PROPYLENE GLYCOL DINITRATE

OSHA comments from the January 19, 1989 Final Rule on Air Contaminants Project extracted from 54FR2332 et. seq. This rule was remanded by the U.S. Circuit Court of Appeals and the limits are not currently in force.

CAS: 6423-43-4; Chemical Formula: C₃H₆N₂O₆

OSHA previously had no exposure limit for propylene glycol dinitrate. The ACGIH recommends a TLV-TWA of 0.05 ppm, with a skin notation. The Agency proposed a permissible exposure limit of 0.05 ppm TWA, with a skin notation, for this substance, and NIOSH (Ex. 8-47, Table N1) concurred with the proposed limit. The final rule establishes a PEL of 0.05 ppm but does not include the proposed skin notation. When freshly prepared, propylene glycol dinitrate is a colorless liquid with a disagreeable odor.

Exposure to this substance affects blood pressure, causes methemoglobinuria and respiratory toxicity, injures liver and kidney tissues, and distorts vision. Propylene glycol dinitrate can also cause headache and incoordination.

The oral LD(50) value for the rat is between 480 and 250 mg/kg (Clark and Litchfield 1969/Ex. 1-543; Andersen and Mehl 1973/Ex. 1-536), and the subcutaneous LD(50) is 530 mg/kg (Andersen and Mehl 1973/Ex. 1-536). Mice are reported to be somewhat more resistant, with a subcutaneous LD(50) of slightly more than 1200 mg/kg; however, cats appear to be even more susceptible to propylene glycol dinitrate and exhibit a subcutaneous LD(50) of between 200 and 300 mg/kg (Clark and Litchfield 1969/Ex. 1-543). In all species studied, death occurs by anoxia, which is caused by almost complete conversion of hemoglobin to methemoglobin (Clark and Litchfield 1969/Ex. 1-543). Skin tests in albino rabbits did not produce irritation, but ocular instillation caused transient conjunctival redness (Jones, Strickland, and Siegel 1972/ Ex. 1-742). Twenty-day skin exposures in rabbits at 1 g/kg caused minor irritation, and at 2 g/kg, rabbits became weak and cyanotic; one of five rabbits died, and this animal’s hemoglobin and hematocrit values had decreased. When the dose was increased to 4 g/kg, the rabbits’ methemoglobin values rose to 34.5 percent at death (Jones, Strickland, and Siegel 1972/ Ex. 1-742). Continuous 90-day inhalation exposures at 10 ppm caused kidney and liver changes in dogs; exposures at 35 ppm caused heavy iron deposits in the liver, spleen, and kidneys. Female (but not male) rats showed a drop in blood pressure within 30 minutes after injection of doses above 5 mg/kg. Rhesus monkeys displayed mydriasis in 90-day exposures at 35 ppm but no change in avoidance behavior during a visual discrimination and acuity threshold test (Jones, Strickland, and Siegel 1972/ Ex. 1-742).

In humans, eight-hour exposures to 0.2 ppm or higher concentrations of propylene glycol dinitrate resulted in visual distortion and headache (Stewart, Peterson, Newton et al. 1974, as cited in ACGIH 1986/Ex. 1-3, p. 502). Although subjects developed a tolerance for the headache response, the visual effects were cumulative. Impaired balance occurred after 6.5 hours of exposure to 0.5 ppm, and a 40-minute exposure to 1.5 ppm caused eye irritation. Subjects exposed at 0.5 ppm for 8 hours experienced a consistent elevation in diastolic pressure but no pulmonary irritation. At concentrations of 0.03 to 1.5 ppm, no hematologic effects were observed (Stewart, Peterson, Newton et al. 1974, as cited in ACGIH 1986/Ex. 1-3, p. 502). Studies of human exposures to levels below 0.1 ppm do not report chronic neurotoxicity (Horvath, Ilka, Boyd, and Markhan 1981/Ex. 1-557).

The skin notation included in the proposal for this substance is not included in the final rule because evidence demonstrates that the dermal LD(50) in rabbits is even greater than 2 g/kg (see the discussion in Section VI.C.18 for OSHA’s policy on skin notations). No comments except those from NIOSH were received on the health effects of propylene glycol dinitrate.

OSHA is establishing an 8-hour TWA limit of 0.05 ppm for propylene glycol dinitrate. The Agency concludes that this limit will protect workers against the significant risks of hepatotoxic, hematologic, and central nervous system effects (all of which constitute material health impairments) that exist from workplace exposure at the levels permitted in the absence of any OSHA PEL.