Warfarin

CAS number: 81-81-2

NIOSH REL: 0.1 mg/m3 TWA

Current OSHA PEL: 0.1 mg/m3 TWA

1989 OSHA PEL: Same as current PEL

1993-1994 ACGIH TLV: 0.1 mg/m3 TWA

Description of substance: Colorless, odorless, crystalline powder.

LEL :. . Unknown

Original (SCP) IDLH*: 350 mg/m3 [*Note: "Effective" IDLH = 200 mg/m3 -- see discussion below.]

Basis for original (SCP) IDLH: No data on acute inhalation toxicity are available on which to base the IDLH for warfarin. The IDLH of 350 mg/m3, therefore, is estimated from the rat oral lethal dose of 50 mg/kg [Sax 1975]. Because of the assigned protection factor afforded by each device, however, 2,000 ´ the OSHA PEL of 0.1 mg/m3 (i.e., 200 mg/m3) is the concentration above which only the "most protective" respirators are permitted. The chosen IDLH is probably conservative, because the rat is particularly susceptible to warfarin, and single doses are not usually as harmful as small, repeated doses.

Short-term exposure guidelines: None developed

ACUTE TOXICITY DATA:

Lethal dose data:

Species	Reference	Route	LD50 (mg/kg)	LDLo (mg/kg)	Adjusted LD	Derived value
Mouse Dog Cat Rat Rat	Coumafene 1989 Coumafene 1989 Coumafene 1989 Hayes 1967 Sax 1975	oral oral oral oral oral	3 3 6 1.6 -----	----- ----- ----- ----- 50	21 mg/m3 21 mg/m3 42 mg/m3 11 mg/m3 350 mg/m3	2.1 mg/m3 2.1 mg/m3 4.2 mg/m3 1.1 mg/m3 35 mg/m3

Human data: The sodium salt of warfarin has been used as an anticoagulant drug with a loading dose of 30 to 60 mg [ACGIH 1991] [Note: This is equivalent to a worker being exposed to 20 to 40 mg/m3 for 30 minutes, assuming a breathing rate of 50 liters per minute and 100% absorption.]. It has been reported that 6.667 mg/kg is the lethal oral dose [Yakkyoku 1977] [Note: This is equivalent to a worker being exposed to about 300 mg/m3 for 30 minutes, assuming a breathing rate of 50 liters per minute and 100% absorption.].

Revised IDLH: 100 mg/m3 Basis for revised IDLH: No inhalation toxicity data are available on which to base an IDLH for warfarin. Therefore, the revised IDLH for warfarin is 100 mg/m3 based on acute toxicity data in humans [Yakkyoku 1977]. This may be a conservative value due to the lack of acute inhalation toxicity data for workers.

REFERENCES:

1. ACGIH [1991]. Warfarin. In: Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, p. 633.

2. Coumafene [1989]. Defensi des Vegetaux 43(255-256):20 (in French).

3. Hayes WJ Jr [1967]. The 90-dose LD50 and a chronicity factor as measures of toxicity. Toxicol Appl Pharmacol 11:327-335.

4. Sax NI [1975]. Dangerous properties of industrial materials. 4th ed. New York, NY: Van Nostrand Reinhold Company, Inc., p. 1241.

5. Yakkyoku (Pharmacy) [1977]; 28:329 (in Japanese).