Cary, R; Dobson, S; Ball, M
This CICAD on azodicarbonamide was based on a review of human health (primarily occupational) concerns prepared by the United Kingdom's Health and Safety Executive (Ball et al., 1996). Hence, although this CICAD includes an assessment of the available environmental data, the main focus is on risks to human health in the working environment, including an emphasis on information from routes that are relevant to occupational settings. Data identified up to June 1994 were covered in the review. A further literature search was performed, up to July 1997, to identify any new information published since this review was completed. The original source document did not address environmental concerns; as literature searches have failed to identify relevant studies in this area, an environmental risk assessment has not been attempted. Information on the nature of the peer review and availability of the source document is presented in Appendix 1. Information on the peer review of this CICAD is presented in Appendix 2. This CICAD was approved as an international assessment at a meeting of the Final Review Board, held in Tokyo, Japan, on 30 June - 2 July 1998. Participants at the Final Review Board meeting are listed in Appendix 3. The International Chemical Safety Card (ICSC 0380) for azodicarbonamide, produced by the International Programme on Chemical Safety (IPCS, 1993), has also been reproduced in this document. Toxicokinetic data on azodicarbonamide (CAS No. 123-77- 3) are limited, but the chemical appears to be well absorbed by the inhalation and oral routes in rodents. Substantial quantities of the substance remain unabsorbed from the gastrointestinal tract and are passed out in the faeces. Azodicarbonamide is readily converted to biurea, the only breakdown product identified, and it is likely that systemic exposure is principally to this derivative rather than to the parent compound. Elimination of absorbed azodicarbonamide/biurea is rapid, occurring predominantly via the urine, and there is very little systemic retention of biurea. Azodicarbonamide is of low acute toxicity and does not cause skin, eye, or respiratory tract irritation in experimental animals. Results from a poorly conducted skin sensitization study were negative, and there was no evidence of an asthmatic-type response in guinea-pigs in one study. No adverse effects were observed in experimental animals inhaling up to 200 mg/m3 for up to 13 weeks. Repeated oral exposures resulted in the appearance of pyelonephritis with casts and crystalline deposits in renal tubuli in several species. However, the dose levels required to induce these effects were high (>200 mg/kg body weight per day in studies of up to 1 year's duration). Although azodicarbonamide was found to be a mutagen n bacterial systems, there is no evidence that this effect would be expressed in vivo. The carcinogenicity and reproductive toxicity of azodicarbonamide have not been examined in detail, but no tumorigenic or antifertility effects were observed in early studies in which animals were treated with the breakdown product biurea. Developmental toxicity has not been studied. Studies in humans have concentrated solely on the ability of azodicarbonamide to induce asthma and skin sensitization. Evidence that azodicarbonamide can induce asthma in humans has been found from bronchial challenge studies with symptomatic individuals and from health evaluations of employees at workplaces where azodicarbonamide is manufactured or used. There are also indications that azodicarbonamide may induce skin sensitization. On the basis that azodicarbonamide is a human asthmagen and that the concentrations required to induce asthma in a non-sensitive individual or to provoke a response in a sensitive individual are unknown, it is concluded that there is a risk to human health under present occupational exposure conditions. The level of risk is uncertain; hence, exposure levels should be reduced as much as possible. Data have been identified that indicate ethyl carbamate formation in consumer products such as bread and beer following the addition of azodicarbonamide. Exposure of the general public to azodicarbonamide could not be evaluated because of the lack of available data. Azodicarbonamide released to surface waters would partition to the hydrosphere with no significant sorption to particulates. The half-life for reaction with hydroxyl radicals in the atmosphere is calculated to be 0.4 days. Azodicarbonamide was readily biodegradable in two out of three tests with sewage sludge and was degraded in soil by 20-70% over 14 days. No- observed-effect concentrations (NOECs) for fish and the water flea have been reported at >50 and 5 mg/litre, respectively. Lack of information on release to the environment precludes a quantitative risk assessment.
surface water; urea derivative; asthma; atmosphere; chemical analysis; conference paper; environmental exposure; health hazard; human; nonhuman; pathogenesis; risk assessment; safety; skin sensitization; work environment; world health organization; Animalia; Bacteria (microorganisms); Cavia; Cladocera; Rodentia; Siphonaptera (fleas)