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Repeated dose toxicity: oral

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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:
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

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
- 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

open allclose all
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)
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)).