Evaluating the validity and applicable domain of the toxic load model: Impact of concentration vs. time profile on inhalation lethality of hydrogen cyanide

The ten Berge model (or ‘‘toxic load’’ model) is often used to estimate the acute toxicity for varying combinations of inhaled concentration and duration. Expressed as Cn X t = toxic load (TL), TLs are assumed constant for various combinations of concentration (C) and time (t). Experimental data in a recent acute inhalation study of rats exposed to time-varying concentrations of hydrogen cyanide (HCN) supported the validity of the toxic load model except under very brief, discontinuous, high concentration exposures. In the present investigation, experiments were conducted to extend the evaluation of the applicable domain of the model for acute lethality of HCN in the rat (cumulative exposure range of 2900–11,000 ppm min). The lethality of HCN over very short (\u3c5 min) durations of high concentrations did not conform to the toxic load model. A value of n = 1.57 was determined for uninterrupted exposures P5 min. For 30-min exposures, the presence or absence of a gap between two exposure pulses of different concentrations, the relative duration, relative height, and the ordering of the pulses (low then high, vs. high then low) did not appear to have a meaningful impact on the toxic load required for median lethality

Changes in motor behavior and lumbar motoneuron morphology following repeated chlorpyrifos exposure in rats.

Chlorpyrifos is an organophosphate pesticide associated with numerous health effects including motor performance decrements. While many studies have focused on the health effects following acute chlorpyrifos poisonings, almost no studies have examined the effects on motoneurons following occupational-like exposures. The main objective of this study was to examine the broad effects of repeated occupational-like chlorpyrifos exposures on spinal motoneuron soma size relative to motor activity. To execute our objective, adult rats were exposed to chlorpyrifos via oral gavage once a day, five days a week for two weeks. Chlorpyrifos exposure effects were assessed either three days or two months following the last exposure. Three days following the last repeated chlorpyrifos exposure, there were transient effects in open-field motor activity and plasma cholinesterase activity levels. Two months following the chlorpyrifos exposures, there were delayed effects in sensorimotor gating, pro-inflammatory cytokines and spinal lumbar motoneuron soma morphology. Overall, these results offer support that subacute repeated occupational-like chlorpyrifos exposures have both short-term and longer-term effects in motor activity, inflammation, and central nervous system mechanisms

Indications of Endocrine Disruptor Effects of JP-5 Jet Fuel Using a Rat-Model Reproductive Study and an In Vitro Human Hormone Receptor Assay

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with ingested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant referred to as HydroRenewable Jet (HRJ) fuel, to help evaluate potential effects of ingested jet fuel. The results of the in vivo study provide evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated that JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while HRJ was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid receptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action