Neurotoxic changes in rats exposed to the fragrance compound acetyl ethyl tetramethyl tetralin.
Spencer-PS; Sterman-AB; Horoupian-D; Bischoff-M
Neurotoxicology 1979 Jan; 1(1):221-237
The behavioral and neuropathological changes occurring in rats exposed to acetyl-ethyl-tetramethyl-tetralin (88299) (AETT) were assessed. A total of 32 male and female Sprague-Dawley-rats was exposed to AETT for periods of up to 26 weeks by oral and topical routes. Topical administration of the agent utilized daily doses of 9, 18, or 36mg/kg body weight for periods of 8 or 26 weeks or daily doses of 50 or 100mg/kg for 11 weeks. Rats treated orally were given either 25mg/kg or 50mg/kg AETT daily for a period of between 12 and 26 weeks. The exposed animals were compared to age matched vehicle controls. The rats were observed for clinical behavioral signs, and neurohistological examination was performed upon sacrifice at completion of the exposure period. The exposed rats showed diminished weight gain, a blue discoloration of the skin and eyes, and neurological and behavioral signs as a function of dose and time. Animals dosed at levels greater than 18mg/kg AETT per day were hyperirritable, had abnormal habituation to auditory and tactile stimuli, and showed excessive spontaneous motor activity and gait abnormalities. Dosage groups greater than 25mg/kg per day were characterized by an intermittent back arching syndrome at 3 to 4 weeks with an abnormal hind limb extensor reflex by 5 weeks. The discoloration and clinical signs were concomitant with structural damage throughout the central and peripheral nervous systems including the accumulation of abnormal lipopigment granules in the neurons and myelinating cells, symmetrical demyelination, and scattered neuron cell body and nerve fiber degeneration. The authors conclude that the oral and percutaneous administration of AETT has cumulative neurotoxic effects in rats.
NIOSH-Publication; NIOSH-Grant; Grants-other; Laboratory-animals; Skin-absorption; Peripheral-nervous-system; Toxic-effects; Neuropathology; Cosmetics-industry
Pathology Albert Einstein Coll of Med 1300 Morris Park Avenue Bronx, N Y 10461
Other Occupational Concerns; Grants-other
Yeshiva University, New York, New York