ARCHIVED - A Summary of the Health Hazard Assessment of Morpholine in Wax Coatings of Apples

Morpholine is a solvent and emulsifier used in the preparation of wax coatings for fruits and vegetables. In the presence of excess nitrite, formed mainly from naturally-occurring nitrate in the diet, morpholine can be chemically modified (nitrosated) to form N-nitrosomorpholine (NMOR), a genotoxic carcinogen in rodents. While morpholine alone does not appear to pose a health concern, the main issue is whether sufficient NMOR can be produced by humans upon ingestion, to pose a health risk.

Morpholine itself is neither a carcinogen nor a teratogen and does not cause chronic toxicity in rats and mice. Based on a no observed adverse effect level (NOAEL) in a chronic oral toxicity study and several safety factors, an acceptable daily intake (ADI) of 0.48 mg/kg bw/day was estimated. When not considering the potential for nitrosation, the respective morpholine exposure for children and adults is about 8% and 5% of the ADI, and not a cause for concern.

In studies conducted in experimental animals it has been determined that the formation of NMOR is dependent on the administration of sufficiently large doses of morpholine and nitrite. Under these specific conditions, rats fed morpholine and nitrite develop hepatocellular carcinoma (cancer of the liver), presumably due to the formation of NMOR. Although it is often assumed that there is some probability of harm at any level of exposure to a genotoxic carcinogen, actual exposure may be so low that the health risk is essentially negligible. Extrapolation of rat tumour data was used to estimate a safe dose in humans (4.3 ng/kg bw/day).

Regarding the presence of NMOR on apples coated with wax containing morpholine:

• No NMOR was determined to be present on these apples, and no NMOR was formed when morpholine and nitrite were combined in experiments conducted in the presence of apple flesh.
• The possibility that morpholine might be nitrosated by humans to form NMOR during digestion was investigated. Since there is no direct human data on the nitrosation rate of morpholine to NMOR, this was estimated indirectly.
• The inhibitory effects of antioxidants present in apple were also considered.
• From the estimated morpholine exposure, the possible endogenously formed NMOR was estimated to be 2.2 and 3.6 ng/kg bw/day for adults and children, respectively. This possible exposure to NMOR derived from morpholine on waxed apples is less than the above estimated safe dose of 4.3 ng/kg bw/day.
• Uncertainties in this estimate of NMOR formation include the physiological differences between humans and rats, and actual levels of nitrite consumed. It is unlikely that these uncertainties would increase the estimated NMOR formation.

It was concluded that morpholine, as currently used in the wax coating of fruits and vegetables, does not pose a risk to health.