Tetrasodium enneatitanium icosaoxide hydrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20.4.2015-4.5.2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The test was performed according to recommended test Guidelines (OECD Guideline for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008) and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted 24.2.1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(EC) No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The certificate is as an attachment to the study report

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

nonatitanium(4+) tetrasodium hydrate icosaoxidandiide

EC Number:

601-472-6

Cas Number:

117314-20-2

Molecular formula:

Sodium form: Na4Ti9O20 × n H2O Sodium/hydrogen form: 50 % Na4Ti9O20 × n H2O, 50 % Na2H2Ti9O20 × n H2O

IUPAC Name:

nonatitanium(4+) tetrasodium hydrate icosaoxidandiide

Test material form:

solid: particulate/powder

Remarks:

powder

Details on test material:

- Substance type: commercial product (pure active substance)
- Physical state: Solid powder
- Storage condition of test material: Ambient temperature, humidity and pressure. Stored in sealed containers in darkness.
- Stability under test conditions: Stable
- Purity: ca 100 %
- Particle size distribution: 2.92% <100μm
- Crystal structure: TiO6-octaedra
- Density: 2.83 x 10^3 kg/m3
- pH value: the pH value of the substance in an aqueous solution is appr. 11

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: 8 to 12 weeks
- Weight at study initiation: males 251 - 274 g, females 208-224 g
- Fasting period before study: No
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Remarks:

arachis oil BP,

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flanks
- % coverage: 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): After the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): The test item was moistened with Arachis oil BP

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females and 5 males

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 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, mortality

Statistics:

Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioral and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:

Five female and five male rats were treated with 2000 mg/kq bw test item moistened with Arachis Oil BP. The treatment lasted 24 h. The observation period was 14 days.

There were no deaths, signs of systemic toxicity or dermal irritation.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths (see Table 1, Any other infromation on results incl. tables).

Clinical signs:

other: There were no signs of systemic toxicity (see Table 1, Any other infromation on results incl. tables).

Gross pathology:

No abnormalities were noted at necropsy (see Table 3, Any other infromation on results incl. tables).

Other findings:

Dermal Reactions:
Very slight erythema and very slight edema were observed on days three and four in one female. There were no signs of dermal irritation in the remaining animals (see Tables 4 and 5, Any other infromation on results incl. tables).

Any other information on results incl. tables

Table 1 Individual Clinical Observations and Mortality Data

Dose level (mg/kg)	Animal number	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
	and sex	0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -1 M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -2 M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -3 M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 4 M	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 0 F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 1 F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 2 F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 3 F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 4 F	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 2 Individual Body Weights and Body Weight Changes

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Weight Change (g) During Week
		0	7	14	1	2
2000	1-0 Male	263	279	304	16	25
	1-1 Male	274	293	326	19	33
	1-2 Male	255	273	293	18	20
	1-3 Male	264	282	309	18	27
	1-4 Male	251	258	281	7	23
	2-0 Female	224	227	232	3	5
	2-1 Female	213	213	216	0	3
	2-2 Female	212	207	213	-5	6
	2-3 Female	211	210	215	-1	5
	2-4 Female	208	207	217	-1	10

Table 3 Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Male	Killed Day 14	No abnormalities detected
	1-1 Male	Killed Day 14	No abnormalities detected
	1-2 Male	Killed Day 14	No abnormalities detected
	1-3 Male	Killed Day 14	No abnormalities detected
	1-4 Male	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Killed Day 14	No abnormalities detected
	2-4 Female	Killed Day 14	No abnormalities detected

Table 4 Individual Dermal Reactions - Males

Dose level (mg/kg)	Animal number	Observation			Effects Noted After Initiation of Exposure (Days)
	and sex		1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 1 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 2 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 3 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 - 4 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 5 Individual Dermal Reactions - Females

Dose level (mg/kg)	Animal number	Observation			Effects Noted After Initiation of Exposure (Days)
	and sex		1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 F	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 1 F	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 2 F	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 3 F	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 - 4 F	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
		Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

According to GHS, the substance is unclassified.

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 body weight. Therefore the test item is not classified as acutely toxic via the skin.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Very slight erythema and very slight edema were observed on days three and four in one female. There were no signs of dermal irritation in the remaining animals.

Body Weight. Four females showed body weight loss or no gain in body weight during the first week with expected gain in body weight during the second week. The remaining animals showed expected gains in body weight over the study period.

Necropsy. No abnormalities were noted at necropsy.

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 body weight.