sodium 1,3,5-triazinane-2,4,6-trione

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: read-across from a subchronic study with an analogue

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The analogue CAS nº 108-80-5 cyanuric acid shares the same functional group with the substance CAS nº 2624-17-1 sodium cyanurate and the results can be extrapolated to sodium cyanurate.

Cross-reference

Reason / purpose for cross-reference:

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 the OECD Guideline 408) on the analogue CAS nº 108-80-5 cyanuric acid

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyanuric acid

EC Number:

203-618-0

EC Name:

Cyanuric acid

Cas Number:

108-80-5

Molecular formula:

C3H3N3O3

IUPAC Name:

1,3,5-triazinane-2,4,6-trione

Details on test material:

- Name of test material (as cited in study report): Cyanuric acid
- Molecular formula (if other than submission substance): C3H3N3O3
- Molecular weight (if other than submission substance): 129.07
- Smiles notation (if other than submission substance): O=C1NC(=O)NC(=O)N1
- InChl (if other than submission substance): 1/C3H3N3O3/c7-1-4-2(8)6-3(9)5-1/h(H3,4,5,6,7,8,9)
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

Based on the experimental results obtained with the analogue cyanuric acid (NOAEL ca.231 mg/kg bw/day male; NOAEL ca. 914 mg/kg bw/day female; LOAEL ca. 109 mg/kg bw/day male; LOAEL ca. 915 mg/kg bw/day female), the read-across approach is applied and the NOAEL and LOAEL for substance sodium cyanurate are calculated to be NOAEL ca 272 mg/kg bw/day male; NOAEL ca. 1076 mg/kg bw/day female; LOAEL ca. 128 mg/kg bw/day male; LOAEL ca. 1078 mg/kg bw/day female under test conditions.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

ca. 272 mg/kg bw/day (nominal)

Sex:

male

2

Dose descriptor:

NOAEL

Effect level:

ca. 1 076 mg/kg bw/day (nominal)

Sex:

female

3

Dose descriptor:

LOAEL

Effect level:

ca. 128 mg/kg bw/day (nominal)

Sex:

male

4

Dose descriptor:

LOAEL

Effect level:

ca. 1 078 mg/kg bw/day (nominal)

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The analogue cyanuric acid shares the same functional group with the substance CAS nº 2624-17-1 sodium cyanurate and also has comparable values for the relevant molecular properties. These properties are:

 

- a low log Pow value which is -1.31 for cyanuric acid and 0.62 for sodium cyanurate,

 

- a high water solubility which is 2000 mg/L at 25 ºC for cyanuric acid and 22300 mg/L at 25 ºC for sodium cyanurate and

 

- similar molecular weights which are129.07 for cyanuric acid and 152.08 for sodium cyanurate.

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” (see attachment).

 

Table 1: Data Matrix, Analogue Approach

 

CAS Number		108-80-5	2624-17-1
CHEMICAL NAME		Analogue 1 Cyanuric acid	Sodium cyanurate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 320 - 440°C	Estimated data: 305ºC
Boiling Point		No data	Estimated data: 697.8ºC
Density		Experimental results: 1.75 g/ml	Experimental results: 1.9 g/ml
Vapour Pressure		No data	Estimated data: 1.41E-016 mm Hg at 25ºC
Partition Coefficient (log Kow)		Experimental results: -1.31 at 25°C	Estimated data: 0.62
Water solubility		Experimental results: 2000 mg/L at 25 ºC	Estimated data: 2.234E+004 mg/L at 25ºC
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Experimental results: Normally it degrades very slowly under aerobic conditions.  Nevertheless, it can be readily degraded aerobically under nitrogen-limited conditions, but only by a limited number of microorganisms in certain conditions.	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 limited number of microorganisms in certain conditions.
Anaerobic Biodegradation		Experimental results: Ready biodegradability	Read-across from Cyanuric acid: Ready biodegradability
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Experimental data: 96 h-LC50 > 1000 mg/L	Read-across from Cyanuric acid: 96 h-LC50 > 1178 mg/L
Acute Toxicity to Aquatic Invertebrates		Experimental data: 48 h-LC50 > 1000 mg/L	Read-across from Cyanuric acid: 48 h-LC50 > 1178 mg/L
Toxicity to Aquatic Plants		Experimental data: 96 h-EC50=712 mg/L (basis for effect: in vivo chlorophyll) 96 h-EC50=655 mg/L (basis for effect: cell number)	Experimental data: 72h-EC50 > 100 mg/L 72h-NOEC = 100 mg/L Experimental data: Sodium cyanurate monohydrate   72h-EbC50= 2700 mg/L (biomass) 72h- ErC50 > 5000 mg/L (growth rate) 72h- NOEC = 1250 mg/L (growth rate)
MAMMALIAN TOXICITY
Acute Oral		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 mg/kg bw
Acute Inhalation		Key study: LC50 >5.25mg/L	Read-across from Cyanuric acid: LC50 >6.19mg/L
Acute Dermal		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 mg/kg bw
Repeated Dose		Repeated dose toxicity: oral: Key study: 13 weeks in rats: NOAEL ca.231 mg/kg bw/day male NOAEL ca. 914 mg/kg bw/day female	Repeated dose toxicity: oral: Key study: 28 days extended to 59 days in rats: LOAEL > 4000 ppm NOAEL = 4000 ppm Repeated dose toxicity oral: Key study: 104 weeks in mouse: NOAEL ca. 1520 mg/kg bw/day,male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks   NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Genetic Toxicity in vitro	Gene mutation in bacteria	No data	Key study: Sodium cyanurate monohydrate: Negative
	Mammalian gene mutation	No data	Key study: CHO, with and without metabolic activation, genotoxicity negative
	Chromosomal aberration	No data	Key study: Mouse lymphoma L5178Y cells, with and without metabolic activation, genotoxicity negative
Genetic Toxicity in vivo		No data	Key study: Rat bone marrow cytogenetics assay, genotoxicity negative
Carcinogenicity		No data	Key study: Mouse, 104 weeks NOAEL ca. 1520  mg/kg bw/day, male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Reproductive Toxicity		No data	Key study: Rats, 100 and 120 days exposure- period of F0, F1 and F2 generations, both sexes.  NOAEL: P male ca.  470 mg/kg bw/day P female  ca. 950 mg/kg bw/day F1 male  ca. 500 mg/kg bw/day F1 female  ca. 910 mg/kg bw/day F2 male  ca. 190 mg/kg bw/day F2 female  ca. 970 mg/kg bw/day   Key study: Rabbit, developmental toxicity. NOAEL maternal = 50 mg/kg bw/day NOAEL teratogenicity = 500 mg/kg bw/day Key study: Sodium cyanurate monohydrate: Rat, developmental toxicity: NOAEL maternal = 5000 mg/kg bw/day NOAEL teratogenicity = 5000 mg/kg bw/day

 

 

Applicant's summary and conclusion

Conclusions:

The NOAEL and LOAEL for substance sodium cyanurate are calculated to be: NOAEL ca 272 mg/kg bw/day male; NOAEL ca. 1076 mg/kg bw/day female; LOAEL ca. 128 mg/kg bw/day male; LOAEL ca. 1078 mg/kg bw/day female.

Executive summary:

Based on the experimental results obtained with the analogue cyanuric acid (NOAEL ca.231 mg/kg bw/day male; NOAEL ca. 914 mg/kg bw/day female; LOAEL ca. 109 mg/kg bw/day male; LOAEL ca. 915 mg/kg bw/day female) the read-across approach is applied and the NOAEL and LOAEL for substance sodium cyanurate are calculated to be NOAEL ca 272 mg/kg bw/day male; NOAEL ca. 1076 mg/kg bw/day female; LOAEL ca. 128 mg/kg bw/day male; LOAEL ca. 1078 mg/kg bw/day female under test conditions.