ACUTE TOXICITY OF TOLUENE IN MALE AND FEMALE RATS:A SINGLE ORAL DOSE EXPOSURE 2-WEEK STUDY

Author： Mehta Chander S. Sun Pei Nan Zikarge Astate Mumtaz Moiz Kuhn Janice O.

ISSN： 1091-7659

Source： Toxic Substance Mechanisms, Vol.17, Iss.1, 1998-01, pp. : 43-56

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

The Agency for Toxic Substances and Disease Registry (ATSDR) has identified the oral route as the primary route of exposure, and neurotoxicity as the endpoint of concern, in the priority data needs for toluene. The acute oral neurotoxicity of toluene was investigated in male and female Sprague-Dawley rats. Dose selection was made relative to a benchmark dose (BD). The BD was defined as the maximum nonlethal neurotoxic dose and was examined by range-finding studies. The 3 oral (gavage) doses were 3.0 ml/kg (50% BD), 4.5 ml/kg (75% BD), and 6.0 ml/kg (100% BD). To characterize its neurotoxicity, a functional observational battery (FOB) and spontaneous motor activity (SMA) were measured on d 1 (2-3 h and 4-7 h postexposure times for FOB and SMA, respectively), 7, and 14 following toluene administration. The data indicate that on d 1, when compared with the saline controls, toluene-exposed rats (males at 4.5- and 6.0-ml/kg doses and females at 6.0-ml/kg dose) exhibited significantly ( p <.05) greater="" horizontal="" (hz)="" and="" stereotype="" (st)="" motor="" activities.="" however,="" vertical="" (vt)="" activity="" was="" significantly="" (="" p="">< .01)="" depressed="" in="" both="" sexes="" at="" all="" doses.="" fob="" data="" indicated="" that="" on="" d="" 1,="" toluene-treated="" male="" rats="" exhibited="" dose-dependent="" increases="" in="" abnormal="" gait="" (1/10="" rats="" at="" 3-ml/kg,="" 2/="" 10="" rats="" at="" 4.5-ml/kg,="" and="" 7/10="" rats="" at="" 6-ml/kg="" toluene="" doses).="" abnormal="" gait="" was="" present="" in="" 5/10="" females="" at="" 3="" ml/kg="" and="" 6/10="" females="" at="" both="" 4.5-="" and="" 6-ml/="" kg="" toluene="" doses.="" the="" open-field="" rearing="" scores="" were="" lower="" than="" controls="" in="" all="" toluenetreated="" groups="" on="" d="" 1,="" and="" this="" was="" perhaps="" due="" to="" abnormal="" gait="" manifested="" by="" the="" rats.="" on="" d="" 7,="" toluene-treated="" males="" at="" 3-="" and="" 4.5-ml/kg="" doses="" exhibited="" significantly="" (="" p=""><.05) greater="" hz="" and="" vt="" motor="" activities="" when="" compared="" with="" saline="" controls.="" females="" rats="" showed="" hz="" and="" st="" activities="" very="" similar="" to="" controls,="" but="" there="" was="" a="" significant="" decrease="" (="" p=""><.05) in="" vt="" activity="" in="" all="" toluenetreated="" females="" on="" d="" 7="" compared="" to="" saline="" controls.="" fob="" data="" indicated="" that="" rearing="" scores="" were="" higher="" than="" control="" in="" all="" toluene-treated="" rats;however,="" gait="" was="" normal="" in="" all="" animals="" on="" d="" 7.="" by="" d="" 14,="" there="" were="" no="" significant="" differences,="" except="" vt="" activity="" in="" the="" female="" rats="" was="" still="" significantly="" depressed="" at="" 3-="" and="" 4.5-ml/kg="" doses.="" fob="" results="" on="" d="" 14="" were="" similar="" in="" toluene-treated="" rats="" to="" those="" of="" controls.="" the="" d="" 1="" data="" show="" the="" acute="" immediate="" effects="" after="" administration="" of="" the="" solvent,="" whereas="" postexposure="" d="" 7="" and="" 14="" data="" depicted="" delayed="" or="" persistent="" toxic="" effects="" after="" a="" single="" exposure.="">