Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats.
Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg/1), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after 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 white 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 total white spirit in blood and brain were not affected by the duration of exposure. Two hours after the end of exposure the n-decane concentration decreased to about 25% in blood and 50% in brain. A similar pattern of elimination was also observed for n-nonane, n-undecane and total white spirit in blood and brain. In fat tissue the concentrations of n-nonane, n-decane, n-undecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After the 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-undecane, and total white spirit decreased very slowly compared with the rate of decrease in blood and brain suggesting that long-lasting redistribution 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 while the noradrenaline concentration was unaffected. Exposure at both exposure levels for 1 week caused a statistically significantly decreased concentration of 5-hydroxytryptamine in whole brain. The reduction was related to the exposure concentration. These changes in neurotransmitter concentrations were normalised after 2 and 3 weeks' exposure. In conclusion, after 3 weeks of exposure the fat:brain:blood concentration coefficients for total white 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 blood, brain, and fat tissue, we suggest that the non-n-alkane white spirit components possess toxicokinetic properties similar to the n-alkanes.
Löf
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Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.
Lam
H R
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Gullstrand
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Ostergaard
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G
Ladefoged
O
O
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D006207:Half-Life; D006838:Hydrocarbons / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D007509:Irritants / Q000633:toxicity; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000493:pharmacokinetics* / Q000633:toxicity
D001679:Biogenic Amines; D006838:Hydrocarbons; D007509:Irritants; D012997:Solvents; C013089:ligroin