Disodium phthalate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

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: see 'Remark'

Remarks:

On contact with water, the substance CAS 85-44-9 (phthalic anhydride) is rapidly hydrolyzed to phthalic acid. The substance CAS 15968-01-1 (disodium phthalate) is the sodium salt of the phthalic acid CAS 88-99-3. The main assumption is that sodium is not significant in respect of all the properties under consideration. In dilute aqueous conditions of defined pH a salt will behave no differently to the parent acid, at identical concentration of the particular speciated form present and will be fully dissociated. Therefore, the results obtained with the substance CAS 85-44-9 can be used for the read-across approach.

Principles of method if other than guideline:

Read-across approach from data on an analogue.

GLP compliance:

no

Dose descriptor:

NOAEL

Effect level:

709 mg/kg bw/day (nominal)

Sex:

male/female

Critical effects observed:

not specified

On contact with water, the substance CAS 85-44-9 (phthalic anhydride) is rapidly hydrolyzed to phthalic acid. The substance CAS 15968-01-1 (disodium phthalate) is the sodium salt of the phthalic acid CAS 88-99-3. The main assumption is that sodium is not significant in respect of all the properties under consideration. Therefore, the results obtained with the substance CAS 85 -44 -9 can be used for the read-across approach.

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		85-44-9	15968-01-1
CHEMICAL NAME		Analogue Phthalic anhydride	Target chemical Disodium phthalate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 130.8 ºC	Experimental results: No evidence of melting point below 400 ºC. Decompositionin the range of 450 to 500 °C.
Boiling Point		Experimental results: 295 ºC	No determination of boiling point is required since there was no evidence of melting below 400 ºC.
Density		Experimental results: 1.20 at 135 ºC (liquid); 1.53 at 20 ºC (solid)	Experimental results: 1.67 at 20.8 ºC
Vapour Pressure		Experimental results: 0.07 Pa at 25 ºC	Experimental results: < 3.9 x 10 -5 Pa at 25 ºC
Partition Coefficient (log Kow)		Experimental results: 1.6	Experimental results: -2.34 at 20.1 ºC (pH 5.5)
Water solubility		Experimental results: 6000-6200 mg/L at 25 ºC	Experimental results: In the range of 45.8 to 47.9% w/w at 20 ºC.
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Experimental results: Readily biodegradable	Estimated data: Readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Experimental results: LC50 (96 h) > 99 mg/L	Read-across: LC50 (96 h) > 140 mg/L
Acute Toxicity to Aquatic Invertebrates		Experimental results: EC50 (48 h) = 71 mg/L	Read-across: EC50 (48 h) = 100 mg/L
Chronic (Reproduction) Toxicity to Aquatic Invertebrates		Experimental results: NOEC (21 d) = 16 mg/L	Read-across: NOEC (21 d) = 23 mg/L
Toxicity to Aquatic Plants		Experimental results: EC50 (72 h) = 68 mg/L (growth rate) 72 -h NOEC =32 mg/L (growth rate)	Read-across: EC50 (72 h) = 96 mg/L (growth rate) 72 -h NOEC = 45 mg/L (growth rate)
MAMMALIAN TOXICITY
Acute Oral		According to the CLP Regulation harmonised classification, the substance is classified as Acute oral toxicity category 4.	No data
Acute Inhalation		No data	No data
Acute Dermal		No data	Experimental results: LD50 > 2000 mg/kg
Skin irritation / Eye irritation		According to the CLP Regulation harmonised classification, the substance is classified as: Skin irritant category 2 Eye damage category 1	Experimental results: Not a skin irritant. Not an eye irritant.
Skin sensitisation		According to the CLP Regulation harmonised classification, the substance is classified as: Skin sensitiser category 1 Respiratory sensitiser category 1	Experimental results: Non-sensitising.
Repeated Dose		Experimental results: NOAEL from chronic study: 500 mg/kg bw/day (male/female)	Read-across: NOAEL from chronic study: 709 mg/kg bw/day (male/female)
Genetic Toxicity in vitro	Gene mutation in bacteria	Experimental results: Negative	Read-across: Negative
	Chromosomal aberration	Experimental results: Negative	Experimental results: Negative
	Mammalian gene mutation	Experimental results: Positive at toxic doses.	Experimental results: Negative
Genetic Toxicity in vivo		No data	No data
Carcinogenicity		Experimental results: Not carcinogenic.	No data
Reproductive Toxicity: developmental toxicity		No data	No data

Conclusions:

Based on experimental data, the read-across approach is applied and the NOAEL for the substance is 709 mg/kg bw/day (chronic data).

Executive summary:

On contact with water, the substance CAS 85-44-9 (phthalic anhydride) is rapidly hydrolyzed to phthalic acid. The substance CAS 15968-01-1 (disodium phthalate) is the sodium salt of the phthalic acid CAS 88-99-3. The main assumption is that sodium is not significant in respect of all the properties under consideration. Therefore, the results obtained with the substance CAS 85-44-9 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for the substance is 709 mg/kg bw/day (chronic data).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

709 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Read-across approach. Klimisch 2.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key study: Read-across approach from an analogue.

On contact with water, the substance CAS 85-44-9 (phthalic anhydride) is rapidly hydrolyzed to phthalic acid. The substance CAS 15968-01-1 (disodium phthalate) is the sodium salt of the phthalic acid CAS 88-99-3. The main assumption is that sodium is not significant in respect of all the properties under consideration. In dilute aqueous conditions of defined pH a salt will behave no differently to the parent acid, at identical concentration of the particular speciated form present and will be fully dissociated. Therefore, the results obtained with the substance CAS 85-44-9 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for the substance is 709 mg/kg bw/day (chronic data).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Chronic data from two published studies (rats and mice) are available for the analogue. The NOAEL value obtained in the study with rats is considered for the effect level. In the study with mice, no NOAEL was established (LOAEL=1717 mg/kg bw/day for females and 2340 mg/kg bw/day for males).

Justification for classification or non-classification

Based on the available data, the substance is not classified for repeated dose toxicity.