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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
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.

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 OECD Guideline 475) on the analogue CAS nº 2624-17-1 monosodium
salt of cyanuric acid.
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
- 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

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative

Any other information on results incl. tables

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid (male, genotoxicity negative) and the molecular weights, the read-across approach is applied and the same results can be extrapolated to substance trisodium cyanurate, 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:
Interpretation of results (migrated information): negative
Trisodium cyanurate was negative.
Executive summary:

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid (male, genotoxicity negative) and the molecular weights, the read-across approach is applied and the same results can be extrapolated to substance trisodium cyanurate, under test conditions.