Tetrasodium enneatitanium icosaoxide hydrate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

In accordance with column 2 of REACH Annex VIII, the most appropriate route of administration should be selected for the short-term repeated dose toxicity study (required in section 8.6.1). In the acute dermal toxicity studies for the substance there were only very slight erythema and very slight edema in one animal, and no other signs of dermal irritation or of systemic toxicity. No severe adverse effects were observed. The substance is not classified as acutely toxic via the skin. The results from the skin sensitisation, corrosion and irritation studies were negative.

The molecular mass of the substance (> 800 g/mol) does not promote skin penetration, and besides a basic pH of 11 – 11.2 in aqueous solution, there are no other relevant physico-chemical properties that would suggest potential for a significant rate of absorption through the skin. The substance is very stable, inorganic and insoluble. The dermal route of exposure is therefore not deemed most appropriate for the substance. Instead, the study is performed for the oral route and documented in the IUCLID endpoint 7.5.1.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted 24.2.1987

Deviations:

no

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

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

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.

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.

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).

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

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.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Skin irritation/corrosion: 
Skin corrosion study (in vitro, occlusive, 3 and 60 minutes), human (EPIDERM™ Human Skin Model) - GLP, OECD Guideline 431: non-corrosive to skin (relative mean tissue viability 3 min: 94.9% and 60 min: 99.6%)
Acute (single dose) eye irritation study (in vivo), rabbit (New Zealand White) - GLP, OECD Guideline 405, EU Method B5: eye irritant (category 2, H319) (overall irritation score: 12.5) 

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

There are no data gaps in irritation/corrosion. Even though there is no human data available on the hazards of the substance for eye irritation, there is no reason to believe that the observed results in the acute eye irritation study in the New Zealand White strain rabbit would not be relevant to humans. Skin corrosion and skin irritation are studied on human skin and epidermis models.

No adverse effects severe enough to cause classification of the test item were observed in either the skin corrosion study or the skin irriation study. However, in the acute eye irritation study, the test item produced a maximum group mean score of 12.5 and was classified as an eye irritant (category 2, H319) according to the CLP Regulation (EC No 1272/2008).

Justification for selection of skin irritation / corrosion endpoint:
The in vitro skin corrosion study was chosen over the in vitro skin irritation study, as it featured a higher amount of the test item applied and two different exposure times investigated, and gave more varied results in terms of relative mean viabilities of the test item treated tissues. In both studies no adverse effects were observed.

Justification for selection of eye irritation endpoint:
The in vivo acute eye irritation study was chosen over the in vitro eye irritation study because the results of the in vivo study are sufficient to make conclusions related to the test items eye irritation effects. The results of the in vitro study have identified the test item as not causing serious eye damage, but they do not permit conclusion that the test item does not require classification for eye irritation.

Effects on eye irritation: irritating

The test item is not classified as irritant or corrosive to the skin, but is classified as an eye irritant (category 2, H319).

Skin corrosion: the test item was considered to be non-corrosive to the skin, as it did not turn the MTT solution blue and the OD562 values were well above the limits for the prediction levels. The test item was also classified as non-irritant with regards to skin irritation.

Eye irritation: the test item produced a maximum group mean score of 12.5 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. According to the CLP Regulation (EC No 1272/2008) the results indicate that the test item is an eye irritant (category 2, H319).

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11.11.2014 - 25.11.2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was performed according to the recommended Guidelines (OECD Guideline for the Testing of Chemicals No. 429 "Skin Sensitization: Local Lymph Node Assay" (adopted 22 July 2010) and Method B42 Skin Sensitization (Local Lymph Node Assay) of Commission Regulation (EC) No. 440/2008) and GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

Adopted 22 July 2010

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

(EC) No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate is as an attachement to the study report

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

The substance has a low vapour pressure and is insoluble in water.
The substance is stable under test conditions.

Species:

mouse

Strain:

CBA

Remarks:

CBA/Ca (CBA/CaOlaHsd)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 15 - 23 g
- Housing: The animals were individually housed in suspended solid floor polypropylene cages furnished with softwood woodflakes. Free access to mains tap water and food was allowed throughout the study.
- 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 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

propylene glycol

Concentration:

Test item at concentrations 10 %, 5 % and 2.5 % w/w in propylene glycol.

No. of animals per dose:

Four

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: Non-soluble
- Irritation: Non-irritant. No signs of visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted.
- Systemic toxicity: No signs of systemic toxicity were noted
- Lymph node proliferation response: overall mean ear thickness change (%): -2.33

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay in the Mouse
- Criteria used to consider a positive response:
The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non-sensitizer

TREATMENT PREPARATION AND ADMINISTRATION:
For the purpose of the study, the test item was freshly prepared as a suspension in propylene glycol. This vehicle was chosen as it produced the highest concentration that was suitable for dosing.

The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Groups of four mice were treated with the test item at concentrations of 10%, 5% or 2.5% w/w in propylene glycol. The preliminary screening test suggested that the test item would not produce systemic toxicity or excessive local skin irritation at the highest suitable concentration. The mice were treated by daily application of 25 μL of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette. No patch was used.

A further group of four mice received the vehicle alone in the same manner.

Five days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 250 μL of phosphate buffered saline (PBS) containing 3H-methylthymidine (3HTdR: 80 μCi/mL, specific activity 2.0 Ci/mmoL, ARC UK Ltd) giving a total of 20 μCi to each mouse.

Positive control substance(s):

other: Phenylacetaldehyde (>90%)

Statistics:

The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index). The Stimulation Index is expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group.

Positive control results:

The positive control study was performed according to the OECD Guideline for the Testing of Chemicals No. 429 "Skin Sensitisation: Local Lymph Node Assay" (adopted 22 July 2010) and Method B42 Skin Sensitisation (Local Lymph Node Assay) of Commission Regulation (EC) 440/2008.

Three groups, each of five animals, were treated with 50 μL (25 μL per ear) of Phenylacetaldehyde (>90%) as a solution in propylene glycol at concentrations of 2.5%, 5% or 10% v/v. A further group of five animals was treated with propylene glycol alone.

Phenylacetaldehyde (>90%) was considered to be a sensitizer under the conditions of the test, based on the stimulation index results.

The laboratory has further historical data on positive controls.

Key result

Parameter:

SI

Value:

0.93

Test group / Remarks:

Concentration of test item: 10 % w/w in propylene glycol

Remarks on result:

other: Negative for skin sensitisation

Remarks:

Average SI value for the 10 % dose group

Parameter:

SI

Value:

1.36

Test group / Remarks:

Concentration of test item: 5 % w/w in propylene glycol

Remarks on result:

other: Negative for skin sensitisation

Remarks:

Average SI value for the 5 % dose group

Parameter:

SI

Value:

1.42

Test group / Remarks:

Concentration of test item: 2.5 % w/w in propylene glycol

Remarks on result:

other: Negative for skin sensitisation

Remarks:

Average SI value for the 2.5 % dose group

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
For the radioactive disintegrations per minute per lymph node and the stimulation index, see Table 1, Any other information on results incl. tables.

The proliferation response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node).

DETAILS ON STIMULATION INDEX CALCULATION
The proliferation response of lymph node cells is also expressed as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in 3HTdR incorporation will be classified as a "non-sensitizer."

EC3 CALCULATION
For the positive control, the concentration of Phenylacetaldehyde (>90%) expected to cause a 3 fold increase in 3HTdR incorporation (EC3 value) was calculated to be 4%.

CLINICAL OBSERVATIONS:
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.

BODY WEIGHTS
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period (see Table 2, Any other information on results incl. tables).

Table 1. Average Disintegrations per Minute, Disintegrations per Minute/Node and Stimulation Index.

Concentration (% w/w) in propylene glycol	dpm	dpm/Node	Stimulation Index	Result
Vehicle	9858.23	1232.28	na	na
2.5	14000.02	1750.00	1.42	Negative
5	13388.71	1673.59	1.36	Negative
10	9215.09	1151.89	0.93	Negative

dpm = Disintegrations per minute

a = Disintegrations per minute/node obtained by dividing the disintegrations per minute value by 8 (total number of lymph nodes)

b = Stimulation Index of 3.0 or greater indicates a positive result

na = Not applicable

Table 2. Individual Body Weights and Body Weight Change

Concentration (% w/w) in propylene glycol	Animal Number	Body Weight (g)		Body Weight Change (g)
		Day 1	Day 6
Vehicle	1-1	17.9	19.1	1.2
	1-2	23.1	23.0	-0.1
	1-3	18.3	19.7	1.4
	1-4	19.1	20.3	1.2
2.5	2-1	19.4	18.8	-0.6
	2-2	15.6	16.3	0.7
	2-3	20.8	19.9	-0.9
	2-4	21.6	20.3	-1.3
5	3-1	19.7	18.5	-1.2
	3-2	20.0	21.7	1.7
	3-3	22.0	22.1	0.1
	3-4	18.6	19.8	1.2
10	4-1	18.2	18.0	-0.2
	4-2	18.5	18.8	0.3
	4-3	18.5	19.1	0.6
	4-4	23.1	22.6	-0.5

Interpretation of results:

GHS criteria not met

Remarks:

The test item was considered to be a non-sensitizer under the conditions of the test. Criteria used for interpretation of results: EU

Conclusions:

There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.

Based on these observations and the Stimulation Index at different tested concentrations, the results were negative for sensitization. The test item was considered to be a non-sensitizer under the conditions of the test. It is therefore not classified as sensitizing according to the CLP Regulation.

Executive summary:

Introduction

A study was performed to assess the skin sensitization potential of the test item in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear.

Methods

Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 10% w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of four animals, were treated with 50 μL (25 μL per ear) of the test item as a suspension in propylene glycol at concentrations of 10%, 5% or 2.5% w/w. A further group of four animals was treated with propylene glycol alone.

Results

The Stimulation Index was expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group. For all of the tested concentrations of the test item, the result according to the Stimulation Index was negative.

Conclusions

The test item was considered to be an non-sensitizer under the conditions of the test.

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified