sodium 1,3,5-triazinane-2,4,6-trione

Endpoint summary

Description of key information

Read-across from in vivo studies of skin and eye irritation (where cyanuric acid was non-irritating). The same results can be extrapolated to sodium cyanurate.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

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:

2 (reliable with restrictions)

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 2624-17-1 sodium cyanurate and the results can be extrapolated to sodium cyanurate

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from a study report (using the methods outlined by the OECD Guideline 404) on the analogue CAS nº 108-80-5 cyanuric acid

GLP compliance:

no

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 72 h

Score:

0

Based on the experimental results obtained with the analogue cyanuric acid (72h-primary dermal irritation index (PDII)= 0), the read-across approach is applied and the 72h-primary dermal irritation index (PDII) for substance sodium cyanurate is considered to be 0 under test conditions.

  The analogue cyanuric acid shares the same functional group with the substance CAS nº 2624-17-1 sodium cyanurate and 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 0.62 for sodium cyanurate,

 

- a high water solubility which is 2000 mg/L at 25 ºC for cyanuric acid and 22300 mg/L at 25 ºC for sodium cyanurate and

 

- similar molecular weights which are129.07 for cyanuric acid and 152.08 for sodium 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” (see attachment).

 

Table 1: Data Matrix, Analogue Approach

 

CAS Number		108-80-5	2624-17-1
CHEMICAL NAME		Analogue 1 Cyanuric acid	Sodium cyanurate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 320 - 440°C	Estimated data: 305ºC
Boiling Point		No data	Estimated data: 697.8ºC
Density		Experimental results: 1.75 g/ml	Experimental results: 1.9 g/ml
Vapour Pressure		No data	Estimated data: 1.41E-016 mm Hg at 25ºC
Partition Coefficient (log Kow)		Experimental results: -1.31 at 25°C	Estimated data: 0.62
Water solubility		Experimental results: 2000 mg/L at 25 ºC	Estimated data: 2.234E+004 mg/L at 25ºC
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 biodegradability	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 > 1178 mg/L
Acute Toxicity to Aquatic Invertebrates		Experimental data: 48 h-LC50 > 1000 mg/L	Read-across from Cyanuric acid: 48 h-LC50 > 1178 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)	Experimental data: 72h-EC50 > 100 mg/L 72h-NOEC = 100 mg/L Experimental data: Sodium cyanurate monohydrate   72h-EbC50= 2700 mg/L (biomass) 72h- ErC50 > 5000 mg/L (growth rate) 72h- NOEC = 1250 mg/L (growth rate)
MAMMALIAN TOXICITY
Acute Oral		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 mg/kg bw
Acute Inhalation		Key study: LC50 >5.25mg/L	Read-across from Cyanuric acid: LC50 >6.19mg/L
Acute Dermal		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 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	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: NOAEL ca. 1520 mg/kg bw/day,male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks   NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Genetic Toxicity in vitro	Gene mutation in bacteria	No data	Key study: Sodium cyanurate monohydrate: Negative
	Mammalian gene mutation	No data	Key study: CHO, with and without metabolic activation, genotoxicity negative
	Chromosomal aberration	No data	Key study: Mouse lymphoma L5178Y cells, with and without metabolic activation, genotoxicity negative
Genetic Toxicity in vivo		No data	Key study: Rat bone marrow cytogenetics assay, genotoxicity negative
Carcinogenicity		No data	Key study: Mouse, 104 weeks NOAEL ca. 1520  mg/kg bw/day, male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Reproductive Toxicity		No data	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   Key study: Rabbit, developmental toxicity. NOAEL maternal = 50 mg/kg bw/day NOAEL teratogenicity = 500 mg/kg bw/day Key study: Sodium cyanurate monohydrate: Rat, developmental toxicity: NOAEL maternal = 5000 mg/kg bw/day NOAEL teratogenicity = 5000 mg/kg bw/day

 

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Cyanuric acid is not irritating
The 72h-primary dermal irritation index (PDII) for substance sodium cyanurate is considered to be 0.

Executive summary:

Based on the experimental results obtained with the analogue cyanuric acid (72h-primary dermal irritation index (PDII)= 0) the read-across approach is applied and the 72h-primary dermal irritation index (PDII) for substance sodium cyanurate is considered to be 0 under test conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation

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:

2 (reliable with restrictions)

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 2624-17-1 sodium cyanurate and the results can be extrapolated to sodium cyanurate.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Read-across approach from a study report (using the methods outlined by the OECD Guideline 405) on the analogue CAS nº 108-80-5 cyanuric acid.

GLP compliance:

no

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

0.3

Reversibility:

fully reversible within: 3 days

Based on the experimental results obtained with the analogue cyanuric acid (72h-overall irritation score= 0.3) , the read-across approach is applied and the same result can be extrapolated for substance sodium cyanurate under test conditions.

The analogue cyanuric acid shares the same functional group with the substance CAS nº 2624-17-1 sodium cyanurate and 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 0.62 for sodium cyanurate,

 

- a high water solubility which is 2000 mg/L at 25 ºC for cyanuric acid and 22300 mg/L at 25 ºC for sodium cyanurate and

 

- similar molecular weights which are129.07 for cyanuric acid and 152.08 for sodium 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” (see attachment).

 

Table 1: Data Matrix, Analogue Approach

 

CAS Number		108-80-5	2624-17-1
CHEMICAL NAME		Analogue 1 Cyanuric acid	Sodium cyanurate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 320 - 440°C	Estimated data: 305ºC
Boiling Point		No data	Estimated data: 697.8ºC
Density		Experimental results: 1.75 g/ml	Experimental results: 1.9 g/ml
Vapour Pressure		No data	Estimated data: 1.41E-016 mm Hg at 25ºC
Partition Coefficient (log Kow)		Experimental results: -1.31 at 25°C	Estimated data: 0.62
Water solubility		Experimental results: 2000 mg/L at 25 ºC	Estimated data: 2.234E+004 mg/L at 25ºC
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 biodegradability	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 > 1178 mg/L
Acute Toxicity to Aquatic Invertebrates		Experimental data: 48 h-LC50 > 1000 mg/L	Read-across from Cyanuric acid: 48 h-LC50 > 1178 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)	Experimental data: 72h-EC50 > 100 mg/L 72h-NOEC = 100 mg/L Experimental data: Sodium cyanurate monohydrate   72h-EbC50= 2700 mg/L (biomass) 72h- ErC50 > 5000 mg/L (growth rate) 72h- NOEC = 1250 mg/L (growth rate)
MAMMALIAN TOXICITY
Acute Oral		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 mg/kg bw
Acute Inhalation		Key study: LC50 >5.25mg/L	Read-across from Cyanuric acid: LC50 >6.19mg/L
Acute Dermal		Key study: LD50 > 5000 mg/kg bw	Read-across from Cyanuric acid: LD50 > 5891 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	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: NOAEL ca. 1520 mg/kg bw/day,male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks   NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Genetic Toxicity in vitro	Gene mutation in bacteria	No data	Key study: Sodium cyanurate monohydrate: Negative
	Mammalian gene mutation	No data	Key study: CHO, with and without metabolic activation, genotoxicity negative
	Chromosomal aberration	No data	Key study: Mouse lymphoma L5178Y cells, with and without metabolic activation, genotoxicity negative
Genetic Toxicity in vivo		No data	Key study: Rat bone marrow cytogenetics assay, genotoxicity negative
Carcinogenicity		No data	Key study: Mouse, 104 weeks NOAEL ca. 1520  mg/kg bw/day, male NOAEL ca. 1580 mg/kg bw/day, female Key study: Sodium cyanurate monohydrate:   Rat, 104 weeks NOAEL ca. 154 mg/kg bw/day, male NOAEL ca. 266 mg/kg bw/day, female
Reproductive Toxicity		No data	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   Key study: Rabbit, developmental toxicity. NOAEL maternal = 50 mg/kg bw/day NOAEL teratogenicity = 500 mg/kg bw/day Key study: Sodium cyanurate monohydrate: Rat, developmental toxicity: NOAEL maternal = 5000 mg/kg bw/day NOAEL teratogenicity = 5000 mg/kg bw/day

 

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Cyanuric acid is not irritating to eyes
The 72h-overall irritation score for substance sodium cyanurate is calculated to be 0.4.

Executive summary:

Based on the experimental results obtained with the analogue cyanuric acid (72h-overall irritation score= 0.3) the read-across approach is applied and the 72h-overall irritation score for substance sodium cyanurate is calculated to be 0.4 under test conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read-across:

1. Based on the experimental results obtained with the analogue cyanuric acid (72h-primary dermal irritation index (PDII)= 0) , the read-across approach is applied and the 72h-primary dermal irritation index (PDII) for substance sodium cyanurate is calculated to be 0 (skin irritation).

2. Based on the experimental results obtained with the analogue cyanuric acid (72h-overall irritation score= 0.3) , the read-across approach is applied and the same result can be extrapolated for substance sodium cyanurate (eye irritation).

Justification for selection of skin irritation / corrosion endpoint:
Read-across approach. Study not performed to GLP and no guideline stated but meets the basic requirements of a guideline study (Klimisch 2).

Justification for selection of eye irritation endpoint:
Read-across approach. Study not performed to GLP and no guideline stated but meets the basic requirements of a guideline study (Klimisch 2).

Justification for classification or non-classification

In the in vivo skin and eye irritation studies cyanuric acid was non-irritant and therefore requires no classification under DSD or CLP. The same results can be extrapolated to sodium cyanurate.