Registration Dossier

Administrative data

Description of key information

Not irritating

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: U.S. 16 CFR 1500.40
Principles of method if other than guideline:
Acute dermal toxicity test in rabbits using U.S. method dictated by 16 CFR 1500.40, similar to OECD 402.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Ten healthy NZ White rabbits were used, equally divided by sex, with body weights between 2.3 and 3.0 kg. Animals were housed individually and allowed Purina Rabbit Chow and water ad libitum.
Type of coverage:
occlusive
Preparation of test site:
other: clipped, abraded and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
2000 mg/kg bw. Using a body weight estimate of 2.5 kg, approximatley 5 g or 5 ml of test material was applied.
Duration of treatment / exposure:
24 h
Observation period:
14 days
Number of animals:
10 total, 5 males and 5 females
Details on study design:
The hair of the animals was clipped, and in 4/10 animals, the skin was abraded with epidermal incisions every 2-3 cm longitudinally over the application area. In the remaining animals, application of test material was made to intact skin. Each animal received a single dermal application of 2000 mg/kg bw. The test material was held in contact with the skin for 24 h by a heavy gauge plastic, covered with an opaque wrapping. After 24 h, the wrappings were removed and the skin gently wiped to remove any remaining test material. Animals were then observed for mortality and signs of irritation and toxicity frequently during the first day, and at least once daily thereafter for 14 days. Necropsy examinations were performed for gross organ pathology. Body weights were recorded initally and for survivors, at termination of the study.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
8
Reversibility:
fully reversible
Irritant / corrosive response data:
Erythema and edema was noted in all animals by the end of 24 h, and continued through 48 h as reflected in interim clinical notations. By 72 h, recovery had occurred and all animals were noted as "normal" on day 4. At the end of the study, all test sites were noted as "normal".
Other effects:
Diarrhea was noted in 4 of 10 animals. No lethality was observed in this study.
Interpretation of results:
other: non-irritating
Conclusions:
Irritation information on the test substance was obtained in an acute dermal toxicity study in rabbits, after a 24 hour occlusive exposure. Some skin irritation was seen between 24 and 72 h, which was fully reversible by day 4. Under the conditions of the current OECD guideline, the substance is expected to be non-irritating.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978 June - October
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Test performed by nationally accredited lab with well-defined protocol.
Qualifier:
according to
Guideline:
other: 16 CFR 1500.42
Principles of method if other than guideline:
- Principle of test: Test substance was applied to the eyes of animals for 30 seconds. The animals were observed for ocular lesions at 24, 48, and 72 hours after instillation of test material.
- Short description of test conditions: Healthy rabbits received 0.1 ml of test material in one eye. Eyes were washed with 20 ml of distilled water for 30 seconds after instillation.
- Parameters analysed / observed: Lesions to the cornea, iris, and conjunctivae. Conjunctivae were evaluated for redness and chemosis.
GLP compliance:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
NL Industries
- Expiration date of the lot/batch:
Lot # 60-8313-01
- Purity test date:
N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Not reported
- Stability under test conditions: Assumed to be stable
- Solubility and stability of the test substance in the solvent/vehicle:
N/A
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:
N/A

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
Used as received
- Preliminary purification step (if any):
None
- Final dilution of a dissolved solid, stock liquid or gel:
N/A
- Final preparation of a solid:
N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material)
: 5000 mg/kg

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)
: N/A

OTHER SPECIFICS:
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Summit View Farms, Belvidere, New Jersey, USA
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Housing: Not reported
- Diet (e.g. ad libitum): Ad libitum Purina rabbit chow
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not reported

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

IN-LIFE DATES: From: To: Not reported
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): N/A

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A
Duration of treatment / exposure:
30 s
Observation period (in vivo):
72 hr (data recorded every 24 hr)
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): With and without irrigation with distilled water
- Time after start of exposure: 30 s

SCORING SYSTEM: Lesions to the cornea, iris, and conjunctivae. For the cornea, scores ranged from 0-4, with 0 being no ulceration or opacity, and 4 being complete corneal opacity with iris not discernible. For the iris, scores ranged from 0-2, with 0 being normal, and 2 being no reaction to light, hemorrhage, gross destruction, or all of the above. Lesions to the conjunctivae were scored separately for redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris) and chemosis. For redness, scores ranged from 0-3, with 0 being normal vessels, and 3 being diffuse beefy red. For chemosis, scores ranged from 0-4, with 0 being no swelling, and 4 being swelling with lids more than half closed.

TOOL USED TO ASSESS SCORE: gross observation
Irritation parameter:
cornea opacity score
Remarks:
no wash
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
no wash
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
no wash
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
30
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Remarks:
no wash
Basis:
mean
Time point:
48 h
Score:
0.5
Max. score:
30
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
no wash
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
wash
Basis:
mean
Time point:
24 h
Score:
0.66
Max. score:
1
Irritation parameter:
cornea opacity score
Remarks:
wash
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
wash
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was evaluated under the criteria defined by 16 CFR 1500.42 for eye irritation in vivo. While the test substance was determined to be an ocular irritant by these criteria, it does not meet the criteria of Regulation EC No. 1272/2008 for classification of eye irritation.
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1963-1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
The analogue approach is used for the hazard assessment of toxicological endpoints for the registration of 2-hydroxyethyl ricinoleate (CAS 106-17-2) based on generation of different breakdown/metabolic products resulting in similar physical and biological systems (Scenario 2 of the Read-Across Assessment Framework (RAAF, ECHA, 2017). Read-across is applied from glycol stearate (CAS 111-60-4) and ethylene glycol distearate (CAS 627-83-8), and a non-hydroxyl ester, methyl ricinoleate (CAS 141-24-2). The first two of these provide hazard information on the glycol portion of the substance; the latter on the ricinoleate function. The different alcohols resulting from ester hydrolysis of the source compounds and the target substance will not result in significant variation in biological effects.

The glycol stearate was found to be non-irritating) in an experimental rabbit model as well as in human clinical studies (patch testing and evaluation over 45 days). Ethylene glycol distearate was tested in guinea pigs and found to be negative (Jones, 1984). From experimental data on the registered substance itself, it appears an extreme high dose exposure is needed to induce irritation in rabbits, which, nonetheless, was reversible (Wakatama, 1984). There is high confidence that the registered (target) substance is not irritating.

Read-across among the analogues is substantiated as valid and is adequate to fulfill the information requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Details on study design:
Draize test
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
6 total rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: mild transient irritant in 1/6
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
9 total rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
110
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
3 total rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
110
Reversibility:
not specified
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
This summary data reflects the opinion of the CIR Expert Panel that the data are valid and informative, adding to a weight of evidence demonstrating that the test substance lacks potential to be an eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The test material was evaluated for irritation potential. The test material was observed to be non-irritating to the skin and eyes. GHS criteria (Regulation EC No. 1272/2008) for classification as an irritant are not met.