histologic features of these lesions indicate that the primary, or most severe, 
      effect of MeBr exposure was on the sustentacular cells and mature sensory cells; 
      basal cells were generally unaffected. By Day 3, despite continued exposure, 
      there was replacement of the olfactory epithelium by a squamous cell layer that 
      increased in thickness and basophilic cytoplasmic staining over the next 2 days 
      of exposure. One week postexposure, the epithelial region was covered by a layer 
      of polyhedral, basophilic cells, and from 2 to 10 weeks postexposure, the 
      epithelium exhibited progressive reorganization to reform the original olfactory 
      epithelium pattern. By Week 10, 75-80% of the olfactory epithelium appeared 
      morphologically normal. Cell replication showed a single peak of olfactory 
      epithelial cell proliferation at Day 3 of exposure, with a labeling index of 
      14.5% compared to 0.7% in controls. Cell replication rates returned gradually to 
      control levels by Week 10 postexposure. Behavioral tests of olfactory function in 
      animals after a single 6-hr exposure to 200 ppm MeBr demonstrated a loss of the 
      sense of smell, with recovery of this function by Day 6. Exposure to 90 ppm 
      caused no observable effect on olfactory function or morphology. These findings 
      demonstrate that the olfactory mucosa is highly sensitive to the toxic effects of 
      MeBr and that olfactory epithelial cell proliferation, and possible regeneration, 
      begins and occurs rapidly even in the face of continued exposure. Cell 
      replication was most prominent in the layer of basal cells adjacent to the basal 
      lamina, supporting proposals by other workers that the progenitors of both 
      sustentacular cells and neurons reside in this location. Of interest is the fact 
      that functional recovery occurs prior to complete morphological reorganization, 
      indicating the shortcoming of utilizing olfactory morphology as an index of 
      functional integrity.
FAU - Hurtt, M E
AU  - Hurtt ME
AD  - Department of Genetic Toxicology, Chemical Industry Institute of Toxicology, 
      Research Triangle Park, North Carolina 27709.
FAU - Thomas, D A
AU  - Thomas DA
FAU - Working, P K
AU  - Working PK
FAU - Monticello, T M
AU  - Monticello TM
FAU - Morgan, K T
AU  - Morgan KT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Hydrocarbons, Brominated)
RN  - 9V42E1Z7B6 (methyl bromide)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Autoradiography
MH  - Cell Division/drug effects
MH  - Central Nervous System/*drug effects
MH  - Epithelium/drug effects
MH  - Ethmoid Sinus
MH  - Hydrocarbons, Brominated/administration & dosage/*toxicity
MH  - Male
MH  - Nasal Mucosa/*drug effects/innervation/pathology
MH  - Nasal Septum
MH  - Olfactory Pathways/*drug effects/pathology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Smell/*drug effects/physiology
MH  - Staining and Labeling
EDAT- 1988/06/30 00:00
MHDA- 1988/06/30 00:01
CRDT- 1988/06/30 00:00
PHST- 1988/06/30 00:00 [pubmed]
PHST- 1988/06/30 00:01 [medline]
PHST- 1988/06/30 00:00 [entrez]
AID - 0041-008X(88)90273-6 [pii]
AID - 10.1016/0041-008x(88)90273-6 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1988 Jun 30;94(2):311-28. doi: 
      10.1016/0041-008x(88)90273-6.