[No public or meaningful name is available]

Endpoint summary

Description of key information

In an OECD 404 study the substance is considered to be non-irritating to the rabbit skin.

 

In an OECD 405 study the test substance is considered to be “not irritating” 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

Study period:

26 September 2006 to 23 November 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test system
Number of animals per test: 3 (Animals of both sexes were used)
Age at treatment: 13-14 weeks (male); 13-14 weeks (females)
Body Weight at treatment: 2869 g (male); 2485 - 2488 g (females)
Identification: By unique cage number and corresponding ear number.

Acclimatization: Under laboratory conditions after health examination. Only
animals without any visual signs of illness were used for the study.

Environmental conditions
Air-conditioned with ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.

Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum.

Water Community tap water from Füllinsdorf, ad libitum.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL of the test substance was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 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.

Duration of treatment / exposure:

The duration of treatment was 4 hours. Then the dressing was removed and the skin was
flushed with lukewarm tap water to clean the application site so that any reactions (erythema)
were clearly visible at that time.

Observation period:

Viability/Mortality: Daily from acclimatization of the animals to the termination of test.

Clinical signs: Daily from acclimatization of the animals to the termination of test.

Body weights: At start of acclimatization, on the day of application and at termination of observation.

Skin reaction: The skin reaction was assessed at approximately 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after exposure (removal of the dressing, gauze patch and test item).

Number of animals:

As it was suspected that the test item might produce irritancy, a single animal (one female)
was treated first. As neither a corrosive effect nor a severe irritant effect was observed after
the 4-hour exposure, the test was completed using the two remaining animals for an
exposure period of four hours.

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 10 days.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch
removal) for each animal for erythema/eschar grades and for oedema grades, separately.
The mean erythema/eschar score of the three animals was 1.33, 1.00 and 1.00, respectively
and the mean oedema score was 0.33 for each of the three animals.

Very slight to well-defined erythema was present in all the animals at the 1-hour reading and
persisted in two animals until the 72-hour and in one until the 7-day reading. Very slight
oedema was noted in two animals at the 1-hour reading and in three animals at the 24-hour
reading. In addition scaling was present in one animal from 72 hours to 10 days after
treatment.

No abnormal findings were observed on the treated skin of any animal 14 days after
treatment, the end of the observation time.

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.

Neither alterations of the treated skin were observed nor were corrosive effects evident on
the skin.

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

Interpretation of results:

GHS criteria not met

Conclusions:

In an OECD 404 study the substance is considered to be non-irritating.

Executive summary:

The primary skin irritation potential of the test substance was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 mL 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, as well as 7, 10 and 14 days after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. 

The mean erythema/eschar score of the three animals was 1.33, 1.00 and 1.00, respectively and the mean oedema score was 0.33 for each of the three animals.
The application of the test substance to the skin resulted in moderate signs of irritation. These included erythema, oedema and scaling. These effects were reversible and were no longer evident 14 days after treatment, the end of the observation period for all animals. 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.
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), and is considered to be “not irritating” to rabbit 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

Study period:

27 September 2006 to 1 December 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test animals
Number of animals per test: 3 (Animals of both sexes were used)
Age at treatment: 16-17 weeks (male); 12-15 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

Environmental conditions
Air-conditioned with ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.

Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance
diet ad libitum.

Water Community tap water from Füllinsdorf, ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL (per animal) of the test substance was measured with a syringe and applied undiluted as it
was delivered by the Sponsor.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48, 72 hours , as well as 7
days after administration.

Number of animals or in vitro replicates:

As it was suspected that the test item might produce irritancy, a single animal (one female)
was treated first. As neither a corrosive effect nor a severe irritant effect was observed after
the 1- and 24-hour examinations, the test was completed using the two remaining animals.

Details on study design:

On the day of treatment, 0.1 mL of of the test substance was placed in the conjunctival sac of the left 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 to prevent loss of test item. The right eye
remained untreated and served as the reference control. The treated eyes were not rinsed
after instillation.

No necropsy was performed on the animals sacrificed at termination of observation.
The animals were killed by intravenous injection of pentobarbitone into the ear vein at a dose
of at least 1 mL/kg body weight and discarded.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Other effects:

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

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

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. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.00, 0.33 and 0.33 for reddening and 0.00 for chemosis for all the animals.

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 all animals at the 1-hour reading and persisted in two animals until 24 hours after application.

Slight swelling (chemosis) of the conjunctivae was observed in all animals at the 1-hour reading.

Slight reddening of the sclerae was present at 1 hour after treatment in all animals.

One animal showed a slight ocular discharge at the 1-hour reading.

No abnormal findings were observed in the treated eye of any animal 48 hours after treatment.

 

No corrosion of the cornea was observed at any of the reading times.

Interpretation of results:

GHS criteria not met

Conclusions:

In an OECD 405 study the test substance is considered to be “not irritating” to the rabbit eye.

Executive summary:

The primary eye irritation potential of the test substance was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 mL 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, as well as 7 days 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. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.00, 0.33 and 0.33 for reddening and 0.00 for chemosis for all the animals.

 

The instillation of the test substance into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, chemosis and discharge. 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. 

 

Based upon the referred classification criteria (Commission Directive 2001/59/EC of 
August 06, 2001), the test substance is considered to be “not irritating” to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available