Hypothalamo-pituitary-adrenal gland axis in mice inhaling toluene prior to low-level long-term exposure to formaldehyde.

We studied the change in the hypothalamo-pituitary-adrenal gland (HPA) axis upon adding prior toluene inhalation to our previous formaldehyde inhalation experiments to determine whether short term exposure to relatively high levels of toluene triggers multiple chemical sensitivity (MCS). Data come from immunocytochemical, morphometrical and RT-PCR measurements. Four groups of adult female mice were exposed to differing concentrations (0, 80, 400, and 2,000 ppb) of formaldehyde for 16 hr/day, 5 days/week for twelve weeks, after the mice were exposed intranasally to 500 ppm toluene per mouse for 6 hr/day, for 3 days. We found that the number of corticotropin releasing hormone (CRH)-immunoreactive (ir) neurons was up-regulated according to the amount of formaldehyde as well as inhalation of formaldehyde alone in our previous experiment. The proportion of adrenocorticotropin hormone (ACTH)-ir cells increased according to the formaldehyde concentration, though there was no significant difference between the 400 and 2,000 groups. The number of ACTH-ir cells was higher in the 400 group than in the other groups (0, 80, and 2,000). Expression of ACTH-mRNA was also up-regulated according to the quantity of formaldehyde. The sinusoid in the anterior pituitary showed more dilatation in the 400 and 2,000 groups than in the control group, especially in the 2,000 group. We propose that exposure to toluene prior to inhalation of formaldehyde has no effect on the HPA axis and as a trigger of MCS, although greater sinusoid dilatation was found in the anterior pituitary gland at higher concentrations of formaldehyde.