3M Company 1995.

100,000 ppm for 4 h: no deaths.

End point/Concentration/Rationale: Severe clinical signs/89,300 ppm/considered lethal threshold due to severity of signs. Supported by no deaths in rats at 100,000 ppm (3M Company 1995).

Uncertainty Factors/Rationale:

Total uncertainty factor: 3

Interspecies: 1—respiratory rate and cardiac output higher in beagles and rats than in humans.

Intraspecies: 3—no significant toxicological end points identified in other studies; poor solubility in biological fluids for all species.

Modifying Factor: 2—limited data on humans; limited number of animals in several studies.

Animal to Human Dosimetric Adjustment: Not applied.

Time Scaling: Not applied; low solubility of test compound in blood, rapidly reaches equilibrium; cardiac response does not change when chemical is administered for hours.

Data Adequacy: Well conducted repeat dose, subchronic, developmental/reproductive, neurotoxicity, and cardiac sensitization studies. Limited human studies; limited number of animals in this and several support studies. The 89,300 ppm may be a conservative estimate of a lethal concentration as no rats died after a 4-h exposure to 100,000 ppm.



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