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

Hyperbaric Oxygen in the Prevention of Carbon Monoxide Induced Delayed Neurological Sequelae in Male Sprague Dawley Rats (Rattus norvegicus)

In Carbon Monoxide (CO) induced Delayed Neurological Sequelae (DNS) clinical signs develop 1 to 6 weeks after CO has cleared the body. The aim of this experiment was to develop a model of CO induced DNS which closely mimics real world conditions both in exposure and treatment. The model was challenged with hyperbaric or normobaric oxygen, or room air. Basic behaviors were measured by Open Field test on days 1, 7, 14 post exposure and treatment. No significant difference in behavior was observed between exposed and control animals or between treatment groups. Histological analyses showed no DNA or necrotic damage to the basal ganglia, cortex, or hippocampus in CO exposed animals at time of euthanasia regardless of treatment. Data suggest variability in tolerance to CO and development of DNS. Data also indicates that the in vivo COHb half-life is not constant across species

Hyperbaric Oxygen in the Prevention of Carbon Monoxide Induced Delayed Neurological Sequelae in Male Sprague Dawley Rats (Rattus norvegicus)

In Carbon Monoxide (CO) induced Delayed Neurological Sequelae (DNS) clinical signs develop 1 to 6 weeks after CO has cleared the body. The aim of this experiment was to develop a model of CO induced DNS which closely mimics real world conditions both in exposure and treatment. The model was challenged with hyperbaric or normobaric oxygen, or room air. Basic behaviors were measured by Open Field test on days 1, 7, 14 post exposure and treatment. No significant difference in behavior was observed between exposed and control animals or between treatment groups. Histological analyses showed no DNA or necrotic damage to the basal ganglia, cortex, or hippocampus in CO exposed animals at time of euthanasia regardless of treatment. Data suggest variability in tolerance to CO and development of DNS. Data also indicates that the in vivo COHb half-life is not constant across species