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EDRI Federal Project Inventory:
The Ototoxicity of Developmental Exposure to Polychlorinated Biphenyls
- Sponsor Organization: USEPA
- Project Title: THE OTOTOXICITY OF DEVELOPMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYLS
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Previous research by a number of laboratories has demonstrated that
prenatal andperinatal exposure to PCBs and TCDD results in decreased
thyroid hormoneconcentrations during the early postnatal period in the
rat. The auditory system of therat is extremely vulnerable to
alterations in thyroid hormone status during the earlypostnatal
period, a time of ongoing cochlear development. These facts led to
thehypothesis that developmental exposure to PCBs would result in
abnormaldevelopment of the auditory system. This abnormal development
would be evidencedby alterations in the structure and function of the
cochlea. This effect would result frompostnatal "dumping" of maternal
fat stores of PCBs and subsequent depletion ofcirculating thyroid
hormone levels in the offspring during the critical period of
auditorydevelopment. Initial results demonstrated that developmental
exposure to A1254 andTCDD cause decreased thyroid hormone (TH)
concentrations during the middlepreweaning postnatal period in rats.
This is consistent with increased postnatalexposure due to lipid
mobilization during lacation by the dam. This hypothyroxenemiawas
coincident with a loss of low frequency hearing. These results with
A1254 wereconsistent with the results from the postive control PTU
study, although of a lowermagnitude of effect on both audition and
THs. Results from the BAER study in A1254rats confirmed the low-
frequency hearing loss, and more importantly indicated that
theauditory problem was a result of cochlear dysfunction. More
recently, the T4replacement study demonstrated a partial block of the
hearing loss, strengthening thelink between A1254 exposure,
hypothyroxenemia during the postnatal period and low-frequency hearing
loss. Recent work has also shown a correlation between
T4concentrations on postnatal day 14 and the extent of hearing loss,
again supporting anassociation between TH concentrations and hearing
loss. Preliminary results ofongoing cross-fostering experiments have
demonstrated that 75-80112f thehypothyroxenemia is the result of
postnatal exposure. Furthermore, corticalconcentrations of PCBs on
PND21 were similar in the peri- and post-natal groups,whereas the
prenatal group was similar to controls.
- References: Goldey,E.S., Kehn,L.S., Rhenberg.G.L. and Crofton,K.M. Effects of
developmentalhypoythyroidism on auditory and motor function in the
rat. Toxicol. Appl. Pharmacol. 135,67-76 (1995).Goldey,E.S.,
Kehn,L.S., Lau,C., Rhenberg.G.L. and Crofton,K.M.
Developmentalexposure to polychlorinated biphenyls (Arochlor 1254)
reduces circulating thyroidhormeone concentrations and causes hearing
deficits in rats.Toxicol. Appl. Pharmacol.135,77-88 (1995).
- Category: MODELS
- Subcategory: HAZARD IDENTIFICATION
- Keywords for Experimental System/Species: IN VIVO, MAMMALIAN, LABORATORY STUDY
- Keywords for Experimental Endpoints: NEUROLOGICAL, HORMONAL MEASURES, THYROID HORMONES, TISSUERESIDUE, AH
RECEPTOR
- Chemical Agents: PCBs, TCDD
- Performing Institution: Neurotoxicology Division, MD-74BNational Health Effects and
Environmental Research LaboratoryUS Environmental Protection
AgencyResearch Triangle Park, NC 27711
- Contact: Dr. Kevin M. Crofton
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