1,3,5-triazine-2,4,6(1H,3H,5H)-trione, trisodium salt

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The analogue CAS nº 2624-17-1 monosodium salt of cyanuric acid 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 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 on the analogue CAS nº 2624-17-1 monosodium salt of cyanuric acid.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

s-triazinetriol monosodium salt (cyanuric acid, monosodium salt)

IUPAC Name:

s-triazinetriol monosodium salt (cyanuric acid, monosodium salt)

Constituent 2

Reference substance name:

2624-17-1

Cas Number:

2624-17-1

IUPAC Name:

2624-17-1

Details on test material:

- Name of test material (as cited in study report): monosodium salt of cyanuric acid
- Molecular formula (if other than submission substance): C3H3N3O3 Na
- Molecular weight (if other than submission substance): 152.08
- Smiles notation (if other than submission substance): [nH-]1c([nH]c(=O)[nH]c1=O)=O.[Na+]
- InChl (if other than submission substance): 1/C3H3N3O3.Na/c7-1-4-2(8)6-3(9)5-1;/h(H3,4,5,6,7,8,9);/q;+1/p-1
- Structural formula attached as image file (if other than submission substance): see Fig

Administration / exposure

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:

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):

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:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

> 5 128.8 ppm

Sex:

male/female

Basis for effect level:

other: LOAEL >797 mg/kg bw/d (males); >1097mg/kg bw/d (females)

2

Dose descriptor:

NOAEL

Effect level:

5 128.8 ppm

Sex:

male/female

Basis for effect level:

other: NOAEL 797 mg/kg bw/d (males); 1097 mg/kg bw/d (females)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid (LOAEL > 4000 ppm and NOAEL = 4000 ppm) , the read-across approach is applied and the LOAEL and NOAEL for substance trisodium cyanurate are calculated to be higher than 5128.8 ppm and 5128.8 ppm, respectively, under test conditions.

.

The analogue sodium cyanurate shares the same functional group with trisodium cyanurate, that also has comparable values for the relevant molecular properties. These properties are: 

- a low log Pow value which is 0.62for sodium cyanurate and -2.06 for trisodium cyanurate,

- a high water solubility which is 2.234E+004 mg/Lfor sodium cyanurate and 1E+006 mg/L for trisodium cyanurate at 25ºC,

- similar molecular weights which are152.08 for sodium cyanurate and 195.01 for trisodium 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” version 1.1.0. (see attachment).

 

Table 1: Data Matrix, Analogue Approach.

CAS Number		2624-17-1	3047-33-4
CHEMICAL NAME		Analogue 2 Sodium cyanurate	Trisodium cyanurate
PHYSICO-CHEMICAL DATA
Melting Point		Estimated data: 305ºC	Estimated data: 260.74ºC
Boiling Point		Estimated data: 697.8ºC	Estimated data: 603.07ºC
Density		No data	Experimental results: 2.09g/mL
Vapour Pressure		Estimated data: 1.41E-016 mm Hg at 25ºC	Estimated data: 1.62E-013 mm Hg at 25ºC
Partition Coefficient (log Kow)		Estimated data: 0.62	Estimated data: -2.06
Water solubility		Estimated data: 2.234E+004 mg/L at 25ºC	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 limited 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-EC50 > 100 mg/L  72h-NOEC = 100 mg/L	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  72h-NOEC = 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: 28 days extended to 59 days in rats: LOAEL > 4000 ppm NOAEL = 4000 ppm Repeated dose toxicity oral: Key study: 104 weeks in mouse: NOAELca. 1523 mg/kg bw/day,male NOAELca. 1582 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	Supporting study:  Salmonella, with and without metabolic activation, genotoxicity negative	Read-across from Sodium cyanurate: Negative   Read-across from Sodium cyanurate monohydrate: Negative
	-         Mammalian gene mutation	Key study: CHO, with and without metabolic activation, genotoxicity negative	Read-across from Sodium cyanurate: Negative
	Chromosomal aberration	Key study: Mouse lymphoma L5178Y cells, with and without metabolic activation, genotoxicity negative	Read-across from Sodium cyanurate: Negative
Genetic Toxicity in vivo		Key study: Rat bone marrow cytogenetics assay, genotoxicity negative	Read-across from Sodium cyanurate: Negative
Carcinogenicity		Key study: Mouse, 104 weeks NOAEL ca. 1520  mg/kg bw/day, male NOAEL ca. 1580 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		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	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:

The LOAEL and NOAEL for substance trisodium cyanurate are calculated to be higher than 5128.8 ppm and 5128.8 ppm, respectively ( LOAEL >797 mg/kg bw/d (males); >1097mg/kg bw/d (females) NOAEL 797 mg/kg bw/d (males); 1097 mg/kg bw/d (females)).

Executive summary:

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid (LOAEL > 4000 ppm and NOAEL = 4000 ppm), the read-across approach is applied and the LOAEL and NOAEL for substance trisodium cyanurate are calculated to be higher than 5128.8 ppm and 5128.8 ppm. respectively, under test conditions ( LOAEL >797 mg/kg bw/d (males); >1097mg/kg bw/d (females) NOAEL 797 mg/kg bw/d (males); 1097 mg/kg bw/d (females)).