Developmental neurotoxicity of methanol exposure by inhalation in rats
Weiss, B; Stern, S; Soderholm, SC; Cox, C; Sharma, A; Inglis, GB; Preston, R; Balys, M; Reuhl, KR; Gelein, R
HERO ID
79211
Reference Type
Technical Report
Year
1996
Language
English
PMID
| HERO ID | 79211 |
|---|---|
| Year | 1996 |
| Title | Developmental neurotoxicity of methanol exposure by inhalation in rats |
| Authors | Weiss, B; Stern, S; Soderholm, SC; Cox, C; Sharma, A; Inglis, GB; Preston, R; Balys, M; Reuhl, KR; Gelein, R |
| Publisher Text | Health Effects Institute |
| City | Boston, MA |
| Volume | 73 |
| Page Numbers | 1-64; discussion 65-70 |
| Abstract | The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm)* (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (CD) 6 with both dams and pups then being exposed through postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 g/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified. Neurotoxicity was assessed primarily by behavioral tests used previously to reveal adverse effects following developmental exposures to ethanol, cocaine, heavy metals, and many other agents. Male-female pairs from identical litters were entered into the statistical analysis, whenever appropriate, to examine gender differences. Suckling latency and attachment, odor discrimination, and spontaneous activity were measured before weaning. At 90 to 267 days of age, depending on the cohort, the offspring received training in either of two types of schedule-controlled operant behavior. One schedule required them to rotate a running wheel a specified number of revolutions to secure food pellets, which reinforced the behavior. It was included both as an index of motor function and as an index of responsivenessto the contingencies built into the reinforcement schedule. The primary measure of performance consisted of the number of responses (revolutions) per one-hour session. The other schedule consisted of a complex stochastic spatial discrimination task and was included as an index of cognitive function. In an operant test chamber containing threelevers, contingencies were arranged so that the probability of food pellet reinforcement for a response on any particular lever depended on which of the three levers had been the site of the previous response. The primary measure was based on the extent to which the subjects maximized pay-offs for lever-pressing. Exposure to methanol did not affect suckling latency and attachment on PND 5, or performance on the conditioned olfactory aversion test on PND 10. Exposure to methanol did alter performances in the motor activity test. Methanol-exposed neonates were less active on PND 18, but moreactive on PND 25 than the equivalent control-group pups. Schedule-controlled running displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. The results of the complex stochastic reinforcement schedule also revealed behavioral differences due to methanol exposure; these were relatively subtle in nat |
| Pmid | 11379053 |
| Report Number | HEI Research Report Number 73 |
| Is Certified Translation | No |
| Dupe Override | No |
| Number Of Pages | 80 |
| Comments | ECRIB.Cambridge, MA: Health Effects Institute; research report no. 73. |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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