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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The analogue CAS nº 36549-48-1 monosodium salt of cyanuric acid, monohydrate, shares the same functional group with the substance CAS nº 3047-33-4 trisodium cyanurate and the results can be extrapolated to trisodium cyanurate.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
other: read-across
Title:
Unnamed
Year:
2010

Materials and methods

Principles of method if other than guideline:
Read-across approach from a study report (using the methods outlined by EU Method B.36) on the analogue CAS nº 36549-48-1 monosodium salt of cyanuric acid, monohydrate.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): monosodium salt of cyanuric acid, monohydrate
- Molecular formula (if other than submission substance): C3H3N3O3.H2O.Na
- Molecular weight (if other than submission substance): 170.08
- Smiles notation (if other than submission substance): Na].O.O=C1NC(=O)NC(=O)N1
- InChl (if other than submission substance):
InChI=1/C3H3N3O3.Na.H2O/c7-1-4-2(8)6-3(9)5-1;;/h(H3,4,5,6,7,8,9);;1H2
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Sodium cyanurate was totally absorbed after administration at 5 mg/kg p.o but absorption after administration at 500 mg/kg p.o was highly variable ranging from less than 10% of the dose to total absorption with an average of around 50% of the dose absorbed. After repeated administration of the compound at 5 mg/kg p.o absorption of the final 14C-labeled dose was marginally reduced. Absorption was determined by comparison of the urinary recovery of the compound after i.v and p.o administration, and by comparison of the areas under the 0-8 hr blood concentration-time curves after i.v and p.o administration.
Details on distribution in tissues:
The concentrations of sodium cyanurate equivalents in tissues at the time of animal sacrifice were less than the limits of sensitivity for the assay for all treatment regimens.
Details on excretion:
After iv or oral administration at 5 mg/kg sodium cyanurate compound equivalents were primarily excreted via the urinary route during the first 12 h with only marginal excretion occurring after 24 h. The percentage of dose excreted in the urine was similar after either route of administration. Recovery of sodium cyanurate equivalents in the feces was negligible ie 2% of the dose or less except for three of the multiple dose animals in which 6-13% was recovered via the fecal route. The total percentage of the 5 mg/kg dose recovered in the urine and feces of both sexes varied from 80 to 100%. Similar total recoveries were observed after oral adminitsration of the compound at 500 mg/kg. However, the percentage excreted in the urine after the higher dose varied from as low as 14% to a maximum of 73%. Urinary excretion of compound equivalents occurred primarily during the first 24 h after dosing, with only marginal excretion occurring after 48 h. There were no differences between the urinary excretion patterns of males and females.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Only parent compound was found in urine indicating that metabloism of sodium cyanurate did not occur or was minimal.

Any other information on results incl. tables

Sodium cyanurate was rapidly absorbed, with peak blood levels 1-3 hours post dose and a single elimination half life of 1.5-2 h.  Absorption was probably rate limiting, thus tmax was later and the terminal half-life was longer in high dose animals.

Sodium cyanurate was completely absorbed following administration at 5mg/kg to dogs, but absorption was highly variable at the 500 mg/kg dose level, averaging ~ 50%.  The absorbed compound was rapidly and almost quantitatively eliminated in the urine.

Metabolism, if it occurred at all, is negligible.

There is no evidence for bioaccumulation of the compound and there are no major changes in the disposition or metabolism of sodium cyanurate following repeated administration.

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid, monohydrate (there is no evidence for bioaccumulation of the compound and there are no major changes in the disposition or metabolism of sodium cyanurate following repeated administration) the read-across approach is applied and the same results can be extrapolated for trisodium cyanurate, under test conditions.

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0.(see attachment).

 

Table 1: Data Matrix, Analogue Approach.

CAS Number

 

36549-48-1

3047-33-4

CHEMICAL NAME

 

Analogue 3

Sodium cyanurate monohydrate

 

Trisodium cyanurate

PHYSICO-CHEMICAL DATA

Melting Point

No data

Estimated data:

260.74ºC

Boiling Point

No data

Estimated data:

603.07ºC

Density

No data

  Experimental results:

2.09g/mL

 

Vapour Pressure

No data

Estimated data:

1.62E-013 mm Hg at 25ºC

Partition Coefficient (log Kow)

No data

Estimated data:

-2.06

Water solubility

 

No data

Estimated data:

1E+006 mg/L at 25 ºC

ENVIRONMENTAL FATE and PATHWAY

Aerobic Biodegradation

 

No data

 

Read-across from Cyanuric acid:

Normally it degrades very slowly under aerobic conditions. 

Nevertheless, it can be readily degraded aerobically under nitrogen-limited conditions, but only by a number of microorganisms in certain conditions.

 

Anaerobic Biodegradation

No data

 

Read-across from Cyanuric acid:

Ready biodegradability

ENVIRONMENTAL TOXICITY

Acute Toxicity to Fish

No data

 

Read-across from Cyanuric acid:

96 h-LC50 > 1510 mg/L

 

Acute Toxicity to Aquatic Invertebrates

No data

Read-across from Cyanuric acid:

48 h-LC50 > 1510 mg/L

 

Toxicity to Aquatic Plants

 

Experimental data:

 

72h-EbC50= 2700 mg/L, basis for effect: biomass

96h-EbC50 > 5000 mg/L, basis for effect: biomass

72h- ErC50 > 5000 mg/L, basis for effect: growth rate

96h- ErC50 > 5000 mg/L, basis for effect: growth rate

72h- NOEC = 1250 mg/L, basis for effect: growth rate

96h- NOEC = 5000 mg/L, basis for effect: growth rate

 

Read-across from Cyanuric acid:

96 h-EC50=1075 mg/L (basis for effect: in vivo chlorophyll)

96 h-EC50=989.6 mg/L (basis for effect: cell number)

 

Read-across from Sodium cyanurate:

72h-EC50 > 128.2 mg/L

Read-across from Sodium cyanurate monohydrate:

 

72h-EbC50= 3095.7 mg/L, basis for effect: biomass

96h-EbC50 > 5708.4 mg/L, basis for effect: biomass

72h- ErC50 > 5708.4 mg/L, basis for effect: growth rate

96h- ErC50 > 5708.4 mg/L, basis for effect: growth rate

72h- NOEC = 1433.1 mg/L, basis for effect: growth rate

96h- NOEC = 5708.4 mg/L, basis for effect: growth rate

MAMMALIAN TOXICITY

Acute Oral

No data

Read-across from Cyanuric acid:

LD50 > 7554.42 mg/kg bw

 

Acute Inhalation

No data

Read-across from Cyanuric acid:

LC50 > 7.93 mg/L

 

Acute Dermal

No data

Read-across from Cyanuric acid:

LD50 > 7554.42 mg/kg bw

Repeated Dose

Repeated dose toxicity: oral:

Key study: mouse, 13 weeks:

NOAEL = 5375 ppm

 LOAEL < 5375 ppm

Key study: rat, 104 weeks:

NOAELca. 154 mg/kg bw/day, male

NOAEL ca. 266 mg/kg bw/day, female

LOAEL ca. 371 mg/kg bw/day, male

LOAEL ca. 634 mg/kg bw/day, female

 

 

 

 

Read-across from Cyanuric acid:

 

NOAEL ca 349 mg/kg bw/day male

NOAEL ca. 1380.9 mg/kg bw/day female

Read-across from Sodium cyanurate:

 

LOAEL > 5128.8 ppm

NOAEL = 5128.8 ppm

Read-across from Sodium cyanurate:

 

NOAELca. 1952.8 mg/kg bw/day,male

NOAELca. 2028.4 mg/kg bw/day, female

Read-across from Sodium cyanurate monohydrate:

 

NOAEL = 6162.5 ppm

 LOAEL < 6162.5 ppm

Read-across from Sodium cyanurate monohydrate:

 

NOAELca. 176.5 mg/kg bw/day, male

NOAEL ca. 304.9 mg/kg bw/day, female

LOAEL ca. 425.3 mg/kg bw/day, male

LOAEL ca. 726.8 mg/kg bw/day, female

Genetic Toxicity in vitro

 

-         Gene mutation in bacteria

 

Key study: 

Salmonella, with and without metabolic activation, genotoxicity negative, no citotoxicity

 

Read-across from Sodium cyanurate:

Negative

 

Read-across from Sodium cyanurate monohydrate:

Negative

-         Mammalian gene mutation

 

No data

 

Read-across from Sodium cyanurate:

Negative

Chromosomal aberration

No data

Read-across from Sodium cyanurate:

Negative

Genetic Toxicity in vivo

 

No data

 

Read-across from Sodium cyanurate:

Negative

 

Carcinogenicity

 

Key study:

Rat, 104 weeks

NOAEL ca. 154 mg/kg bw/day, male

NOAEL ca. 266 mg/kg bw/day, female

 

Read-across from Sodium cyanurate:

NOAEL ca. 1520  mg/kg bw/day, male

NOAEL ca. 1580 mg/kg bw/day, female

Read-across from Sodium cyanurate monohydrate:

NOAEL ca. 176.5 mg/kg bw/day, male

NOAEL ca. 304.9 mg/kg bw/day, female

Reproductive Toxicity

No data

 

Read-across from Sodium cyanurate:

 

NOAEL:

 

P male ca.  602.6 mg/kg bw/day

P female  ca. 1218 mg/kg bw/day

F1 male  ca. 641.1 mg/kg bw/day

F1 female  ca. 1166.8 mg/kg bw/day

F2 male  ca. 243.6 mg/kg bw/day

F2 female  ca. 1243.7 mg/kg bw/day

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
There is no evidence for bioaccumulation of the compound and there are no major changes in the disposition or metabolism of sodium cyanurate following repeated administration.
The same result can be extrapolated for trisodium cyanurate.
Executive summary:

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid, monohydrate (there is no evidence for bioaccumulation of the compound and there are no major changes in the disposition or metabolism of sodium cyanurate following repeated administration) the read-across approach is applied and the same results can be extrapolated for trisodium cyanurate, under test conditions.