Producto P0310

Endpoint summary

Description of key information

Skin irritation: Key study: OECD guideline 404 and EU method B.4. GLP study.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythemaleschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Eye irritation: Key study: OECD guideline 405 and EU method B.5. GLP study.

The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae and chemosis. These effects were reversible and were no longer evident 48 hours after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst 1, The Netherlands; Postbus 6174, NL-5960 AD Horst 1, The Netherlands
- Age at study initiation: 14 weeks (males); 13, 14 weeks (females)
- Weights at study initiation: Male: 2707 g; Females: 2443 and 2356 g
- Housing: lndividually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 (batch no. 65/06, Provirni Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83106) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.

Type of coverage:

semiocclusive

Preparation of test site:

other: Applied to the intact left flank of each of three young adult rabbits.

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,5 g per animal and then moistened with approximately 0,5 mL of purified water before application.

Duration of treatment / exposure:

4 hours

Observation period:

The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

Number of animals:

3 animals, both sexes.

Details on study design:

TEST SITE
- Area of exposure: Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm).
- Type of wrap if used: On the day of treatment, 0.5 g of the test substance was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythemaleschar and oedema for each of the three animals was therefore 0. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

No staining produced by the test item of the treated skin was observed.

The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythemaleschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythemaleschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV Kreuzelweg 53 NL-5961 NM Horst / The Netherlands Postbus 6174 NL-5960 AD Horst / The Netherlands
- Age at study initiation: 13 weeks (male), 12-13 weeks (females)
- Weight at study initiation: 2948 g (male), 2676 and 2636 g (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 (batch no. 65/06, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 g (per animal) of the test item was weighed and applied undiluted

Duration of treatment / exposure:

The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits.

Observation period (in vivo):

Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation.

Number of animals or in vitro replicates:

1 male, 2 females.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: The eye reactions were assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004. Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Irritant / corrosive response data:

All individual mean scores for each of the three animals were 0.00 in this study.
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.
Slight reddening of the conjunctivae was noted in the three test animals one hour after the test item instillation. In addition, sclerae of two animals were found slightly red and the conjunctiva of one animal slightly swollen at this reading. Twenty-four hours after the treatment slight reddening of the sclera was still noted in one animal and thereafter no abnormal findings were noted.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae and chemosis. These effects were reversible and were no longer evident 48 hours after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. All individual mean scores for each of the three animals were 0.00 in this study. The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae and chemosis. These effects were reversible and were no longer evident 48 hours after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: Key study: OECD guideline 404 and EU method B.4. GLP study.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythemaleschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

Eye irritation: Key study: OECD guideline 405 and EU method B.5. GLP study.

The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae and chemosis. These effects were reversible and were no longer evident 48 hours after treatment. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Justification for classification or non-classification

Based on the available information, the substance is not classified as skin irritant or eye irritant according to CLP Regulation (EC) 1272/2008.