Rabitle FP-100

Endpoint summary

Description of key information

Based upon the CLP criteria FP-100 is considered to be “not irritating” to rabbit skin.
Based upon the  CLP criteria, FP-100 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:

Experimental start date: 14th March 2007 Experimental completion date: 22nd March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - Study generated according to generally valid and/or internationally accepted testing guidelines - Performed according to GLP - Test parameters based on specific testing guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

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

Deviations:

yes

Remarks:

Study Plan Amendment No. 1: The animals were not sacrificed. On completion of the observation period they were reallocated to the eye irritation study (RCC Study B18088). Study Plan Amendment No. 2: Change of study director and deputy.

Principles of method if other than guideline:

ANIMAL WELFARE: This study was performed in an AAALAC-approved laboratory in accordance with the Swiss Animal Protection Law under license no. 55.

CLASSIFICATION GUIDELINES: Commission Directive 2001/59/EC adapting to technical progress for the 28th time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances,
August 06, 2001 (Official Journal of the European Communities Nr. L 225/1, August 21, 2001).

GLP compliance:

yes (incl. QA statement)

Species:

other: Rabbit (New Zealand White) young adult

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/The Netherlands, Postbus 6174, NL-5960 AD Horst/The Netherlands
- Age at study initiation: Age at treatment: 12 weeks (male), 12 weeks (females)
- Weight at study initiation:
Animal No. Sex First Day of Acclimatization Day of Treatment
91 male 2190g 2348g
92 female 1831g 2162g
93 female 2146g 2209g

- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Fullinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83/05 and 09/07) provided by Provimi Kliba AG, CH-4303 Kaiseraugst, Results of analysis for contaminants are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 14th March 2007 – 18th March 2007. Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
Standard Laboratory Conditions
- Temperature (°C): Air-conditioned with ranges for room temperature 17-23°C
- Humidity (%):relative humidity 30-70%
(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 and, therefore, these data are not reported but are retained at RCC).
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Purified Water.

Controls:

no

Amount / concentration applied:

500 mgTEST MATERIAL
- Amount(s) applied (volume or weight with unit): On the day of treatment, 0.5 g of FP-100 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:

4 h

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Left flank
- % coverage: approximately 100 cm2 (10cm x 10 cm)
- Type of wrap if used: Semi-occlusive dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 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.
- Time after start of exposure: The duration of treatment was 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

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Irritant / corrosive response data:

IRRITATION: 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 erythema/eschar and oedema for each of the three animals was therefore 0.

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

Other effects:

No abnormalities were observed during the testing/observation period.VIABILITY/MORTALITY/CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

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

BODY WEIGHTS
The body weights of all rabbits were considered to be within the normal range of variability.
Animal No. Sex Last day of observation
91 male 2536g
92 female 2273g
93 female 2404g

Interpretation of results:

other: not classified

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FP-100 is considered to be “not irritating” to rabbit skin.

Executive summary:

The primary skin irritation potential of FP-100 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 erythema/eschar 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. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FP-100 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:

Experimental start date: 22nd March 2007 Experimental completion date: 30th March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - Study generated according to generally valid and/or internationally accepted testing guidelines - Performed according to GLP - Test parameters based on specific testing guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Study Plan Amendment No. 1: Change of study director and deputy

Principles of method if other than guideline:

CLASSIFICATION GUIDELINES: Commission Directive 2001/59/EC adapting to technical progress for the 28 time Council
Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances,
August 06, 2001 (Official Journal of the European Communities Nr. L 225/1, August 21, 2001).

ANIMAL WELFARE: This study was performed in an AAALAC-approved laboratory in accordance with the Swiss Animal Protection Law under license no. 54.

GLP compliance:

yes (incl. QA statement)

Species:

other: Rabbit (New Zealand White) young adult SPF

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: Age at treatment: 13 weeks (male), 13 weeks (females)
- Weight at study initiation:

Animal No. Sex First Day of Acclimatization Day of Treatment
91 male 2533g 2624g
92 female 2289g 2460g
93 female 2400g 2697g


- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 01/07) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 22nd March 2007 – 26th March 2007. Acclimatization Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
Conditions Standard Laboratory Conditions
- Temperature (°C): Air-conditioned with ranges for room temperature 17-23 °C
- Humidity (%): Relative humidity 30-70% (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 and, therefore, these data are not reported but are retained at RCC).
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 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.

Vehicle:

unchanged (no vehicle)

Controls:

other: Right eye remained untreated and served as the reference control

Amount / concentration applied:

100 MG
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g (per animal) of FP-100 was weighed and applied undiluted as it was delivered by the sponsor

Duration of treatment / exposure:

treated eyes were not rinsed after instillation

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

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: The eyes of each animal were examined approximately 1, 24, 48, 72 hours after administration. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0.33

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

ca. 0

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

ca. 0

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 2 days
Not Irritating - IRRITATION: 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, 0.00 and 0.33 for reddening and 0.00 for chemosis for each of the three animals.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

A slight reddening of the conjunctivae was noted in the three animals 1 hour after installation which persisted in one female up to the 24-hour reading. Additionally, all animals expressed a slight reddening of the sclerae at the 1-hour observation, only. White test item remnants were present in all treated animals one hour after installation.

Other effects:

The installation of FP-100 into the eye resulted in mild,
early-onset and transient ocular changes, such as reddening
of the conjuctivae and sclerae. These effects were
reversible and were no longer evident 48 hours to 72 hours
after treatment.

VIABILITY/MORTALITY AND CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

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

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

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

Animal No. Sex Last Day of Observation
91 male 2721g
92 female 2573g
93 female 2830g

No statistical analysis was performed   NECROPSY: No necropsy was performed on the animals sacrificed at termination of observation. The surviving 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.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

Based upon the referred classification (Commission Directive 2001/591EC of August 06, 2001), FP-100 is considered to be “not irritating” to the rabbit eye.

Executive summary:

The primary eye irritation potential of FP-100 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. 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, 0.00 and 0.33 for reddening and 0.00 for chemosis for each of the three animals.   The instillation of FP-100 into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae. These effects were reversible and were no longer evident 48 to 72 hours after treatment, the end of the observation period for all animals. 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.   Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), FP-100 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

Additional information

The primary skin irritation potential of FP-100 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 erythema/eschar 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. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), FP-100 is considered to be “not irritating” to rabbit skin.

The primary eye irritation potential of FP-100 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. 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, 0.00 and 0.33 for reddening and 0.00 for chemosis for each of the three animals.   The instillation of FP-100 into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae. These effects were reversible and were no longer evident 48 to 72 hours after treatment, the end of the observation period for all animals. 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.   Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), FP-100 is considered to be “not irritating” to the rabbit eye.

Justification for classification or non-classification

FP-100 was determined to be not irritating to skin or eye