Neonatal exposure to toluene: effects on the development of liver microsomal cytochrome P-450 and serum hormone levels in the rat.
Lactating Sprague-Dawley rats and their pups were exposed on postnatal days 1-7, 6 h/day, to 80, 500 and 1000 ppm toluene, respectively, by inhalation. Exposure to 80 ppm toluene decreased the liver microsomal AHH activity and the rate of 7 alpha- and 6 beta-hydroxylation of androstenedione in 8-day-old-pups. On the other hand, neonatal exposure to 500 or 1000 ppm toluene resulted in a significant increase in AHH and 7-ethoxyresorufin O-deethylase activities and in the formation of 16-oxygenated metabolites of androstenedione in 8-day-old animals. Exposure to toluene increased the cytochrome P-450 content at all 3 dose levels in male but not in female pups. Twenty-one days after neonatal exposure no such effects were seen in young animals of either sex. In 56-day-old male rats, however, neonatal exposure to 80 ppm toluene resulted in a decreased rate of 6 beta-hydroxylation of androstenedione and a reduced AHH activity. No such effects were seen in female rats of the same age. Neonatal exposure to toluene affected the body and liver weights in 8-day-old pups of both sexes but had no effect on these parameters in 21-day-old animals of either sex. Exposure to 80 ppm toluene during the neonatal period gave a significantly increased body weight of 56-day-old male but not of female rats of the same age although this treatment increased liver weight in both sexes at this age. Serum testosterone levels were decreased in 21-day-old male rats following neonatal exposure to 80 or 500 ppm toluene and in 56-day-old male rats exposed neonatally to 1000 ppm toluene. In conclusion, exposure to toluene during the first week of life caused significant changes in various liver microsomal cytochrome P-450 dependent enzyme activities in 8-day-old pups, whereas the long-term effects on liver metabolism of the adult animal were small.
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001273:Atmosphere Exposure Chambers; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects*; D004958:Estradiol / Q000097:blood; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014050:Toluene / Q000633:toxicity*
D014050:Toluene; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1