Disodium phthalate

Repeated dose toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2012

Materials and methods

Principles of method if other than guideline:

Read-across approach from data on an analogue.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phthalic anhydride

EC Number:

201-607-5

EC Name:

Phthalic anhydride

Cas Number:

85-44-9

IUPAC Name:

2-benzofuran-1,3-dione

Details on test material:

- Molecular formula (if other than submission substance): C8H4O3
- Molecular weight (if other than submission substance): 148.1156
- Smiles notation (if other than submission substance): O=C1OC(=O)c2ccccc12
- InChl (if other than submission substance): InChI=1/C8H4O3/c9-7-5-3-1-2-4-6(5)8(10)11-7/h1-4H
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

709 mg/kg bw/day (nominal)

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).