Reaction mass of iron chelate of sodium salt N-[1,2 dicarboxyethyl] D,L aspartic acid and sodium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May, 29 - June, 12, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Statement of GLP Compliance No G-024 issued by Slovac National Accreditation Service; Statement of GLP Compliance No 4/2006/DPL issued by Bureau for Chemical Substances and Preparations

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

666828-40-6

Cas Number:

666828-40-6

IUPAC Name:

666828-40-6

Constituent 2

Reference substance name:

Fe(III)IDHA

IUPAC Name:

Fe(III)IDHA

Test material form:

other: microgranules

Details on test material:

- Name of test material (as cited in study report): Fe(III)IDHA
- Substance type: chelate
- Physical state: green microgranules

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Institute of Occupational Medicine in Łódz kept in conventional type.
- Age at study initiation: 10-week-old male rats and 11-weekold females
- Weight at study initiation: male rats with the average body weight of 287 g and females with the average body weight of 194 g
- Fasting period before study: no
- Housing:
- Diet (e.g. ad libitum): standard granulated "Murigran" fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz
- Water (e.g. ad libitum): tap water
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23 °C;
- Humidity (%): 48 - 80
- Photoperiod (hrs dark / hrs light): artificial, fluorescent lighting: 12 hours light / 12 hours darkness

The animals were kept in cages with plastic bottom and wired lid, with dimensions: (length x width x height) 58 x 37 x 21 cm. Following administration of the test material on animals skin, each one was kept individually per cage. After removal of the test material from animals skin, during the following days of experiment the rats were kept five per cage, each sex separately.

Wooden UV-sterilized shavings were used as a litter. Each cage was equipped with label containing information on name of test material, study code, used dose, start date and planned ending date of the experiment, animal sex and animal numbers.

IN-LIFE DATES: From: To:
The experiment was started on May 29th, 2007 (males and females) and ended on June 12th, 2007.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The day before the test back and sides of animals were shaved with electric razor on skin surface area of about 4 x 6 cm. Only those animals that showed no macroscopically visible irritation or damages of skin were used for the experiments. The animals were not starved prior to the experiment.

The undiluted test material was applied to the dorsal skin of 10 rats (5 males and 5 females) in dose of 2000 mg/kg b.w. The area of skin treated with the test material was about 6 cm2. The test material was applied to gauze patches and then laid on the prepared skin. The gauze patches were covered with PCV foil and elastic bandage was used to make circular protecting band. After 24 hours the band and gauze patches were taken off and the residual test material was removed using water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Evaluation of general condition of animals, i.e. observation of all animals in regards to mortality and morbidity was conducted twice a day during 14-day observation period. Following administration of the test material, detailed clinical observations were performed in hour intervals during the day of administration (day 0). Since the first till the 14th day of observation period detailed clinical observations were performed once a day.
Body weight of animals was determined individually for each animal directly before administration of the test material (day 0) and then on seventh andfourteenth day - before the finishing of the experiment.
- Necropsy of survivors performed: yes
- Other examinations performed: After opening of thorax and abdomen macroscopic examination of internal organs was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All rats survived the 14-day observation period.

Clinical signs:

other: During 14-day experiment period no changes on skin or in behavior of test animals were stated.

Gross pathology:

No pathological changes were stated in animals during macroscopic examination.

Any other information on results incl. tables

Chelate with name: Fe (III) IDHA Acute dermal toxicity study for rats – clinical signs – overall list

Dose (mg/kg b.w.)	Sex	Day after administration	No of alive animals	Rat No
				1	2	3	4	5
2000	Males	0	5	NC	NC	NC	NC	NC
		1	5	NC	NC	NC	NC	NC
		2	5	NC	NC	NC	NC	NC
		3	5	NC	NC	NC	NC	NC
		4	5	NC	NC	NC	NC	NC
		5	5	NC	NC	NC	NC	NC
		6	5	NC	NC	NC	NC	NC
		7	5	NC	NC	NC	NC	NC
		8	5	NC	NC	NC	NC	NC
		9	5	NC	NC	NC	NC	NC
		10	5	NC	NC	NC	NC	NC
		11	5	NC	NC	NC	NC	NC
		12	5	NC	NC	NC	NC	NC
		13	5	NC	NC	NC	NC	NC
		14	5	NC	NC	NC	NC	NC
	Females	0	5	NC	NC	NC	NC	NC
		1	5	NC	NC	NC	NC	NC
		2	5	NC	NC	NC	NC	NC
		3	5	NC	NC	NC	NC	NC
		4	5	NC	NC	NC	NC	NC
		5	5	NC	NC	NC	NC	NC
		6	5	NC	NC	NC	NC	NC
		7	5	NC	NC	NC	NC	NC
		8	5	NC	NC	NC	NC	NC
		9	5	NC	NC	NC	NC	NC
		10	5	NC	NC	NC	NC	NC
		11	5	NC	NC	NC	NC	NC
		12	5	NC	NC	NC	NC	NC
		13	5	NC	NC	NC	NC	NC
		14	5	NC	NC	NC	NC	NC

NC – no changes

Chelate with name: Fe (III) IDHA Acute dermal toxicity study for rats – body weight of animals (g)

Dose (mg/kg b.w.)	Sex	Rat No	Day			Difference
			0	7	14	14 - 0
2000	Males	1	260	281	302	42
		2	299	308	326	27
		3	285	293	315	30
		4	300	316	345	45
		5	293	309	332	39
		1	191	206	209	18
	Females
		2	191	203	215	24
		3	194	203	211	17
		4	198	207	216	18
		5	195	199	218	23

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Taking into account the obtained results one may state that the median dermal acute dose (LD50) for Chelate with name: Fe (III) IDHA is higher than 2000 mg/kg b.w.

Executive summary:

Acute dermal toxicity study of Chelate with name: Fe (III) IDHA for rats was performed according to the OECD Guideline for Testing of Chemicals No 402/ Method B.3 as well as Principles of Good Laboratory Practice (GLP - OECD, 1997). The test material was given to 10 rats (5 males and 5 females) to shaved dorsal skin in single dose of 2000 mg/kg b.w. for 24 hours. During 14-day observation period no changes on skin or in behavior were stated in test animals. All animals survived 14- day experiment period. All animals which were euthanized after 14-day observation period were dissected and studied macroscopically. Macroscopic examination showed no pathological changes in test animals. Taking into account the obtained results one may state that median dermal acute dose (LD50) for Chelate with name: Fe (III) IDHA is higher than 2000 mg/kg b.w.