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EC number: 941-496-7
CAS number: 1689576-89-3
This study describes a 5-day inhalation exposure (days 0–4) of BN rats
to two concentration x exposure time (C×t) relationships of 1000, 5000,
and 10,000 mg MDI/m3 ×min at exposure durations of either 10 or 360 min.
This was followed by four 30 min inhalation challenges to 40 mg MDI/m3
on target days 20, 25, 50, and 65. After the last challenge, changes in
breathing patterns delayed in onset were recorded and allergic lung
inflammation was probed by bronchoalveolar lavage (BAL). In a subsequent
study groups of rats were sensitized using the 10 min C×t protocol and
challenged 3 times at 40 mg MDI/m3. At the fourth challenge a dose
escalation regimen was used to determine the elicitation threshold on
‘asthmatic’ rats. The most sensitive endpoints characterizing an
allergic pulmonary inflammation were BAL-neutrophils and physiological
measurements showing respiratory changes delayed in onset. The dose
escalation challenge yielded an elicitation threshold (NOAEL) of 5 mg
MDI-aerosol/m3 at 30 min challenge duration.
In summary, the results suggest the C×t product of MDI-aerosol that
triggers an elicitation response in ‘asthmatic’ rats is slightly below
of that causing acute pulmonary irritation in naïve rats. The high
concentration delivered to the respiratory tract during the10 min
exposure period elicited a more vigorous response than the similar C×t
at 360 min. Therefore, short high level exposure patterns appear to bear
a higher sensitizing potency than equal C×t products at longer exposure
periods. Taking into account the respective differences in exposure
intensities, the comparison of elicitation thresholds of BN rats
sensitized by inhalation exposure did not demonstrate essential
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