Disodium phthalate

Acute Toxicity: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Disodium phthalate

EC Number:

240-106-6

EC Name:

Disodium phthalate

Cas Number:

15968-01-1

Molecular formula:

C8H6O4.2Na

IUPAC Name:

disodium phthalate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Phthalic acid sodium salt (disodium phthalate)
- Physical state: white powder
- Analytical purity: > 95%
- Storage condition of test material: room temperature in the dark

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

 Table 1:    Summary of acute dermal toxicity

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

Applicant's summary and conclusion

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.