Poly(polyalkylammonium) poly(µ-alkoxy)-µ6-oxido-polyhedropoly(chloridometal)ate polyalkanol solvate

Endpoint summary

Description of key information

The substance was tested for acute dermal irritation/corrosion properties in rabbits (patch test), according to OECD guideline 404, EC method B.4.and OCSPP guideline 870.2500.

Under the present test conditions, none of the three male rabbits exposed for 4 hours to 500 mg test item/patch (semi-occlusive conditions) showed any skin reaction. There were no systemic intolerance reactions. Therefore, the test substance was non-irritating to skin, hence no labelling is required (LPT 2013).

 

An eye irritation test according to OECD guideline 405 was performed on rabbit eyes (irritation/corrosion test).

Under the present test conditions a single administration of 100 mg test item per animal into the conjunctival sac of the right eye of three rabbits caused irritating effects (LPT 2013).

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-09-19 to 2012-11-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; GLP study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS: 
- Source: LPT, Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: female
- Age: approx. 14.5 - 20.5 months
- Weight at study initiation: 2.7 kg to 3.2 kg
- Housing: single
- Diet: ad libitum, ssniff K-H (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: untreated skin surrounding the application area
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mg test item/patch and animal

Duration of treatment / exposure:

4 hour(s)

Observation period:

Postexposure period: 72 hours (Because no effects have been observed the period of observation is not 14 days but 72 hours.)

Number of animals:

3

Details on study design:

ADMINISTRATION/EXPOSURE
- Preparation of test substance: 1000 mg of the test item were mixed with 0.5 mL aqua ad iniectabilia,
750 mg of this paste were applied per animal (= 500 mg test item/animal)
- Area of exposure: dorsal area of trunk, shaved 24 hours in advance,  approx. 6 cm2
- Concentration: 0.5 mg of the test item was applied to the test site (area: approx. 6 cm2).
- Occlusion: gauze patch held in place by semi-occlusive non-irritating  tape dressing
- Washing: at the end of the exposure time no residual test item had to be removed.
- Inital test: As there was no evidence of the test item producing severe irritancy or corrosion by the test item, a single patch was applied to one
animal for 4 hours.
- Confirmatory test: As no corrosive or severe irritant effects were observed in the initial test, 2 further animals were employed 24 hours after start
of the initial test.
EXAMINATIONS
- Examination time points: 60 minutes, 24, 48, 72 hours,
- Scoring system: Draize (0-4 possible scores each for erythema/eschar  and for edema)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

AVERAGE SCORE
- Erythema: 0
- Edema: 0

Other effects:

no other effects

Findings                                Examination                  Skin irritation scores

of the skin                            schedule                      

animal no.

1             2            3

E/Oe          E/Oe        E/Oe

          500 ml substance/patch/animal

 

erythema and

eschar formations/                           before dosing              0/0          0/0        0/0

oedema formation

time after removal

of the patch

(4-hour exposure)

60 min                          0/0            0/0          0/0

24 hours                       0/0            0/0          0/0

48 hours                     0/0            0/0          0/0

72 hours                    0/0            0/0          0/0

 

0   no pathological findings    

E   erythema and eschar formations 

Oe  oedema

Conclusions:

Under the present test conditions, none of the three female rabbits exposed for 4 hours to 500 mg test item/patch (semi-occlusive conditions)
showed any skin reaction. There were no systemic intolerance reactions. Therefore, the test item was non-irritating to skin, hence no labelling is
required.

Executive summary:

The purpose of this study was to examine the test substance for acute dermal irritation/corrosion properties in rabbits (patch test), according to OECD guideline 404, EC method B.4.and OCSPP guideline 870.2500.

Under the present test conditions, none of the three male rabbits exposed for 4 hours to 500 mg test item/patch (semi-occlusive conditions) showed any skin reaction. There were no systemic intolerance reactions. Therefore, the test substance was non-irritating to skin, hence no labelling is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-09-19 to 2012-11-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; GLP study without deviation

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

GLP compliance:

yes

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: 
- Source: LPT, Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: male
- Age: approx. 7 to 9 months
- Weight at study initiation: 2.4 kg up to 3.1 kg
- Housing: single
- Diet: ad libitum, ssniff K-H (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: identical animal, second eye
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: identical animal, left eye

Amount / concentration applied:

Amount: 100 mg of the fine mortared test item were administered per eye and tested in three animals.

Duration of treatment / exposure:

Single instillation into the conjunctival sac of the right eye. One hour after administration the eyes were rinsed with 20 mL 0.9% aqueous
NaCl solution.

Observation period (in vivo):

1, 24, 48, 72 hours and 4 to 15 days after the administration

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

ADMINISTRATION: The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further
animals were employed 24 hours after start of the initial test.
100 mg of the fine mortared test item were administered per eye and tested in three animals.
The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

REMOVAL OF TEST SUBSTANCE
- Washing: One hour after administration the eyes were rinsed with 20 mL 0.9% aqueous NaCl solution.
TOOL USED TO ASSESS SCORE: The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 15 days after the administration. The eye reactions were observed and registered.
24 hours, 7 and 14 days after administration the eyes were treated additionally with fluorescein3 and examined. The eye reactions were observed
and registered.

SCORING SYSTEM: Draize scale

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 11 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

AVERAGE SCORE
- Cornea: 0.67
- Iris: 0
- Conjunctivae (Redness): 1.0
- Conjunctivae (Chemosis): 2.0

Other effects:

There were no systemic intolerance reactions.

Acute eye irritation/corrosion test of the test item

 

Examination of the treated eye

Time after administration	C O R N E A	I R I S	C O N J U N C T I V A E
	Opacity		Redness^#	Chemosis^##
	A n i m a l n o. : 1 / 2 / 3
right eye: 100 ml test item
before dosing	0/0/0	0/0/0	0/0/0	0/0/0
1 hour	0/0/0	0/0/0	1/1/1	2/1/1
24 hours	1/1/0	0/0/0	1/1/1	4/2/2
48 hours	1/1/0	0/0/0	1/1/1	3/2/1
72 hours	1/1/0	0/0/0	1/1/1	2/1/1

# refers to palpebral and bulbar conjunctivae; excluding cornea and iris

## Swelling: refers to lids and/or nictitating membrane

24 hours fluorescein test: all animals: corneal staining (up to 1/4 of the surface)

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

According to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures,
the test item is i r r i t a t i n g to eyes (labelling requirement: H319).

Executive summary:

The purpose of this study was to obtain information on the influence of the test item on rabbit eyes (irritation/corrosion test), according to OECD guideline 405, EC method B.5. and OCSPP guideline 870.2400.

 

Under the present test conditions a single administration of 100 mg test item per animal into the conjunctival sac of the right eye of three rabbits caused following effect:

Corneal opacity (grade 1) was observed in animal no. one 24 hours to 10 days and in animal no. two 24 hours to 14 days after instillation.

The fluorescein tests performed 24 hours and 7 days after instillation revealed corneal staining in all animals (up to 1/4 of the surface).

Conjunctival redness (grade 1) was observed in all animals 1 hour to 7 days, in animal no. 1 until 9 days and in animal no. 3 until 10 days after instillation.

Chemosis was observed in all animals:

- animal no. 1: 24 hours (grade 4), 48 hours (grade 3), 1 hour and 72 hours to 5 days (grade 2) and 6 days (grade 1) after instillation;

- animal no. 2: 24 and 48 hours (grade 2), 1 hour and 72 hours to 5 days (grade 1) after instillation;

- animal no. 3: 24 hours (grade 2), 1 hour, 48 and 72 hours (grade 1) after instillation.

The irises were not affected by instillation of the test item.

There were no systemic intolerance reactions.

According to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, the test item is i r r i t a t i n g to eyes..

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, the test item is not irritating to the skin but irritating to eyes (Eye Irrit. Cat.2)