Disodium phthalate

Endpoint summary

Description of key information

Key study: Acute oral: Read-across from experimental results on an analogue: Similar to OECD guideline 401. No GLP data.
LD50 = 3200 mg/kg bw
 
Key study: Acute dermal: Experimental results: OECD guideline 402 and EU method B.3. GLP study.
LD50 > 2000 mg/kg bw
 
Acute inhalation: Data waiving: In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute 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:

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 88-99-3 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:

not specified

Test type:

standard acute method

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 200 mg/kg bw

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 88-99-3 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		88-99-3	15968-01-1
CHEMICAL NAME		Analogue Phthalic acid	Target chemical Disodium phthalate
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 230 ºC	Experimental results: No evidence of melting point below 400 ºC. Decompositionin the range of 450 to 500 °C.
Boiling Point		Experimental results: Decomposes	No determination of boiling point is required since there was no evidence of melting below 400 ºC.
Density		Experimental results: 1.593 g/cm3 at 15 ºC	Experimental results: 1.67 at 20.8 ºC
Vapour Pressure		Experimental results: 8.48 x 10-5 Pa at 25 ºC	Experimental results: < 3.9 x 10 -5 Pa at 25 ºC
Partition Coefficient (log Kow)		Experimental results: 0.73	Experimental results: -2.34 at 20.1 ºC (pH 5.5)
Water solubility		Experimental results: 6250-7010 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		Estimated data: Readily biodegradable (BIOWIN v4.10)	Estimated data: Readily biodegradable (BIOWIN v4.10)
Anaerobic Biodegradation		No data	No data
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		No data	No data
Acute Toxicity to Aquatic Invertebrates		No data	No data
Toxicity to Aquatic Plants		No data	No data
MAMMALIAN TOXICITY
Acute Oral		Experimental results: LD50 = 2530 mg/kg (mouse)	Read-across: LD50 = 3200 mg/kg (mouse)
Acute Inhalation		No data	No data
Acute Dermal		No data	Experimental results: LD50 > 2000 mg/kg
Skin irritation / Eye irritation		No data	Experimental results: Not a skin irritant. Not an eye irritant.
Skin sensitisation		No data	Experimental results: Non-sensitising.
Repeated Dose		No data	No data
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	No data	Experimental results: Negative
Genetic Toxicity in vivo		Experimental results: Negative	Read-across: Negative
Carcinogenicity		No data	No data
Reproductive Toxicity: developmental toxicity		Developmental toxicity: No evidence of developmental toxicity. NOAEL, maternal toxicity= 1021 mg/kg bw/day; NOAEL, developmental toxicity= 1763 mg/kg bw/day	Read-across: No evidence of developmental toxicity. NOAEL, maternal toxicity= 1291 mg/kg bw/day; NOAEL, developmental toxicity= 2230 mg/kg bw/day

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on experimental data, the read-across approach is applied and the LD50 for the substance is 3200 mg/kg bw.

Executive summary:

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 88-99-3 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the LD50 for the substance is 3200 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 200 mg/kg bw

Quality of whole database:

Read-across approach. Klimisch 2.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 7 November 2012 to 28 November 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline and EU method. GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: eight to twelve weeks of age.
- Weight at study initiation: males: 233-320 g; females: 210-225 g
- Fasting period before study: No.
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet, ad libitum.
- Water (e.g. ad libitum): drinking water, ad libitum.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Type of coverage:

semiocclusive

Vehicle:

other: moistened with distilled water

Details on dermal exposure:

TEST SITE
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.
- Time after start of exposure: 24 h

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes. All animals were subjected to gross necropsy. This consisted of an external examination and opening of
the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.
- Other examinations performed: After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

A cavity in the right kidney, right and left kidney and/or hydronephrosis, which were considered to be a genetic defect and not test item related, was noted at necropsy of two males. No abnormalities were noted at necropsy of the remaining animals.

Other findings:

There were no signs of dermal irritation.

 Table 1:    Summary of acute dermal toxicity

	Males	Females
Dose	Mortality	Mortality
2000 mg/kg bw	0/5	0/5

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the OECD Guideline No. 402 “Acute Dermal Toxicity” and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008. Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. There were no signs of systemic toxicity. There were no signs of dermal irritation. One female showed no bodyweight gain during the first week but expected gain in bodyweight during the second week. One other female showed expected gain in bodyweight during the first week but no bodyweight gain during the second week. Remaining animals showed expected gains in bodyweight over the study period. A cavity in the right kidney, right and left kidney and/or hydronephrosis, which were considered to be a genetic defect and not test item related, was noted at necropsy of two males. No abnormalities were noted at necropsy of the remaining animals. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Additional information

Key study: Acute oral: Read-across from experimental results on an analogue: Similar to OECD guideline 401. No GLP data.

LD50 = 3200 mg/kg bw

 

Key study: Acute dermal: Experimental results: OECD guideline 402 and EU method B.3. GLP study.

LD50 > 2000 mg/kg bw

 

Acute inhalation: Data waiving: In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – oral endpoint
Data from two publications are available for the analogue. The lowest LD50 value is considered as the key study.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

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

Oral LD50 > 2000 mg/kg bw: not classified.

Dermal LD50 >2000 mg/kg bw: not classified.