Repeated Exposure of Rats to Jp-4 Vapor Induces Changes in Neurobehavioral Capacity and 5-Ht/5-Hiaa Levels

Abstract

Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or 60-d recovery period, rats completed a battery of 8 tests selected from the Navy Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Exposure to JP-4 vapor resulted in significant changes in neurobehavioral capacity on several tests that varied as a function of the duration of the recovery period. Rats were evaluated for major neurotransmitter and metabolite levels in five brain regions and in the blood serum. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be significantly elevated in several brain regions as well as in the blood serum in the vapor-exposed groups. Results of the rat study are compared to previously reported neurobehavioral evaluations of European manufacturing personnel exposed chronically to jet fuel vapor.

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

“…To date, no human studies have reported differences in water intake between fuel-exposed and nonexposed subjects. Nordholm et al (1999), exposed male Sprague-Dawley rats to JP-4 vapor (2000 mg/m 3 ) for 6 h/d for 14 consecutive days, then measured changes in performance capacity using tests selected from the Neurobehavioral Toxicity Assessment Battery (NTAB) (Ritchie et al, 1995). The authors reported significantly increased approach to an appetitive stimulus (raw hamburger meat), significantly reduced prepulse inhibition of the acoustic startle response, significantly decreased mean time to tail flick nociceptive responses, and significantl y decreased spontaneous, horizontal locomotor activity in JP-4 exposed rats, as compared to controls.…”

“…These changes typically involve acute or persisting modulation of CNS DA, 5-HT, and/or NA neurotransmitter systems and/or of the hypothalamo-pituitary axis, and may be accompanied by subtle changes in neurobehavioral capacity. Recently published research (Nordholm, 1998;Witzmann et al, 1999;Nordholm et al, 1999; indicate that repeated exposure of rats to human "real-world" concentrations of JP-4, JP-5, or JP-8 jet fuel vapor induce persisting changes in protein expression, CNS neurotransmitters levels, and neurobehavioral capacity in rats. While observational analysis of chronically exposed animals may indicate no apparent deficits, use of appropriate neurobehavioral tests may reveal significant changes in sensory, motivational, fine motor, and higher cognitive capacity.…”

“…Additionally, there would appear to be increasing evidence that exposure to hydrocarbon fuel aerosol may be significantly more damaging than similar exposures to vapor consequences (Harris et al, 1997a;Harris, 1998;Witten, 1992Witten, , 1993. From animal studies, it has been hypothesized that hydrocarbon fuel exposures may induce some form of CNS general sensitization, kindling, or time-dependent sensitization, possibly associated with a neurotransmitter imbalance in at least the DA or 5-HT systems (Nordholm, 1998;Nordholm et al, 1999). The following sections contain a summary review of CNS consequences from exposure of humans or laboratory animals to hydrocarbon fuels.…”

“…Again, this observation of altered ingestion and motor activity should be considered in evaluating hydrocarbon fuel-induced changes in operant performance. Nordholm et al (1999), while exposing SpragueDawley rats to JP-4 vapor (2000 mg/m 3 ) for 6 h/d for 14 consecutive days, reported a significantly increased approach to a "novel" appetitive stimulus (raw hamburger meat) measured more than 3 wk postexposure. Again, increased appetitive approach, hypothesized by the authors to result from fuel-induced sensitization of dopaminergic systems, may be manifested as increased learning of food-reinforced tasks.…”

Comparative electrophysiological evaluation of hippocampal function following repeated inhalation exposures to JP-8, Jet A, JP-5, and the synthetic Fischer Tropsch fuel

“…Early studies indicated that exposures to JP-5, JP-8, or FT produced inflammatory effects on the immune system (Nordholm 1999;Mattie et al 2011). Thus, plasma levels of inflammatory cytokines were determined to assess influence of jet fuel on inflammation.…”