APPENDIX II-AS: Gupta, et al, Effect of pyrethroid-based liquid mosquito repellent inhalation on the blood-brain barrier function and oxidative damage in selected organs of developing rats, Journal of Applied Toxicology, Volume 19, Issue 1 , Pages 67 - 72


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Volume 19, Issue 1 , Pages 67 - 72

Published Online: 14 Apr 1999

Copyright 1999 John Wiley & Sons, Ltd.

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 Research Article

Effect of pyrethroid-based liquid mosquito repellent inhalation on the blood-brain barrier function and oxidative damage in selected organs of developing rats

Alka Gupta 1, Darshika Nigam 1, Amita Gupta 1, G. S. Shukla 2, A. K. Agarwal 1 *

1Predictive Toxicology Research Group, Industrial Toxicology Research Centre, Lucknow-226001, India
2Department of Biochemistry, C-440 Given Medical Building, College of Medicine, University of Vermont, Burlington, VT 05405, USA

*Correspondence to A. K. Agarwal, Industrial Toxicology Research Centre, P.O. Box-80, M. G. Marg, Lucknow-226001 (U.P.), India. ITRC Communication no. 1994

Funded by:
 CSIR (Council of Scientific and Industrial Research)



pyrethroid; mosquito repellent; BBB; oxdative damage; organs; development




Pesticides have been implicated in various neurological disorders in humans and experimental animals. Our earlier studies have demonstrated a high vulnerability of developing blood-brain barrier (BBB) towards very low level exposure of quinalphos, cypermethrin and lindane. Earlier it has been observed that a cypermethrin-induced increase in the BBB permeability of neonatal rats was found to be persistent, requiring a longer period of withdrawal for complete recovery. These observations lead us to investigate the effect of a commonly available liquid mosquito repellent (MR) containing a pyrethroid compound, allethrin (3.6% w/v), on the functional integrity of the developing BBB and on certain parameters of oxidative damage in brain, liver and kidney. Two-day-old rat pups were allowed to inhale the MR (18 h per day) for 8 days (postnatal days (PND) 2-9). Rats exposed to MR were further withdrawn from the exposure for 8 days (PND 10-17) to study whether the changes induced following inhalation are reversible. Results of the study have shown a significant increase in the BBB permeability (45%) of the MR-exposed rat pups to a micromolecular tracer, sodium fluorescein (mol. wt. 376), used for the quantitative assessment of the BBB permeability, suggesting a delayed maturity of the BBB system. Brain glutathione (GSH) levels were also decreased (17%) in the exposed individuals. The oxidatively damaged end-products of lipids, measured as lipid hydroperoxides and conjugated dienes, were found to be increased in brain (42%, 16%), liver (34%, 20%) and kidney (68%, 29%), respectively. The oxidative product of protein, measured as protein carbonyls, was also increased significantly in liver (43%) and kidney (16%) of the MR-exposed rat pups as compared to age-matched controls. The biochemical changes that occurred in the BBB permeability and the oxidatively damaged end-products following MR inhalation in neonatal rats were, however, found to be completely recovered except for an increase in brain GSH (28%) level. The results suggest the possibility of health risk due to exposure to pesticide-based mosquito repellents, especially when exposure takes place in individuals at an early age. Copyright 1998 John Wiley & Sons, Ltd.

Received: 7 April 1998; Revised: 25 August 1998; Accepted: 18 September 1998