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Basic toxicokinetics

The metabolism studies indicate that Azodicarbonamide was absorbed, metabolised and excreted in rats. The acute rat oral, dermal and inhalation studies, together with the repeat dose inhalation study, indicated that despite the absorption, metabolism and excretion of Azodicarbonamide there was no resultant adverse toxicity. Similarly, there was no evidence of skin or eye irritation in rabbits or sensitization potential in Guinea pigs.

Dermal absorption

No data available. No data required.

Discussion on bioaccumulation potential result:

No information is available on the toxicokinetics of azodicarbonamide in humans. Most of the toxicokinetic data available for azodicarbonamide come from animal studies (CICAD 1999- SIAR 2001).

 

Absorption

Absorption of azodicarbonamide has been demonstrated following both a single inhalation exposure of up to 6 h (ca. 34% of dose) and a single oral administration (10–33% of dose) of radiolabelled azodicarbonamide to rats F344. In contrast, approximately 90% of a single intratracheally instilled dose was apparently absorbed. The difference in absorption between inhaled and intratracheally instilled azodicarbonamide could be related to the fact that much of the inhaled azodicarbonamide did not reach the lower respiratory tract. Half an hour after a 6-h nose-only exposure of rats to 25 mg/m3 of a dry aerosol (average mass aerodynamic diameter 3.4 µm), 78% of the calculated total intake was located in the gastrointestinal tract (Mewhinney et al., 1987).

 

Distribution

No data.

 

Metabolism

Azodicarbonamide is readily converted to biurea (1,2-Hydrazinedicarboxamide, CAS 110-21-4), the only breakdown product identified, and it is likely that systemic exposure is principally to this derivative rather than to the parent compound (Mewhinney et al., 1987). Azodicarbonamide readily undergoes reduction in the presence of thiol groups to form the stable compound biurea. Given that thiol groups are also present in many biological molecules, there is the potential for this reaction to take place wherever azodicarbonamide encounters thiol groups in biological systems. This has been demonstrated in an experiment in which radiolabelled azodicarbonamide was added to fresh rat blood (Mewhinney et al., 1987). All radioactivity was in the form of biurea within 5 min when untreated blood was used. Radioactivity associated with azodicarbonamide was detected only in blood to which 5 mg unlabelled azodicarbonamide/ml blood was added. This level is very much greater than the levels that humans are likely to encounter.

This metabolism is confirmed by an other study: after repeated inhalation of ADCA for 13weeks in rats no ADCA was found in kidney or lungs or bronchi, but biurea was found in lungs and bronchi (Medinsky et al., 1990)

 

Excretion

Following exposure by both inhalation and oral routes, substantial quantities of the substance remain unabsorbed from the gastrointestinal tract and are passed out in the faeces. Elimination of absorbed azodicarbonamide/biurea is rapid, occurring predominantly via the urine (99% within 72h), and there is very little systemic retention of biurea (Mewhinney et al., 1987).

 

After oral administration of suspension of radiolabelled azodicarbonamide in water or corn oil, less than 10% of the ADA:water or ADA:corn oil dose was excreted in urine, with virtually all of the dose being excreted in faeces by 24h after administration (IRDC 1982, cited in Mewhinney et al., 1987).

 

Conclusion

The previous metabolism studies indicate that Azodicarbonamide was absorbed, metabolised and excreted in rats.  The acute rat oral, dermal and inhalation studies, together with the repeat dose inhalation study, indicated that despite the absorption, metabolism and excretion of Azodicarbonamide there was no resultant adverse toxicity.  Similarly, there was no evidence of skin or eye irritation in rabbits or sensitization potential in Guinea pigs.

References

Mewhinney J.A., Ayres P.H., Bechtold W.E. et al. 1987. The fate of inhaled azodicarbonamide in rats. Fundam Appl Toxicol; 8 (3). 372-381.

International research and Development Corporation (IRDC), biological disposition of orally administered azodicarbonamide in male rats, unpublished report to the National Toxicology Program, Report No. 5702-125, 1982.

Medinsky et al., (1990) Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures Fundamental and Applied Toxicology 15, pages 308-319.

OECD SIDS Initial assessment report for SIAM 12, 2001. Azodicarbonamide.WHO IPCS,

Concise International Chemical Assessment Document (CICAD) 16. 1999. Azodicarbonamide.