Registration Dossier

Administrative data

Description of key information

The test substance is 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
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
A total of 10 subjects, 2 male and 8 female, were placed on the test. Patches were used occlusively. Approximately 0.2 mL test material was applied to each patch. On day one, subjects were patched with duplicate patches on each volar forearm for 24 hours. On day 2 to 4 the arms were scored.
GLP compliance:
no
Specific details on test material used for the study:
- Description: clear liquid
Species:
other: human
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.2 mL
Duration of treatment / exposure:
24 hours
Observation period:
96 hours
Details on study design:
- Panel Selection: A total of 10 subjects, 2 male and 8 female, were placed on test. Subjects range in age from 27 to 59: 1 subject is 27 to 30; 4 subjects are 31 to 45; 5 subjects are 46 to 59. Legally valid written informed consent, in conformity with Fed. Reg. 21 CFR 50.20 - 50.25, February 9, 1981, effective July 27, 1981, pp. 7687-7689: "Reference for Elements of Informed Consent" vas secured from each subject. Each subject was assigned a permanent HRL Identification Number. Each subject completed an HRL History Form, including relevant medical history. No subject was used if he or she exhibited any dermatological or other medical or physical condition which would preclude topical application of the test material. No known pregnant nor nursing women were used on this panel. At: least six weeks elapsed since a subject was patched in a Repeated Insult Patch Test or a Photoallergy test before he or she was used in this Phototoxicity test.
- Light Source: UV-A irradiation was from four F40BL fluorescent tubes with an output at 360 nm of approximately 1.23W per 10nm of wave-length. These lamps deliver a dose of approximately 0.22 J/cm2/min at a distance of 10 cm (the distance from the lamp to the skin sites) as measured with the International Light, Inc, IL443 Phototherapy System including IL443 radiometer S/N 1108, with UV-A Phototherapy Sensor, consisting of: SEE115 Detector S/N 1125, UV-A Filter S/N 704, W Diffuser S/N 1819 for cosine spatial response and IPIR calibration.
- Patch Preparation: The Readi-Bandage (Professional Medical Products) patch was used occlusively. Approximately 0.2 mL was applied to each patch. The volar forearms were the patch sites. Patches were applied starting proximal (closest to the elbow fold) to distal (closest to the wrist) One arm was patched with the test material; because the dosage of UV-A irradiation is not erythrogenic, no "control" site is delineated on the forearm rather, the entire forearm serves as an irradiation "control" for the irradiated site to which the test material was applied. The other arm was patched with the test material, but not irradiated. (The nonirradiated arm was protected from the light source either by the subject's own long sleeve or the special HRL "mitten") The right forearm was the irradiated arm for odd-numbered subjects; the left forearm was the irradiated arm for even-numbered subjects. (Subjects were cautioned to protect the non-irradiated arm from exposure to sunlight throughout the test period.)
- Patching Schedule
-- Day One: Subjects were patched with duplicate patches on each volar forearm. The test sites were marked with gentian violet. The subjects were then instructed to keep the patches dry. Patches were worn for 24 hr.
-- Day Two: Subjects returned to HRL. The HRL Project Manager removed the patches, read the sites and recorded the scores of the patch sites of both arms. The designated forearm was irradiated and scored immediately after irradiation. (The subject's non-irradiated arm was protected from the light source either by the subject's own long sleeve or, the special HRL arm "mitten".) The test sites were re-marked with gentian violet. Subjects were reinstructed to protect both arms from ultraviolet irradiation throughout the test period.
-- Day Three: Subjects returned to HRL. The HRL Project Manager read and recorded the scores of the test sites of both arms. The gentian violet marks were renewed if necessary.
-- Day Four: Subjects returned to HRL. The HRL Project Manager read and recorded the scores of the test sites of both arms. If a 2-level or greater reaction was not observed at any site, the Phototoxicity Test was deemed complete, except that each subject was instructed to report to HRL any delayed reaction experienced.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Irritant / corrosive response data:
A total of 10 subjects, 2 male and 8 female, completed the test. No reactions were exhibited on the irradiated or non-irradiated sites.
Interpretation of results:
GHS criteria not met
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
- Description: White, crystalline solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, The Netherlands
- Weight at study initiation: 2500 - 3500 g
- Housing: Individually in suspended, galvanized cages, fitted with wire-mesh floor and front
- Diet: Standard laboratory rabbit diet, ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±3
- Humidity (%): 40-70
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The other untreated eye
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
7 days
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
The eyes of the rabbits were examined 24 hours prior to testing and only those animals without observable eye defects were used. 0.1 g of the undiluted test material was allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower lid were then carefully closed and subsequently held together for about 1 second. The eyes were not washed out following administration. Ocular reactions were judged using the scoring scale from OECD guideline 405. Eye effects were examined 1 hour, 24, 48, 72 hours and 7 days.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
After one hour the eye effects observed in all three rabbits consisted of moderate redness and swelling of the conjunctivae. During the 7-day observation period these eye effects cleared partly or completely. After 7 days, only slight redness of the conjunctivae was observed in 2 out of 3 rabbits. On the basis of observations in earlier experiments with comparable effects it is expected that these effects are fully reversible.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a study by Harrison (1986), the potential of the test material to induce a phototoxic response was determined. A total of 10 subjects, 2 male and 8 female, were used in the test. Approximately 0.2 mL of the test material was applied to each patch on the volar forearms under occusive conditions for 24 hours. One arm was patched with the test material and irridiated after 24 hours and the the other forearm was patched with the test material, but not irradiated. The skin was scored 24, 48, and 72 hours after removal of the patch for edema and erythema. No erythema or edema was observed in the irridiated and control sites in any of the subjects. Therefore it can be concluded that the test substance is not irritating to the skin.

Eye irritation

In a GLP-compliant eye irritation study, performed in accordance with OECD Guideline 405, three New Zealand rabbits were exposed to the test substance. 0.1 g undiluted test substance was inserted in one eye of each rabbit. To prevent loss of test material, the eyes of the rabbits were carefully closed for 1 second. After 1, 24, 48, 72 hours and 7 days, the eyes were judged based on the scoring system described in the OECD guideline. After one hour the eye effects observed in all three rabbits consisted of moderate redness and swelling of the conjunctivae. During the 7-day observation period these eye effects cleared partly or completely. After 7 days, only slight redness of the conjunctivae was observed in 2 out of 3 rabbits. On the basis of observations in earlier experiments with comparable effects it is expected that these effects are fully reversible. Based on the results, it can be concluded that the test substance is not an eye irritant

Justification for classification or non-classification

The test substance does not have to be classified for skin or eye irritation according to Regulation (EC) No 1272/2008.