Magnesium potassium titanium oxide

Endpoint summary

Description of key information

Terracess P  was not irritating to eyes and skin in the appropriate EC/OECD tests.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 October 2000 - 03 November 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Animal: Albino rabbit, New Zealand white (SPF quality). Earmark.
- Source: Charles River Deutschland, Kissleg, Germany
- Age at study initiation: at least 8 weeks old
- Body weight at study initiation: between 1.0 and 3.5 kg
- Housing: individually housed in labelled cages with perforated floors (Scanbur, Denmark, 53.3x63x38.5 cm) and equipped with an automatic drinking system.
- Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approximately 100 grams per day. In addition hay (BMI, Helmond, The Netherlands) was provided twice a week.
- Water: Free access to tap water.
- The acclimation period was at least 5 days before the start of treatment under laboratory conditions.

A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

All certificates of analysis (diet and water) are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3CºC
- Humidity (%): 30 - 70%
- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial
fluorescent light and 12 hours darkness per day.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped with electric clippers

Vehicle:

water

Remarks:

Milli-U water

Controls:

other: Adjacent areas of the untreated skin of each animal

Amount / concentration applied:

500 mg. The powdery test substance was moistened with Milli-U water, immediately before application, to ensure close contact with the animal's skin.

Duration of treatment / exposure:

4 h of exposure-single application

Observation period:

The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.

Number of animals:

3 males

Details on study design:

TEST SITE/OBSERVATIONS:
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm²). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was applied to the skin of one flank, using a metalline patch# of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Observations for mortality/viability: twice daily. Obervations for toxicity: at least once daily. Body weight: measured prior to application.

SCORING SYSTEM:
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) *
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) was given.

Oedema formation:
0: No oedema
1; Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1 millimeter)
4: Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure)

Irritation parameter:

erythema score

Basis:

animal: #1, #2 and #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: Highest score (1) after 1 h

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: All individual scores: 0

Irritant / corrosive response data:

Very slight erythema in the treated skin-areas of all three rabbits. The skin irritation had resolved within 24 hours after exposure.

Other effects:

No staining of the treated skin by the test substance was observed. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Terracess P is not irritating to skin (4 h exposure to rabbit skin under semi-occlusive conditions).
Terracess P does not have to be classified and has no obligatory labelling requirement for skin irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 November-09 November 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Animals: Albino Rabbit, New Zealand White, (SPF-Quality). Earmark.
- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: Animals used within the study were at least 6 weeks old
- Weight at study initiation: body weights were between 1.0 and 3.5 kg.
- Individually housed in labelled cages with perforated floors (Scanbur, Denmark, dimensions 53.3x63x38.5 cm) and equipped with an automatic drinking system.
- Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day. In addition, hay (BMI, Helmond, the Netherlands) was provided twice a week.
-Free access to tap water.
- Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

All certificates of analysis (diet and water) are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3ºC
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of the test animal remained untreated and served as the reference control.

Amount / concentration applied:

83.7 mg ± 1.2 mg of solid powdery test substance, a volume of approximately 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

3 males.

Details on study design:

Each animal was treated by instillation of approximately 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

OBSERVATIONS:
Mortality/viabiity: twice daily
Toxicity: at least once daily
Body weight: Day of treatment (prior to instillation)

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
0: No ulceration or opacity (may include slight dulling of normal luster)
1: Scattered or diffuse areas of opacity, details of iris clearly visible
2: Easily discernible translucent area, details of iris slightly obscured
3: Nacreous area, no details of iris visible, size of pupil barely discernible
4: Opaque cornea, iris not discernible through the opacity

Area of cornea involved:
0: No ulceration or opacity
1: One quarter or less but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRIS
0: Normal
1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
0: Blood vessels normal
1: Some blood vessels definitely hyperaemic (injected)
2: Diffuse, crimson color, individual vessels not easily discernible
3: Diffuse beefy red

Chemosis (refers to lids and/or nictitating membranes):
0: No swelling
1: Any swelling above normal (includes nictitating membranes)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge:
0: No discharge (may include small amounts observed in inner canthus of normal animals)
1: Any amount different from normal and/or lacrimation
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs (considerable area around the eye)

In case standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: average score over 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Highest score (2) after 1 h and 24 h

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

other: average score over 24, 48 and 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Highest score (2) after 1 h

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Highest score (2) after 1 h

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: Highest score (1) after 1 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Highest score (2) after 1 h

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal: #1, #2, #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

other: average score over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: Highest score (1) after 1 h

Irritant / corrosive response data:

Instillation of approximately 84 mg of the test substance (approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the iris and the conjunctivae. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 72 hours in two animals and within 48 hours in the other animal. Iridial irritation (grade 1) was observed on day 1 and had resolved within 24 hours.

No corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.

There was no evidence of ocular corrosion.

Other effects:

Remnants of the test substance were present in the eyes of all animals on day 1.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Terracess P is not irritating to eye (single instillation of 0.1 mL solid test substance in rabbit eye).
Terracess P does not have to be classified and has no obligatory labelling requirement for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin

In a study performed according to OECD 404 and EC B.4 guidelines, three rabbits were exposed to 0.5 g of Terracess P moistened by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48, and 72 hours after exposure. Very slight erythema in the treated skin areas of all three rabbits were observed but resolved within 24 hours after exposure. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on these observations, Terracess P is considered to be not irritating to the skin.

Eye

In an in vivo study according to OECD 405 and EC B.5 test guidelines, single samples of approximately 0.1 mL of Terracess P were instilled into one eye of each of three rabbits. Instillation of the substance resulted in slight effects on the iris and conjunctivae. Iridial irritation grade 1 was observed at 1 hour after instillation and had resolved within 24 hours in all animals. The irritation of the conjunctivae consisted of redness and chemosis and had completely resolved within 48 hours in one animal and within 72 hours in the other two animals. Treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. Substance remnants were seen in the eyes of all animals on day 1. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on these observations, Terracess P is considered to be not irritating to eyes.

Respiratory

In the acute inhalation toxicity study according to OECD 403, no signs of irritation were observed in the exposed animals. Terracess P is expected to cause no respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:
One key study available.

Justification for selection of eye irritation endpoint:
One key study available.

Justification for classification or non-classification

Based on the available studies, Terracess P does not have to be classified for skin and eye irritation according to Directive 67/548/EEC and CLP Regulation EC (No.) 1272/2008