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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
other: read-across from an in vivo 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 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 OECD Guideline 429) on the analogue CAS nº 108-80-5 cyanuric acid.
GLP compliance:
yes
Type of study:
other: read-across from an in vivo study with an analogue

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Any other information on results incl. tables

Based on the experimental results obtained with the analogue cyanuric acid (stimulation index of ≤ 3) (based on the severity of the response the positive results were considered indicators of borderline or mild skin sensitization potential), the read-across approach is applied and the same results can be extrapolated to substance trisodium cyanurate under test conditions.

The analogue cyanuric acid shares the same functional group with the substance CAS nº 3047-33-4 trisodium cyanurate, which 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-2.06for trisodium cyanurate, 

- a high water solubility which is 2000 mg/L at 25 ºC for cyanuric acid and1E+006 mg/L at 25 ºCfor trisodium cyanurate

- similar molecular weights which are 129.07 for cyanuric acid 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

 

108-80-5

3047-33-4

CHEMICAL NAME

 

Analogue 1

Cyanuric acid

 

Trisodium cyanurate

PHYSICO-CHEMICAL DATA

Melting Point

Experimental results:

320 - 440°C

Estimated data:

260.74ºC

Boiling Point

No data

Estimated data:

603.07ºC

Density

Experimental results:

1.75g/ml

  Experimental results:

2.09g/mL

Vapour Pressure

No data

 

Estimated data:

1.62E-013 mm Hg at 25ºC

Partition Coefficient (log Kow)

Experimental results:

-1.31 at 25°C

Estimated data:

-2.06

Water solubility

 

Experimental results:

2000 mg/L at

 

Estimated data:

1E+006 mg/L at 25 ºC

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 biodegreadability

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 > 1510 mg/L

 

Acute Toxicity to Aquatic Invertebrates

Experimental data:

48 h-LC50 > 1000 mg/L

Read-across from Cyanuric acid:

48 h-LC50 > 1510 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)

 

 

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

Key study:

LD50 > 5000 mg/kg bw

Read-across from Cyanuric acid:

LD50 > 7554.42 mg/kg bw

 

Acute Inhalation

Key study:

LC50 > 5.25 mg/L

 

Read-across from Cyanuric acid:

LC50 > 7.93 mg/L

 

Acute Dermal

Key study:

LD50 > 5000 mg/kg bw

Read-across from Cyanuric acid:

LD50 > 7554.42 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

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

 

No data

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

 

No data

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

Interpretation of results:
other: mild sensitiser
Conclusions:
The stimulation index for substance trisodium cyanurate is considered to be ≥ 3. Based on the severity of the response the positive results were considered indicators of borderline or mild skin sensitisation.
Executive summary:
Based on the experimental results obtained with the analogue cyanuric acid (stimulation index of ≤ 3) (based on the severity of the response the positive results were considered indicators of borderline or mild skin sensitization potential), the read-across approach is applied and the same results can be extrapolated to substance trisodium cyanurate under test conditions.