SHORT-TERM AND SUBCHRONIC REPEATED EXPOSURE STUDIES WITH 5-ETHYLIDENE-2-NORBORNENE VAPOR IN THE RAT

5-Ethylidene-2-norbomene (ENB) is an industrial chemical whose physica l properties indicate a likelihood for vapor exposure to humans, The p otential for target organ or cumulative toxicity was investigated in r ats exposed for 6h per day for 9 days over an 11-day period, or 66 or 67 days over 14 weeks; 4-week recovery animals were added to the 14-we ek study, iMean analytically measured ENB vapor concentrations (+/-SD) were 52 +/- 1.5, 148 +/- 2.3 and 359 +/- 4.2ppm for the 9-day study a nd 4.9+/-0.14, 24.8 +/- 1.23 and 149 +/- 4.40 ppm for the subchronic s tudy. There were no mortalities, and clinical signs were limited to pe riocular swelling and/or encrustation, and urogenital area wetness, Bo dy weight gain was decreased in the 9-day 359 ppm females and in the s ubchronic 24.8 and 149 ppm males, A minimal macrocytic anemia was pres ent in subchronically exposed males, which resolved during the recover y period, In the 9-day study increased liver weight was associated wit h minimal centrilobular hepatocytomegaly and cytoplasmic basophilia wi th no degenerative or serum biochemical liver function changes, sugges ting an adaptive response, Only relative liver weights were increased in the subchronic 149 ppm males, and no histopathological findings wer e observed, Principal target organ effects were to the thyroid gland, which showed an exposure concentration-related, but not exposure time- related, depletion of follicular colloid that resolved during the reco very period, together with light microscopic evidence for a hypertroph ic and hyperplastic response in the follicular epithelium that resolve d more slowly, The thyroid colloid depletion was a graded effect witho ut a clear no-effect concentration, but was not accompanied by any cli nical or clear biochemical evidence for thyroid dysfunction, A no-effe ct concentration of 4.9 ppm was established for the follicular cytolog ical effects. (C) 1997 John Wiley & Sons, Ltd.