The sub-chronic oral toxicity of 1,3,5-trimethylbenzene in Sprague-Dawley rats.
The systemic toxicity of a trimethylbenzene isomer and constituent of C9 aromatic solvents (1,3,5-trimethylbenzene, 135-TMB) was studied in Sprague-Dawley rats following a 90-day oral gavage exposure to 0, 50, 200 and 600 mg/kg/day. No statistically significant effects on body weight, body weight gain or food consumption were observed at study termination. Treatment-related changes in clinical chemistry parameters at the end of the 90-day dosing period were limited to small, but statistically significant, increases in phosphorus levels in high dose males and females. Liver enlargement in high dose male/female rats was considered an adaptive response as this was reversible and was not associated with histopathological lesions or increased liver enzyme markers indicative of liver damage. Kidney weight changes were limited to a small, but statistically significant, increase in relative weights in high dose males. This was not associated with histopathological lesions and thus not considered toxicologically relevant. Overall, the No-Observed-Adverse-Effect-Level (NOAEL) was the highest concentration tested (600 mg/kg/day). The results of the present study are relevant for assessing the risk of trimethylbenzenes through the oral route of exposure and provide a basis for the development of provisional screening values for trimethylbenzene isomers while avoiding the uncertainty associated with route-to-route extrapolation.
ExxonMobil Biomedical Sciences, Inc., 1545 Route 22 E., Annandale, NJ 08801, USA. Electronic address: moyinoluwa.d.adenuga@exxonmobil.com.
David
D
Adenuga
Shell Health, Shell International B.V., P.O. Box 162, 2501 AN The Hague, The Netherlands.
Juan-Carlos
JC
Carrillo
ExxonMobil Biomedical Sciences, Inc., 1545 Route 22 E., Annandale, NJ 08801, USA.
Richard H
RH
Mckee
D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests
C482494:1,3,5-trimethylenebenzene; D001555:Benzene Derivatives
C9 aromatics; Hydrocarbon solvent; Liver enlargement; Mesitylene; Occupational exposure limit; Oral toxicity; RfD; Trimethylbenzene