Registration of a Product containing the New Active Ingredients, Nitrogen dioxide and 

Dinitrogen tetroxide 

Regulatory Action: 

EPA has granted an unconditional registration ofNoxilizer N02 Sterilant, an end use product, 

containing the new active ingredients, dinitrogen tetroxide and nitrogen dioxide (N02). 

Noxilizer, Incorporated requested this action under PRIA as an A420. Nitrogen dioxide and 

dinitrogen tetroxide exist in equilibrium in commerce. Once the formulation is exposed to heat 

during sterilization, the equilibrium shifts, and dinitrogen tetroxide is converted to nitrogen 

dioxide. 

Noxilizer N02 Sterilant is a gaseous sterilant for use in industrial, commercial and institutional 

settings on laboratory equipment, isolators, medical devices, pharmaceuticals, and 

pharmaceutical equipment. Noxilizer N02 Sterilant is not labeled for use in sterile reprocessing 

of reusable medical devices. 

Human Health Risk Assessment: 

Two exposure scenarios were assessed for sterilization workers who may inhale N02 in an 

occupational setting: I) peak (one hour) exposures to N02 during opening of sterilization 

chamber doors or isolation units after treatment; and 2) average dai ly (eight hour time 

weighted average) exposure to N02 potentially released into the room air resulting from 

multiple cycles of treatments and opening of sterili zation chamber door·(s) and isolation units 

during a single day. 

The levels of concern (LOCs) are I 00 ppb for one hour time weighted average (TWA) 

exposures and 34 ppb for eight hour TWAs. These LOCs are based on epidemiology studies 

and are applicable to short, intennediate and long te1m exposures. Risk findings from the 

proposed use are presented below: 

(1) Sterilization worker inhalation exposures to N02 from opening of the isolator or 

sterilization chamber door·(s) are not likely to be a risk of concern. The maximum 

measured concentration during the period of highest exposure (i .e. door opening) was 177 

ppb for the isolator and !58 ppb for the sterilization chamber. Although these va lues are 

above the acute endpoint value of 100 ppb, they represent ma;-cimum exposures occurring 

over a span of only a few minutes from opening of the isolator or sterilization chamber 

doors. By comparison, the endpoint value of I 00 ppb represents a one hour TWA. In 

light of the fact that exposure from opening of isolator or sterilization chamber doors 

occurs for only a few minutes after each steri li zation cycle of90 minutes, the average 

exposure over any one hour period would not likely exceed I 00 ppb. 

(2) Average Daily Exposure. Sterilization worker 8 hour TWA exposures for the isolator unit 

is 29 ppb, which is below EPA's LOC of34 ppb based on room ventilation requirements 

on the product labeling (five air changes per hour). Sterilization worker 8 hour TWA 
exposures for the sterili zation chamber is 23 ppb, which is less than LOC of 34 ppb and is 

not of concern. 

Ecological Risk Assessment: 

The use pattern ofNoxilizer N02 Steril ant will not result in any additional exposure to N02 in the 

environment because the sterilant will be contained in the sterilization equipment. In addition, air 

scrubbers are required to be used as a safety measure to remove N02 during the discharge 

process which will preclude accidental release to the environment and exposure to non-target 

organisms. Therefore, N02 exposure from the use of this product should not cause any adverse 

effects to non-target organisms. All aquatic, avian, and terrestrial plant ecological effects studies 

have been waived. 

Efficacy Assessment: 

The submitted efficacy data demonstrated that Noxilizer N0 2 Steril ant is an effective sterilant by 

showing a 100% kill of Bacillus subtilis and Clostridium sporogenes when used according to the 

proposed product label. 

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