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Diss Factsheets
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EC number: 204-650-8 | CAS number: 123-77-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Specific investigations: other studies
Administrative data
- Endpoint:
- endocrine system modulation
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Documentation insufficient for assessment (no data on purity, no data on food consumption, i.e. on ADCA exposure, lack of data on animals and methods)
Data source
Reference
- Reference Type:
- publication
- Title:
- Effect of Azodicarbonamide (1,1'-Azobisformamide) on Thyroid Function
- Author:
- Gafford FH, Sharry PM, Pittman JA
- Year:
- 1 971
- Bibliographic source:
- Clin Endocrinol Metab. 1971, May; 32(5):659-62
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- GLP compliance:
- no
- Type of method:
- in vivo
- Endpoint addressed:
- repeated dose toxicity: oral
Test material
- Reference substance name:
- C,C'-azodi(formamide)
- EC Number:
- 204-650-8
- EC Name:
- C,C'-azodi(formamide)
- Cas Number:
- 123-77-3
- Molecular formula:
- C2H4N4O2
- IUPAC Name:
- diazene-1,2-dicarboxamide
- Details on test material:
- ADA (Azodicarbonamide) and BiU (Biurea)
Supplied by Aldrich Chemical-Company, Inc., Cedar Knolls, N. J.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Weight at study initiation: 160-180 g
Administration / exposure
- Route of administration:
- other: in diet and IP
- Vehicle:
- other: in diet of propylene glycol (IP)
- Details on exposure:
- In diet: Rats were maintained on a low iodine diet (Remington, General Blochemicals Incorporated, Chagrin Falls. Ohio).
IP: The volume of propylene glycol injected was 0.1 ml/100 g body wt/day for both control and experimental groups. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10 days or 4weeks
- Frequency of treatment:
- ad lib or daily
- Post exposure period:
- none
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
1, 5 and 10% ADA
Basis:
nominal in diet
in diet
- Remarks:
- Doses / Concentrations:
5 and 10% BiU
Basis:
nominal in diet
in diet
- Remarks:
- Doses / Concentrations:
20. 2 and 0.2mg ADA/100 g body wy
Basis:
nominal conc.
IP
- Remarks:
- Doses / Concentrations:
20 and 2 mg BiU/100g body wt
Basis:
nominal conc.
IP
- Control animals:
- yes, concurrent vehicle
- yes, plain diet
- Details on study design:
- One day prior to the end of each experiment 0.1 pCi of 125I in isotonic saline was given ip to each rat.
The following day all rats were sacrificed with ether anesthesia and their thyroids removed and weighed.
Examinations
- Examinations:
- Twenty-four hr thyroidal radioiodine uptakes were determined by counting thyroids and standards in an automatic well counter (NuclearChicago).
PBIs on pooled group plasma samples were determined for some of the experiments (Techniccn AutoAnalyaer), Plasma TSH levels were also determined from these pooled group plasma samples by radioimmunoassay. - Positive control:
- In one experiment, a positive control group received a low iodine diet containing 0.1 %methimazole (MMI).
Results and discussion
Any other information on results incl. tables
The ADA-treated-groups had thyroidal radioiodine uptakes which tended in all cases to be lower than the controls at dietary levels of 1, 5 and 10% ADA. The decrease was statistically significant in those groups which received 5 or 10% ADA in experiments lasting 10 days or 4 weeks. However, there was no concomitant thyroid enlargement, except in one experiment of one week's duration in which the total body weight of the test animals was significantly reduced by about 10%.
The latter effect contributed to the relative thyromegaly in the one treated group which showed goiter (the group receiving 10% ADA).
Thyroid weights per rat in this experiment (means ±SD) for the controls, 1% ADA and 10% ADA were 22.6 ±5.7, 26.0 ±3.2 and 28.0±7.6 mg, respectively. The possible goitrogenesis in the 10% ADA group in this experiment was not nearly so striking as that seen with methimazole administration, and in a 10-day 5% ADA group there was a slight but statistically significant reduction in thyroid weight.
In the 4-week, 10% ADA experiment there was no significant change in thyroid weight from control values. The serum protein bound iodine concentrations (PBI) on pooled samples tended to be lower in the test animals.
Oral administration of BiU at levels of 5 and 10% of the diet did not significantly alter thyroidal radioiodine uptakes after 1 week or 10 days, nor did goiter develop or PBI fall.
No significant alterations of thyroid uptake, thyroid weight, or plasma PBI were seen. A dose of 20 mgADA/100 g body wb/day killed 5 of 6 rats during the course of 1 week. No deaths occurred until day 3 of the experiment, and each was preceded by 24-48 hr of macroscopic hematuria. The mode of onset of these deaths indicated a possible cumulative toxicity of ADA when administered parenterally at high dose levels. Thyroid function data on the 3 surviving rats appeared similar to control values. However, reduction of the dose of ADA by factors of 10 and 100 eliminated all systemic signs of toxicity (anorexia, weight loss and gross hematuria) and gave clear evidence of thyroid function similar to controls, as did BiU in doses of 2 and 20 mg/100 g body wt/day. Plasma TSH levels were determined on pooled samples for which PBI data are also shown, and the plasma TSH did not rise significantly (remained below the limit of detectability, 80 µU/ml).
Thus, ADA, given as 5 or 10% of the diet for 10 or 28 days, was found to weakly inhibit thyroidal radioiodine uptake. The magnitude of this effect was much smaller and less consistent than the depression of uptakes seen with administration of potent antithyroid agents such as methimazole (MMI), propylthiouracil (P'TIJ), or aminotriazole (ATZ).
Inhibition of uptake by ADA occurred only at dose levels much higher than the minimal effective doses of MMI, PTU, or ATZ. Although there was a tendency to reduced serum PBIs in the ADA groups, this was not marked, and direct estimates of serum TSH showed no increase. There was no consistent goitrogenesis, and the mechanism for the reduction in thyroidal radioiodine uptake by ADA is not established. Depression of the 24-hr uptake is an earlier and more sensitive measure of antithyroid activity than increased serum TSH, goiter formation, or decreased PBI, and the most likely explanation for the reduced uptakes seen in these studies is that ADA does in fact have a weak antithyroid action.
Although many extrathyroid factors can affect the uptake (stress, renal insufficiency, cardiac decompensation, changes in fecal bulk, altered stable iodine intake, etc.), no evidence of any of these was observed in the present experiments, and the rats appeared clinically healthy while receiving the diet containing 10% ADA.
There was no evidence that BiU altered thyroid function in any way.
The apparent antithyroid effect of ADA in these experiments is of no significance in relation to its use in the baked goods industry. For example, at the highest permissible level of use (45 ppm), bread containing 75% flour would have only 33.75 mg ADA/kg of bread; and the minimal effective dose of ADA needed to depress thyroid uptake in the rat was 50 g/kg of rat chow. In addition, ADA is converted to BiU when water is added to the flour, and further conversion occurs when the temperature in the baking oven exceeds 180 C. Thus, the question of antithyroid activity of ADA is now of interest only in connection with a possible structure-activity relation to known antithyroid agents. These' experiments show that there would be no ill effects from any such antithyroid activity of ADA in the quantities in which it is used commercially.
Applicant's summary and conclusion
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