Registration Dossier

Administrative data

Description of key information

Based on a weight of evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study, OFPMA is not irritating to skin.

 

Based on the results of a study equivalent to OECD Guideline 405 (Acute Eye Irritation / Corrosion), OFPMA has probability for weak eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Remarks:
Dermal Prenatal Developmental Toxicity Study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
3 October 2007 to 18 January 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
This endpoint study record is part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
other:
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to same study
Guideline:
other: equivalent to: OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
Only dermal irritation observations reported
Principles of method if other than guideline:
An OECD Guideline 414 (Prenatal Developmental Toxicity Study) dermal exposure equivalent study was completed. The skin irritation observations are reported.
GLP compliance:
no
Remarks:
The study was not commissioned with compliance with REACH as a goal, rather the study was commissioned during early product development.
Specific details on test material used for the study:
Purity: 99%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: The animals were approximately 5.5 months old upon receipt.
- Weight at study initiation: Body weight values ranged from 2947 g to 4279 g on gestation day 0.
- Fasting period before study: Not reported
- Housing: housed individually
- Diet: The basal diet was offered in 25 g increments 3 times per day on the day of arrival and in increased amounts over the next few days, until the animals gradually achieved ad libitum status prior to the dose administration period; basal diet was offered ad libitum thereafter.
- Water: ad libitum
- Acclimation period: Prior to the initiation of dose administration, the animals were acclimated to wearing Elizabethan restraint collars. The collars were affixed to each rabbit on gestation days 3, 4, 5 and 6 for approximately 1, 2, 4 and 6 hours, respectively.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19±3°C
- Humidity (%): 50±20%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 4 November 2007 (first gestation day 0) To: 27 November 2007 (Last laparohysterectomy)
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
The dosage level was 1300 mg/kg/day administered at a dosage volume of 0.91 mL/kg.
Duration of treatment / exposure:
6 hours of exposure per day for 14 days (gestation days 7-20)
Observation period:
The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings.
Number of animals:
22 females per dose
Details on study design:
TEST SITE
- Area of exposure: The hair was clipped from the back of each animal, from the scapula (shoulder) to the wing of the ileum (hipbone) and halfway down the flank of each side of the animal. Doses were evenly applied using a rubber policeman covered glass rod over the clipped, unabraded area. The corners of the application site were marked with indelible ink to allow proper identification of the treated and untreated skin. Elizabethan collars were applied to restrict access to the wrapped dosing site.
- % coverage: approximately 7.9%
- Type of wrap if used: The application site for each animal was covered with 8-ply gauze, covered with an occluded non-porous latex bandage and held in place with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual material on the skin was visually estimated and recorded, and the test sites were gently washed twice (the second wash immediately following the first) with a 70:30 isopropanol:water solution and disposable paper towels to remove any residual vehicle or test article.
- Time after start of exposure: After 6-hour exposure period

OBSERVATION TIME POINTS
The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings
4-STEP GRADING SYSTEM (Draize, 1965)
Erythema and Eschar Formation:
- 0: No erythema
- 1: Very slight erythema (barely perceptible, edges of area not well defined)
- 2: Sight erythema (pale read in colour and edges definable)
- 3: Moderate to severe erythema (definite red in colour and area well defined)
- 4: Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth)
Edema Formation:
- 0: No edema
- 1: Very slight edema (barely perceptible, edges of area not well defined)
- 2: Slight edema (edges of area well defined by definite raising)
- 3: Moderate edema (raised approximately 1 mm)
- 4: Severe edema (raised more than 1 mm and extending beyond area of exposure)

Further study design regarding prenatal development toxicity are discussed elsewhere in this dossier.
Irritation parameter:
overall irritation score
Remarks:
on day 1 following 6-hour exposure
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
probability of weak irritation
Remarks:
following repeated exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritant / corrosive response data:
No dermal irritation effects were observed following single exposure. Very slight erythema was noted in 4 females from 1 to 3 consecutive days during gestiation days 12-14. Due to the absence of this finding in the vehicle control group, these occurrences of very slight erythema were considered to be test article-related; however, because of the transient nature, limited incidence and minimal severity of this finding, it was not considered to be adverse.
In addition, desquamation was noted in 2 and 7 females in the vehicle control and 1300 mg/kg/day group, respectively, prior to dose application; this finding was observed generally beginning as early as gestation day 11 and continuing through gestation day 16. This finding persisted to the time of unwrap (following 6 hours of exposure) in 3 test article-treated females (nos. 52135, 52137 and 52142) during gestation days 14-16.
Interpretation of results:
study cannot be used for classification
Remarks:
Weight of Evidence classification: GHS criteria not met
Conclusions:
Evidence of minimal dermal irritation (very slight erythema) was noted in 4 females from 1 to 3 consecutive days during gestation days 12-14. In addition, desquamation was noted in 2 and 7 females in the vehicle control and 1300 mg/kg/day group, respectively, prior to dose application; this finding was observed generally beginning as early as gestation day 11 and continuing through gestation day 16. This finding persisted to the time of unwrap (following 6 hours of exposure) in 3 test article-treated females (nos. 52135, 52137 and 52142) during gestation days 14-16.
Executive summary:

As part of a weight of evidence approach, the skin irritation observation reported during a rabbit dermal exposure study equivalent to OECD Guideline 414 (Prenatal Developmental Toxicity Study) were considered. The test article was administered by dermal exposure to clipped dorsum (approximately 8% of total body surface area) to 2 groups of 22 time-mated female New Zealand White rabbits once daily, from gestation days 7-20. The application site for each animal was covered with 8-ply gauze, covered with an occluded non-porous latex bandage and held in place with non-irritating tape. Elizabethan collars were applied to restrict access to the wrapped dosing site. The dosage level was 1300 mg/kg/day administered at a dosage volume of 0.91 mL/kg. A concurrent control group of 22 time-mated females received the vehicle (deionized water) on a comparable regimen at a dose volume of 1.3 mL/kg. The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings. The prenatal developmental toxicity study continued to determine potential toxicity as described elsewhere within this dossier.

 

Minimal dermal irritation (very slight erythema) was noted in 4 females from 1 to 3 consecutive days during gestation days 12-14.

In addition, desquamation was noted in 2 and 7 females in the vehicle control and 1300 mg/kg/day group, respectively, prior to dose application; this finding was observed generally beginning as early as gestation day 11 and continuing through gestation day 16. This finding persisted to the time of unwrap (following 6 hours of exposure) in 3 test article-treated females (nos. 52135, 52137 and 52142) during gestation days 14-16.

Endpoint:
skin irritation: in vivo
Remarks:
Dermal Prenatal Developmental Toxicity Study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
4 November 2007 to 18 January 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
This endpoint study record is part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to same study
Guideline:
other: equivalent to: OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
Only dermal irritation observations reported
Principles of method if other than guideline:
An OECD Guideline 414 (Prenatal Developmental Toxicity Study) dermal exposure equivalent study was completed. The skin irritation observations are reported.
GLP compliance:
no
Remarks:
The study was not commissioned with compliance with REACH as a goal, rather the study was commissioned during early product development.
Specific details on test material used for the study:
Purity: 99%
Species:
rat
Strain:
other: Crl:CD(SD)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Portage, Michigan
- Age at study initiation: Approximately 84 to 91 days old upon receipt
- Weight at study initiation: a minimum of 220 g at gestation day 5 (205-308 g on Gestation Day 5)
- Fasting period before study: No
- Housing: Upon arrival and until pairing, all rats were individually housed
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Prior to the initiation of dose administration, the animals were acclimated to wearing Elizabethan restraint collars. The collars were affixed to each rat on gestation days 4 and 5 for approximately 1 and 3 hours, respectively.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 50±20%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 4 November 2007 (first gestation day 0) To: 27 November 2007 (Last laparohysterectomy)
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
The dosage level was 1300 mg/kg/day administered at a dosage volume of 0.91 mL/kg.
Duration of treatment / exposure:
6-hour exposure period per day for 12 days (gestation days 6-17).
Observation period:
The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings.
Number of animals:
25 females per dose
Details on study design:
TEST SITE
- Area of exposure: Back of animals, from the scapula to the wing of the ileum (hipbone) and halfway down the flank of each side of the animal. Doses were evenly applied using a rubber policeman covered glass rod over the clipped, unabraded area. The corners of the application site were marked with indelible ink to allow proper identification of the treated and untreated skin. Elizabethan collars were applied to restrict access to the wrapped dosing site.
- % coverage: The mean areas of coverage were approximately 7.85%.
- Type of wrap if used: The application site for each animal was covered with 8-ply gauze, covered with an occluded non-porous latex bandage and held in place with non-irritating tape.


REMOVAL OF TEST SUBSTANCE
- Washing: Residual material on the skin was visually estimated and recorded, and the test sites were gently washed with a 70:30 isopropanol:water solution and disposable paper towels to remove any residual vehicle or test article.
- Time after start of exposure: After 6-hour exposure period

OBSERVATION TIME POINTS
The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings

4-STEP GRADING SYSTEM (Draize, 1965)
Erythema and Eschar Formation:
- 0: No erythema
- 1: Very slight erythema (barely perceptible, edges of area not well defined)
- 2: Sight erythema (pale read in colour and edges definable)
- 3: Moderate to severe erythema (definite red in colour and area well defined)
- 4: Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth)
Edema Formation:
- 0: No edema
- 1: Very slight edema (barely perceptible, edges of area not well defined)
- 2: Slight edema (edges of area well defined by definite raising)
- 3: Moderate edema (raised approximately 1 mm)
- 4: Severe edema (raised more than 1 mm and extending beyond area of exposure)


Further study design regarding prenatal development toxicity are discussed elsewhere in this dossier.
Irritation parameter:
overall irritation score
Remarks:
on Day 1 following 6-hour exposure
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
no dermal irritation reported at any time point for any animal
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritant / corrosive response data:
No dermal irritation effects were observed.
Interpretation of results:
study cannot be used for classification
Remarks:
Weight of Evidence classification: GHS criteria not met
Conclusions:
No skin irritation was reported during the daily observations during a rat dermal exposure study equivalent to OECD Guideline 414 (Prenatal Developmental Toxicity Study).
Executive summary:

As part of a weight of evidence approach, the skin irritation observation reported during a rat dermal exposure study equivalent to OECD Guideline 414 (Prenatal Developmental Toxicity Study) were considered. The test article was administered by dermal exposure to clipped dorsum (approximately 8% of total body surface area) to 2 groups of 25 time-mated female Crl:CD(SD) rats once daily from gestation days 6 through 17. The application site for each animal was covered with 8-ply gauze, covered with an occluded non-porous latex bandage and held in place with non-irritating tape. Elizabethan collars were applied to restrict access to the wrapped dosing site. The dosage level was 1300 mg/kg/day administered at a dosage volume of 0.9 mL/kg. A concurrent control group of 25 time-mated females received the vehicle (deionized water) on a comparable regimen at a dosage volume of 1.3 mL/kg. The application site was scored daily (prior to dose administration and following removal of the dressing) for erythema, edema and other dermal findings. The prenatal developmental toxicity study continued to determine potential toxicity as described elsewhere within this dossier.

 

No skin irritation was reported during the daily observations.

Endpoint:
skin irritation: in vitro / ex vivo
Remarks:
In Vitro Percutaneous Absorption
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08 April 2010 to 05 May 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
This endpoint study record is part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to same study
Guideline:
other: OECD Guideline 428 (Skin Absorption: In Vitro Method)
Version / remarks:
Dermal irritation observations reported
Principles of method if other than guideline:
An OECD Guideline 428 (Skin Absorption: In Vitro Method) study was conducted. The dermal irritation observations are reported.
GLP compliance:
yes
Specific details on test material used for the study:
Specific details on test material used for the study
- Radiolabelling: yes
- Source and lot/batch No.of test material: American Radiolabelled Chemicals Inc, batch no. 090109
- Radiochemical purity: 93.6%
- Specific activity: 5 mCi/mmol
- Locations of the label: carbonyl carbon
Test system:
human skin model
Details on animal used as source of test system:
Six samples of full-thickness human skin (4 abdomen and 2 breast) were obtained from female patients aged 19 to 63 years old attending St. John’s Hospital, NHS Lothian, Livingston, UK. On arrival at Charles River, these samples were cleaned of subcutaneous fat and connective tissue using a scalpel blade. The skin samples were washed in cold running water and dried using tissue paper.

The skin samples were then cut into smaller pieces (where appropriate), wrapped in aluminium foil, put into self sealing plastic bags and stored at -20°C until they were used in the study.
Vehicle:
other: leave-on hair styling cream
Amount/concentration applied:
The leave-on hair styling cream containing 2% (w/v) radiolabelled test substance (concentration by radioactivity 2.11% w/v) was applied, at an application rate of about 20 mg/cm² (469 μg equiv. OFPMA/cm²)
Duration of treatment / exposure:
24 hours (single exposure)
Number of replicates:
24 human split thickness skin membranes (12 occluded and 12 unoccluded)
Type of coverage:
other: occluded and unoccluded skin were assessed
Vehicle:
other: leave-on hair styling cream
Details on study design:
SKIN PREPARATION
- Source of skin: female patients aged 19 to 63 years old attending St. John’s Hospital, NHS Lothian, Livingston, UK
- Type of skin: breast or abdomen
- Preparative technique: Split-thickness membranes were prepared by pinning the full-thickness skin, stratum corneum uppermost, onto a raised cork board and cutting at a setting equivalent to 200-400 μm depth using a Zimmer® electric dermatome.
- Thickness of skin (in mm): full-thickness 1430 to 2130 μm; split-thickness 400 μm
- Membrane integrity check: A tritiated water barrier integrity test was performed and any human skin sample exhibiting absorption greater than 0.6% of the applied dose was excluded from subsequent absorption measurements.
- Storage conditions: The split-thickness membranes were stored at about -20°C.

PRINCIPLES OF ASSAY
- Diffusion cell: automated flow-through diffusion cell apparatus
- Receptor fluid: Phosphate buffered saline containing polyoxyethylene 20-oleyl ether (PEG, about 6%, w/v), sodium azide (about 0.01%), streptomycin (about 0.1 mg/mL) and penicillin G (about 100 units/mL)
- Solubility od test substance in receptor fluid: solubility of OFPMA in phosphate buffered saline is 900 mg/L
- Flow-through system: flow rate 1.451 to 1.571 mL/h
- Test temperature: 31.9 to 32.8 °C
- Occlusion: For twelve of the cells (Test Group 1), the donor chambers were occluded with an occlusive trap containing carbon filters. For the other twelve cells (Test Group 2), the donor chamber was left open to the atmosphere and the system was used inside a fume hood.
Remarks on result:
not measured/tested
Other effects / acceptance of results:
Following topical application of [14C]-OFPMA in the test preparation (2%, w/v) to occluded skin, the absorbed dose and dermal delivery of [14C]-OFPMA were 1.18% (5.52 μg equiv./cm2) and 1.53% (7.18 μg equiv./cm2), respectively. There was no report of damage to the stratum corneum.
Interpretation of results:
study cannot be used for classification
Remarks:
Weight of Evidence classification: GHS criteria not met
Conclusions:
Following topical application of [14C]-OFPMA in the test preparation (2%, w/v) to occluded skin, the absorbed dose and dermal delivery of [14C]-OFPMA were 1.18% (5.52 μg equiv./cm2) and 1.53% (7.18 μg equiv./cm2), respectively.  There was no report of damage to the stratum corneum.
Executive summary:

The stratum corneum was observed during a skin irritation observation during a OECD Guideline 428 (Skin Absorption: In Vitro Method) and considered as part of the overall weight of evidence for skin irritation. The in vitro dermal absorption of OFPMA was determined according to OECD Guideline 428 and the accompanying OECD Guidance Document No. 28. Split-thickness human skin membranes were mounted into flow-through diffusion cells. The test preparation containing [14C]-OFPMA (2%, w/v) was applied, at an application rate of about 20 mg/cm² (469 μg equiv. OFPMA/cm²), to 24 human split-thickness skin membranes mounted into flow through diffusion cells in vitro. Immediately after dosing, the donor chamber of 12 cells was covered with an occlusive trap containing carbon filters in an attempt to collect any volatile OFPMA. The remaining 12 cells remained unoccluded and so were open to the atmosphere, simulating the intended consumer use. The integrity of the stratum corneum was observed prior to assessment of the absorbed dose. The Percutaneous absorption study continued to determine dermal adsorption as described elsewhere within this dossier.

 

There was no report of damage to the stratum corneum.

Endpoint:
skin irritation: in vivo
Remarks:
skin irritation reported in LLNA study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
10 May 2007 to 11 January 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
This endpoint study record is part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Reason / purpose:
reference to same study
Guideline:
other: equivalent to: OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
Skin irritation observations reported
Principles of method if other than guideline:
A study equivalent to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay) with no deviations was conducted. Application sight was observed for signs of irritation.
GLP compliance:
no
Remarks:
The study was not commissioned with compliance with REACH as a goal, rather the study was commissioned during early product development.
Specific details on test material used for the study:
Purity: 98%
Species:
mouse
Strain:
CBA
Remarks:
CBA:J
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The Jackson Laboratory, Bar Harbor, ME.
- Females nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: Animals were examined to ensure good health and suitability as test subjects for use in the study.
- Age at study initiation: appromixately 7-8 weeks
- Weight at study initiation: 17-21g
- Housing: housed individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week
- Indication of any skin lesions: Animals were examined to ensure good health and suitability as test subjects for use in the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 37-61%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 / 12

- IN-LIFE DATES: From: 07 June 2007 To: 11 June 2007
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
other: acetone/olive oil (4:1 v/v)
Amount / concentration applied:
11.3, 22.5, 33.8 and 45% in an acetone:olive oil (4:1) vehicle.
Highest concentration tested was 45% which was considered as the solubility limit in an acetone:olive oil 4:1 mixture.
Number of animals:
5 females/dose
Details on study design:
Five mice per group were dosed with the test substance at concentrations of 11.3, 22.5, 33.8 and 45% in an acetone:olive oil (4:1) vehicle. The mice were dosed once daily at approximately the same time for three consecutive days. All mice were observed twice daily on dosing days immediately prior to and approximately 4-6 hours after dosing, then once daily for moribundity, mortality, and any signs of toxicity and skin reactions.

Further study design relating to the investigation for skin sensitization is reported elsewhere within this dossier.
Irritation parameter:
other: irritation observation
Basis:
animal: all animals
Time point:
24 h
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Irritant / corrosive response data:
There were no mortalities and no signs of systemic toxicity or irritation noted for the test and control animals.
Interpretation of results:
study cannot be used for classification
Remarks:
Weight of Evidence classification: GHS criteria not met
Conclusions:
No skin irritation was reported during the daily observations during a study equivalent to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay).
Executive summary:

As part of a weight of evidence approach, the skin irritation observation reported during a study equivalent to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay) with no deviations were considered. Five mice per group were dosed with the test substance at concentrations of 11.3, 22.5, 33.8 and 45% in an acetone:olive oil (4:1) vehicle following 1 week of acclimation period. The mice were dosed once daily at approximately the same time for three consecutive days. All mice were observed twice daily on dosing days immediately prior to and approximately 4-6 hours after dosing, then once daily for moribundity, mortality, and any signs of toxicity and skin reactions. The skin sensitization study continued to determine skin sensitization potential as described elsewhere within this dossier.

There were no mortalities and no signs of systemic toxicity or irritation noted for the test and control animals.

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:
14 May 2007 to 31 October 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
The study was not commissioned with compliance with REACH as a goal, rather the study was commissioned during early product development.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 08230AB
- Purity: 99.8%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabbit Ranch (Gary, IN)
- Age at study initiation: 4 months of age
- Weight at study initiation: 2.84-3.09 kg
- Housing: housed individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 - 21.2°C
- Humidity (%): 27-401%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 16 May 2007 To: 24 May 2007
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL of undiluted test substance
Duration of treatment / exposure:
single exposure; the treated eye of each rabbit was rinsed with water 24 hours after dosing.
Observation period (in vivo):
1, 24, 48, 72-hours after test substance administration
Duration of post- treatment incubation (in vitro):
Not applicable
Number of animals or in vitro replicates:
3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye of each rabbit was rinsed with water
- Time after start of exposure: 24 hours after dosing.

SCORING SYSTEM: according to EEC grading guidelines

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
overall irritation score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Remarks on result:
probability of weak irritation
Remarks:
conjunctiva discharge score of 1 at 1 hour in 1 animal
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Slight, clear fluid was discharged on the fur below the eye of two animals at the 1-hour time point. The animals were recovered from the signs of discharge at the 24-hour time point.
Other effects:
Throughout the study, no deaths occurred and none of the animals were found moribund.
Interpretation of results:
GHS criteria not met
Conclusions:
The mean eye irritation score at 24, 48, and 72 hours for corneal opacity, iris lesion, conjunctival redness and chemosis were all 0 for 3 animals.
Executive summary:

Undiluted test substance was placed in the conjunctival sac of the right eye of each of the three female rabbits used in the study. The untreated left eye of each rabbit served as a control for comparison purposes. The treated eye of each rabbit was rinsed with water 24 hours after administration of the test substance and scored for irritation at 1, 24, 48, and 72 hours post-dose. 

 

Slight, clear fluid was discharged on the fur below the eyes of two animals at the 1-hour scoring interval. The rabbits completely recovered from signs of ocular discharge at the 24-hour scoring interval. 

The mean scores for corneal opacity, iris lesion, conjunctival redness and chemosis were all 0. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Skin irritation has been assessed as part of a Weight of Evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation reported during an LLNA study and the results of an in vitro dermal adsorption study. The data sources are in agreement regarding dermal irritation and are sufficient to fulfil the information requirements.

Under the conditions employed in both human RIPT studies study, there was no evidence of sensitization to two hair spray formulations or two hair cream formulations containing 2% OFPMA. Examination of the data also indicate an absence of irritation reactions. Dermal irritation observations were reported during the investigation of potential prenatal developmental toxicity in rats and rabbits. No skin irritation was reported in rats and only very slight irritation was noted in 4 female rabbits from 1 to 3 consecutive days during gestation days 12-14 following daily 6-hour exposure to OFPMA. No skin irritation was reported during the daily observations during a study equivalent to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay). Finally, there was no report of damage to the stratum corneum during an OECD Guideline 428 (Skin Absorption: In Vitro Method).

Overall, the reported dermal irritation reactions are in agreement and are sufficient to conclude that OFPMA does not fulfil the criteria for skin corrosion/irritation classification according to European CLP Regulation (EC) No 1272/2008 (as amended).

Eye Irritation:

Undiluted test substance was placed in the conjunctival sac of the right eye of each of the three female rabbits used in the study. The untreated left eye of each rabbit served as a control for comparison purposes. The treated eye of each rabbit was rinsed with water 24 hours after administration of the test substance and scored for irritation at 1, 24, 48, and 72 hours post-dose. 

 

Slight, clear fluid was discharged on the fur below the eyes of two animals at the 1-hour scoring interval. The rabbits completely recovered from signs of ocular discharge at the 24-hour scoring interval. 

 

The mean scores for corneal opacity, iris lesion, conjunctival redness and chemosis were all 0.  OFPMA does not fulfil the criteria for serious eye damage/eye irritation classification according to European CLP Regulation (EC) No 1272/2008 (as amended).

Justification for classification or non-classification

Based on a weight of evidence approach comprising a direct observation from RIPT studies, dermal irritation reported during developmental toxicity studies, irritation report during and LLNA study and the results of an in vitro dermal adsorption study, the test substance is not considered to be irritant to skin. Therefore, the substance does not fulfil the criteria for skin corrosion/irritation classification according to European CLP Regulation (EC) No 1272/2008 (as amended).

The mean scores for corneal opacity, iris lesion, conjunctival redness and chemosis were all 0 according to a study equivalent to OECD Guideline 405 (Acute Eye Irritation / Corrosion).  OFPMA does not fulfil the criteria for serious eye damage/eye irritation classification according to European CLP Regulation (EC) No 1272/2008 (as amended).