Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

Citation
A. Lof et al., Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats, PHARM TOX, 85(2), 1999, pp. 92-97
Citations number
30
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGY & TOXICOLOGY
ISSN journal
09019928 → ACNP
Volume
85
Issue
2
Year of publication
1999
Pages
92 - 97
Database
ISI
SICI code
0901-9928(199908)85:2<92:DODWSI>2.0.ZU;2-8
Abstract
Petroleum products with low content of aromatics have been increasingly use d during the past years. This study investigates tissue disposition of dear omatised white spirit. In addition, brain neurotransmitter concentrations w ere measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg/l), o r 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/wee k up to 3 weeks. Five rats from each group were sacrificed immediately afte r the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total whi te spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and tot al white spirit in blood and brain were not affected by the duration of exp osure. Two hours after the end of exposure the n-decane concentration decre ased to about 25% in blood and 50% in brain. A similar pattern of eliminati on was also observed for n-nonane, n-undecane and total white spirit in blo od and brain. In fat tissue the concentrations of n-nonane, n-decane, n-und ecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After th e 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-u ndecane, and total white spirit decreased very slowly compared with the rat e of decrease in blood and brain suggesting that long-lasting redistributio n from fat to brain may occur. One week of exposure at 800 p.p.m. caused a statistically significant increase in whole brain dopamine concentration wh ile the noradrenaline concentration was unaffected. Exposure at both exposu re levels for 1 week caused a statistically significantly decreased concent ration of 5-hydroxytryptamine in whole brain. The reduction was related to the exposure concentration. These changes in neurotransmitter concentration s were normalised after 2 and 3 weeks' exposure. In conclusion, after 3 wee ks of exposure the fat:brain:blood concentration coefficients for total whi te spirit were approximately 250:3:1, and redistribution from fat to brain is possible. As total white spirit behaved similarly to the n-alkanes in bl ood, brain, and fat tissue, we suggest that the non-n-alkane white spirit c omponents possess toxicokinetic properties similar to the n-alkanes.