Registration Dossier

Administrative data

Description of key information

Not irritating to skin or eye

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Remarks:
skin irritation/corrosion in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 December 1999-4 January 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Likely performed under GLP but not sufficiently documented
Justification for type of information:
Guideline method conducted in a reliable laboratory but without sufficient GLP documentation
Qualifier:
according to guideline
Guideline:
other: US Dept. of Transporation (DOT) 49 CFR 173.136-7, 1994
Principles of method if other than guideline:
Occlusive exposure of rabbits to test material for 3 m, 60 m or 4 h.
GLP compliance:
yes
Remarks:
signature of QA officer but no statement available.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm
- Age at study initiation:
- Weight at study initiation:
- Housing:singly in suspended stainless steel cages with mesh floors.
- Diet (e.g. ad libitum): ad libitum, Purina Rabbit Chow 5326
- Water (e.g. ad libitum): ad libitum, municiple tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: December 1999 To: January 21, 2000
Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
Oster A5-small
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
0-3 minutes, from 3 - 60 minutes, from 60 minutes to 4 hours.
Observation period:
1 h after patch removal. For the 4 hour time point, subsequent evaluations were performed approximately 24, 48 and 72 h after removal of the 4 h patch.
Number of animals:
3 per time point
Details on study design:
The dorsal area of each rabbit's trunk was clipped free of fur; each was examined for evidence of pre-test skin irritation. Three test sites, each approximately 6 cm2, were delineated on each rabbit. Five-tenths of a ml of the test stubstance was applied to each of the sites on each animal and covered with a 1 in x 1 in 4-ply gauze pad. The torso of each was wrapped with 3-in Micropore tape and Elizabethan collars were placed on each rabbit and they were returned to their cages. The collars were removed after 4 h.

The patches were removed at the appropriate intervals (3 minutes, 1 hour and 4 hours). The sites were gently wiped with water and a clean towel to remove any residual test substance. All sites were evaluated for corrosion 1 h after patch removal. Subsequent evaluations were performed approximately 24, 48 and 72 h after removal of the 4 h patch.

Corrosion was considered to have resulted if the test substance caused full-thickness necrosis (or ulceration) at the test site in at least 1 animal. Full-thickness necrosis is defined as moderate to severe tissue destruction with well-defined dark brown or black discoloration and/or stiffened texture, covering a substantial area. Epidermal sloughing, erythema edema or fissuring were not considered tissue destruction. The test sites were also evaluated for skin irritation according to the Draize score system.
Irritation parameter:
other: corrosion
Basis:
mean
Time point:
other: 3 minutes, 60 minutes, 4 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: not corrosive
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
10 d
Score:
0.3
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
10 d
Score:
0
Max. score:
8
Reversibility:
fully reversible within: 10 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No sign of dermal corrosion was noted at any of the treated sites. The test substance is considered non-corrosive as applied.
Some irritation was noted in all animals, persisting through day 10. By day 14, the irritation was reversed. The conclusion is moderate irritation.
Other effects:
3-minute exposure: One hour after patch removal, very slight edema and/or erythema were observed in 2 of 3 animals. By the 24-h evaluation mark, very slight and/or very slight to well-defined erythema were noted at all 3 sites. The incidence and severity decreased with time and cleared by day 7. Desquamation was evident in one animal between days 7-10, when the site cleared.
1-hour exposure: One hour after patch removal, very slight edema and/or erythema were observed in all 3 animals. By the 24-h evaluation mark, very slight to well-defined edema and erythema were noted at all 3 sites. The incidence and severity decreased with time and cleared by day 7. Desquamation was evident in one animal between days 7-10, when the site cleared.
4-hour exposure: One hour after patch removal, very slight edema and/or erythema were observed in all 3 animals. By the 24-h evaluation mark, very slight to well-defined edema and well-defined erythema were noted at all 3 sites. The incidence and severity decreased with time and desquamation was evident in one animal between days 7-14, when the site cleared.

The highest value for erythema and edema were observed in the group having the 4 hour exposure, where the PDII was 3.7 of 8, considered by the study directors to be moderately irritating.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The skin corrosion and irritation potential of the test substance was examined in rabbits in a guideline skin corrosion study in rabbits. The neat substance is not corrosive to the skin at exposure times up to 4 hours. A 4-hour exposure was found to be moderately irritating to the skin, likely due to the contribution of an additive known to cause skin corrosion (Category 1C) and severe eye damage (Category 1) These effects resolved within 10-14 days after exposure.
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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1991 May-June
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The analogue approach is used for the hazard assessment of toxicological endpoints for the registration of the target substance pentaerythritol ricinoleate (CAS 78-22-8) based on generation of different breakdown/metabolic products, resulting not only in similar physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2015), but also consequently in similar physico-chemical and toxicological properties. The source compounds for read-across are fatty acids, C16-18, esters with pentaerythritol (CAS 85116-93-4) and trimethololpropane ricinoleate (CAS 67025-99-4). It is proposed that the different alcohols resulting from ester hydrolysis of the source compounds and the target substance will not result in significant variation in biological effects.
Neither target nor source compounds are classified for mammalian hazardous effects. The use of reliable experimental data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is adequate for the purposes of fulfilling the data requirements of registration and classifying potential hazards. Similar grouping into categories has been accepted by other regulatory agencies (U.S. EPA, 2010; U.S. FDA for food notifications). Thus, this read-across approach is adequate for the purposes of risk assessment and classification and labeling.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
Henkel, 51531022
- Expiration date of the lot/batch: 1992 July 25
- Purity test date: 1991 January 25

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable up to 18 months
- Solubility and stability of the test substance in the solvent/vehicle:
Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
N/A
- Final dilution of a dissolved solid, stock liquid or gel:
Test substance was suspending in Tween 80 (1:1 ratio), heated to 70 °C, and diluted with distilled water to desired concentration
Species:
rabbit
Strain:
other: Kleinrussen
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach/D.
- Age at study initiation: 4 months
- Weight at study initiation: 2090 g
- Housing: single cages
- Diet (e.g. ad libitum): ad libitum Ssniff rabbit diet K4, Ssniff GmbH, Soest/D.
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature, 20-25 °C
- Humidity (%): 45-70%
- Photoperiod (hrs dark / hrs light): 12 hrs
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
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): warm water
- Time after start of exposure: 24 hours

SCORING SYSTEM: Cornea opacity (0-4), Iris (0-2), Conjunctivae redness (0-3), Conjunctivae chemosis (0-4), Exsudation (0-3)

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
other: exsudation
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
1
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was evaluated for eye irritation under OECD guideline 405. The test substance did not cause eye irritation in rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An in vivo skin corrosion study was performed in 3 rabbits according to a U.S. Transportation guideline. The test demonstrated that the substance was noncorrosive and moderately irritating under occlusive wrappings. The irritation effect was attributed to an additive in this mixture which is known to be a corrosive substance. Overall, the PE esters of fatty acids are not known to be dermal irritants (Becker, et al., 2015 on Pentaerythrityl Tetraesters; U.S. EPA Screening Level Hazard Characterization on Polyol Esters Category, 2011), due in part to the low bioavailability via the dermal route.

An eye irritation study demonstrated that an anlogue substance was not irritating.

Justification for classification or non-classification

The skin irritation (study under more severe conditions than currently required) showed skin irritation attributed to a corrosive additive. The ester itself is not considered irritating to the skin. No irritation was seen in studies of exposure to the eye. The criteria for classification according to Regulation EC no. 1272/2008 are not met.