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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
genetic toxicity in vitro
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 the proposed guidelines for registering pèsticides in the U.S.) on the analogue CAS nº 36549-48-1 monosodium salt of cyanuric acid, monohydrate.
GLP compliance:
no
Type of assay:
other: read –across form a bacterial reverse mutation assay on analogue

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.

Method

Details on test system and conditions:
METHOD OF APPLICATION: In agar (plate incorporation)







Results and discussion

Test results
Species / strain:
other: TA100 Spot test: S. typhimurium: TA1535, TA1537, TA97, TA98 and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no

Any other information on results incl. tables

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid, monohydrate (S. typhimurium: TA100 Spot test: S. typhimurium: TA1535, TA1537, TA97, TA98 and TA100, with and without metabolic activation, genotoxicity negative, no citotoxicity) , the read-across approach is applied and the same results can be extrapolated for substance 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):
negative

Trisodium cyanurate was negative.
Executive summary:

Based on the experimental results obtained with the analogue monosodium salt of cyanuric acid, monohydrate (S. typhimurium: TA100 Spot test: S. typhimurium: TA1535, TA1537, TA97, TA98 and TA100, with and without metabolic activation, genotoxicity negative, no citotoxicity) the read-across approach is applied and the same results can be extrapolated for substance trisodium cyanurate, under test conditions.