4.1 The NOAEL and LOAEL values are based on the
toxicological effect known as cardiac sensitization. Cardiac sensitization
occurs when a chemical causes an increased sensitivity of the heart
to adrenaline, a naturally occurring substance, which may result in
the sudden onset of irregular heart beats and possibly heart attack.
4.2 The test protocol should measure the cardiac
sensitization in a stepwise manner using sufficiently small changes
in concentration, such that the interval between the LOAEL and NOAEL
can be accurately determined.
4.3 The test animals should be exposed to a predetermined
concentration of the halocarbon agent for a 5-min period. At the end
of the 5-min exposure, an external dose of adrenaline (epinephrine)
should be administered. If the animal experiences cardiac sensitization,
an effect should be recorded.
4.4 The following standard protocols for cardiac
sensitization may be used for reference:
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.1 Hardy, C.J., I.J. Sharman and G.C. Clark. 1991.
Assessment of Cardiac Sensitisation Potential in Dogs. Rep. No. CTL/C/
2521. Huntingdon Research Centre, Huntingdon, Cambridgeshire, United
Kingdom.
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.2 Reinhardt, C.F., L.S. Mullen and M.E. Maxfield.
1973. Epinephrine induced cardiac arrhythmia potential of some common
industrial solvents. J. Occup. Med. 15:953-955.
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.3 WIL Research Laboratory Reports. Project Nos.
WIL12248, 12265, 12318. WIL Research Laboratories, Inc. 1992.