Registration Dossier

Administrative data

Description of key information

The test substance was considered to be irritating to the skin.

Based on the observed irreversibility of the effects, the test substance was considered to cause irreversible damage to the 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:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Qualifier:
according to
Guideline:
other: MAFF Testing Guideline of 12 Nousan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany
Specific details on test material used for the study:
- Name of test substance: PVP-Iod 30/06- Test substance No.: 04/0282-1- Batch No.: G2295BPZO- Date of production: October 15, 2002- Physical state/appearance: solid brown- Purity: 97.2 g/100g- Storage: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS - Source: Centre Lago S.A., 01540 Vonnas, France - Age at study initiation: 5-6 months - Weight at study initiation: 3.31 – 3.45 kg - Housing: single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2 - Diet: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day) - Water: tap water, ad libitum - Acclimation period: at least 5 days ENVIRONMENTAL CONDITIONS - Temperature (°C): 20 - 24 - Humidity (%): 30 - 70 - Air: fully air-conditioned - Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE- Area of exposure: A test patch (2.5 cm x 2.5 cm) on the dorsolateral part of the trunk- Type of wrap if used: the test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixornullo stretch (adhesive fleece), Beiersdorf AG REMOVAL OF TEST SUBSTANCE - Washing: the test substance was removed with Lutrol® (Lutrol® E 400 = Polyethylenglycol, BASF Aktiengesellschaft) and Lutrol®/water (1:1) - Time after start of exposure: 4 hoursOBSERVATION TIME POINTSImmediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.SCORING SYSTEM:For evaluation, the calculation of the mean values of erythema and edema for readings at 24, 48 and 72 hours were quoted . Additionally, the reversibility of the observed findings was taken into account. The evaluation is based on the criteria of Annex V1 of the Commission Directive 67/548/EEC.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
- At removal of the bandage it was observed that the minimally moistened test substance had hardened and the patch firmly sticked to the application site. After removal of the patch, which was only possible by employing enforced mechanical pull, the application area was washed off.- Moderate or marked erythema (grade 2 or 3) was observed in almost all animals immediately after removal of the patch up to study termination on day 14. Severe erythema (grade 4) and slight edema (grade 1) as well as petechiae were noted in one animal from 24 up to 72 hours.- Mechanical skin lesions due to the adhesive test substance and yellow discolored application area were noted in all animals during the observation period.- Thickening of the skin of the application area was observed in all animals at study termination on day 14. Some cutaneous findings, which were at least partly induced by the adhesion of the test substance to the skin and the mechanical force for removal of the test patch, were still present in all animals 14 days after removal of the patch.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to
Guideline:
other: MAFF Testing Guideline of 12 Nousan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany
Specific details on test material used for the study:
- Name substance: PVP-Iod 30/06- Test substance No.: 04/0282-1- Batch-No: Lot: G2295BPZO- Date of production: 15 Oct 2002- Purity: 97.2 g/100g- Storage conditions: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Centre Lago S.A., 01540 Vonnas, France- Age at study initiation: about 5 months- Weight at study initiation: 3.54 – 3.66 kg- Housing: single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2- Diet: Kliba-Labordiät (Kaninchen & Meerschweinchen-haltung „GLP“), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)- Water: tap water ad libitum- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 24- Humidity (%):30 - 70- Air: fully air-conditioned- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL bulk volume (about 33 mg of the comminuted test substance) was applied to the conjunctival say of the right eyelid
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
28 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE - Washing: the treated eye was rinsed with 3 to 6 mL of hand warm tap water for 1 tot 2 minutes using a syringe with a blunt probe - Time after start of exposure: 1 hour SCORING SYSTEM: Readings were performed approx. 1, 24, 48 and 72 h after application and then in weekly intervals maximally up to day 28. For evaluation, the calculation of the mean values of corneal opacity, iris, conjunctival redness and chemosis for readings 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account . The evaluation is based on the criteria of Annex VI of the Commission Directive 67/548/EEC that were in place on the date of report TOOL USED TO ASSESS SCORE: daylight tubes “Lumilux” (L 58W/860 PLUS ECO 25x1, Osram, Germany)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 28 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 28 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Slight corneal opacity (grade 1) was observed in all animals 24 hours after application and persisted up to 48 or 72 hours in one animal each. In one of these animals slight corneal opacity was again noted on day 14 only. In the third animal slight corneal opacity increased to moderate (grade 2) at the 48-hour reading up to day 7 and increased to marked (grade 3) on day 14 up to day 28 (study termination). Moderate iritis (grade 1) was observed in all animals 24 hours after application and persisted in one animal up to 48 hours and in two animals until 72 hours. Moderate or severe conjunctival redness (grade 2 or 3) were noted in all animals from 1 hour up to 72 hours after application. Slight or moderate conjunctival redness (grade 1 or 2) were observed in all animals on day 7 and in two animals on day 14. Moderate conjunctival redness decreased to slight in one animal after 21 days. Moderate or marked conjunctival chemosis (grade 2 or 3), noted in all animals 1 hour after application up to 72 hours, decreased to slight (grade 1) in one animal on day 7. Slight conjunctival chemosis persisted in one animal up to day 14 Slight to severe discharge (grade 1 to 3) was noted in all animals 1 hour after application up to 48 hours and in two animals up to 72 hours. Additional findings like small retraction in the eyelid, suppuration, contracted pupil, discharge of blood, loss of corneal tissue, marginal vascularization of the cornea in a circumscribed area as well as vascularization into the central part of the cornea in a circumscribed area and injected scleral vessels in a circumscribed area or circular were noted during the observation period. In two animals the ocular reactions were reversible within 14 or 28 days after application. The ocular reactions were not reversible in one animal within 28 days after application. Marked corneal opacity (area involved > ¼ < ½ circular, in the central part of the eye), small retraction in the eyelid, contracted pupil, injected scleral vessels in a circumscribed area and vascularization into the central part of the cornea in a circumscribed area (about half of the eye) were still observed in this animal at study termination on day 28.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a GLP compliant study (2005), in accordance with OECD guideline 404, the potential to cause acute dermal irritation or corrosion was assessed by a single topical application of an amount of 0.5 g of the test substance for 4 hours to the intact skin of three White New Zealand rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing. At removal of the bandage it was observed that the minimally moistened test substance had hardened and the patch firmly sticked to the application site. After removal of the patch, which was only possible by employing enforced mechanical pull, the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and then in weekly intervals until day 14. Moderate to severe erythema was observed in the animals during the course of the study. One animal showed slight edema from 24 up to 72 hours after removal of the patch. Mechanical skin lesions due to the adhesive test substance, yellow discolored application area and petechiae were noted during the observation period . Thickening of the skin of the application area was observed in all animals at study termination on day 14. Some cutaneous findings, which were at least partly induced by the adhesion of the test substance to the skin and the mechanical force for removal of the test patch, were still present in all animals 14 days after removal of the patch. The average score (24 to 72 hours) for irritation was calculated to be 2, 3, and 4 for erythema and 0, 0, and 1 for edema, for animal 1, 2 and 3, respectively. Considering the described cutaneous reactions as well as the average score for irritation, the test substance shows a skin irritation potential under the test conditions chosen, although the reactions were considered to be at least in part a secondary effect related to the adhesion of the test substance and the mechanical force needed for patch removal.

In a GLP compliant study (1999), in accordance with OECD guideline 404, the irritation potential of the test substance was determined by topical application of 0.5 mL to 6 cm2 intact dorsal skin of three young adult New Zealand White rabbits. After an exposure period of 4 hours under semi-occlusive conditions, the dressing was removed and the skin washed to remove the test substance. No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred . The body weight of all rabbits were considered to be within the normal range of variability. As no irritating effects were observed the erythema and edema scores were determined to be 0. The substance was considered to be not irritating.

In two studies (1985), in accordance with OECD guideline 404, the skin irritating potential was determined by subjection three Vienna White rabbits to a topical application of the test substance as a 6% aqueous solution. A test patch (2.5 cm x 2.5 cm) was wetted with the undiluted substance which was secured with a semiocclusive dressing. After an exposure period of 4 hours the test patch was removed and the application area was washed with lutrol and lutrol/water (1:1). 30 – 60 min after removal of the test patches and 24, 48 and 72 hours after application readings were performed. The difference between the two studies was the pH of the test substance. In one study it was 1.2 and in the other 4.4. As no irritating effects were observed in either study the erythema and edema scores were determined to be 0 for both studies. The substance was considered to be not irritating.

In three studies (1984) the skin irritating potential was determined by subjecting six Vienna White rabbits per test group to a topical application of the test substance as aqueous solution. A test patch was wetted with the test substance and secured with an occlusive dressing. The test site was clipped and abraded in test group 2 and only clipped for test group 1. After an exposure period of 24 hours the test patch was removed and the application area washed with water. 30 – 60 min after removal of the test patches and 48 hours, 72 hours and 8 days after application readings were performed. In these five studies, five different solutions of the test substance were tested and different locations on the flanks were tested. In a fourth study, an additional test group was added in which 6 animals were simultaneously exposed on the right and left side of the flank, in which one side was only clipped and the other clipped and abraded. In a fifth study only tests were performed with this additional test group (test group 1 and 2 were not tested). In all studies the substance was not irritating when it was tested on the intact skin. The highest measured erythema score and edema scores found was 1, but in most cases it was even 0. Slight irritating effects were observed in tests performed on the abraded skin, but the highest erythema and edemas scores found was 2. So even when the skin was abraded it would not be considered to be irritating to the skin.

In eight studies (1978) the skin irritating potential was determined by subjecting six Vienna White rabbits to a topical application of the test substance. A test patch was wetted with a 10% solution of the test substance at pH ranging from 1.7 to 4.5 and secured with an occlusive dressing. The test sites were prepared by shaving the left and the right flank of the animal. One of these flanks was abraded. Readings were performed 24 and 72 hours, and 8 days after application of the test substance. Due to staining of the skin by the test substance it was not possible to determine the erythema scores of several animals in these studies. Each of these testing solutions resulted in a similar result. Scaling was observed in all animals at the abraded skin site and in some studies in several animals at the intact skin site. The overall irritating effects observed were low, even at the abraded skin sites. Based on this information the test substance was not considered to be irritating to the skin.

In six studies (1977) the skin irritating potential was determined by subjecting two Vienna White rabbits to the substance for 1, 5, 15 minutes and 20 hours. The substance was applied to the dorsal skin by applying a piece of cloth tinctured with a 50% aq. solution of the test substance. Following the short-time application (minutes), the application site was rinsed with undiluted "Lutrol 9" and further with a 50% aq. Lutrol solution. Following the long-time application, the application site remained as it was. At 24 hours and 8 days after the start of exposure the irritating potential was determined. Due to the presence of residual substance no clear statement could be made about the irritating potencies of test substance.

The study from 2005 is the most recent study and the only for which the undiluted test substance (solid) is tested and a purity is availble. Therefore this study was selected as key and subsequently, the test substance was considered to be irritating to the skin.

The skin irritating potential is also demonstrated in an article by Liu and co-workers (2006) in which they report of a 24-year-old female who was admitted for subtotal thyroidectomy. The skin over the anterior neck was sterilized with 10% Povidone-iodine (PI) alcohol solution. After a 3-hour surgery, the patient complained of burning pain over the back at the recovery room. Physical examination revealed a 9 x 11 cm area of skin lesion partially thickened amid on the middle of the back where the PI solution accumulated. Skin tests were carried out with 70% ethanol, 10% aqueous PI and 10% alcohol solution, but there was no allergic reaction on each test. It was concluded that prolonged skin contact with large amount of PI-solution could result in skin injury.

Eye irritation

In a GLP compliant study (2005), in accordance with OECD guideline 405, the eye irritating potential was determined. An amount of 0.1 mL bulk volume (about 33 mg) of the test substance was applied to one eye of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About 1 hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 28. Slight to marked corneal opacity, moderate iritis, slight to severe conjunctival redness, slight to marked conjunctival chemosis and slight to severe discharge were observed in the animals during the course of the study. Additional findings like small retraction in the eyelid, suppuration, contracted pupil, discharge of blood, loss of corneal tissue, marginal vascularization of the cornea in a circumscribed area as well as vascularization into the central part of the cornea in a circumscribed area and injected scleral vessels in a circumscribed area or circular were noted during the observation period. In one animal slight corneal opacity increased to moderate (grade 2) at the 48-hour reading up to day 7 and increased to marked (grade 3) on day 14 up to day 28 (study termination). Moderate conjunctival redness decreased to slight in one animal after 21 days. The ocular reactions were not reversible in one animal within 28 days after application. Marked corneal opacity (area involved > ¼ < ½ circular, in the central part of the eye), small retraction in the eyelid, contracted pupil, injected scleral vessels in a circumscribed area and vascularization into the central part of the cornea in a circumscribed area (about half of the eye) were still observed in this animal at study termination on day 28. Mean scores calculated for each animal over 24, 48 and 72 hours were 1, 0.7 and 1.7 for corneal opacity, 0.7, 1 and 1 for iris lesions, 3, 2.3 and 3 for redness of the conjunctiva and 2, 2.3 and 2 for chemosis. Based on the observed irreversibility the test substance was considered to be severely irritating to the eyes.

In a HET-CAM test (2005) the potential of the test substance to cause serious damage to the eyes/mucous membranes was assessed by a single topical application of the undiluted test substance, and of a 10% test substance solution in doubly distilled water, to the chorionallantoic membrane (CAM) of fertilized and incubated hen eggs. Two resp. five eggs per test substance concentration were observed until unambiguous irritation reactions were detected or up to a maximum time period of 210 seconds. The chorioallantoic membrane of the four eggs treated with the 10% test substance solution in doubly distilled water did not show any irritation effects until 90 s. The 1 egg with was exposed for 210 seconds showed slight heamorrhagia (score 1 out of 3) and severe coagulation (score 3 out of 3). Additionally extra- as well as intra-vascular coagulation was observed. The unchanged test substance caused showed slight Heamorrhagia (score 1 out of 3) and moderate coagulation (score 2 out of 3). Additionally in boths eggs extra- as well as intra-vascular coagulation was observed. It should be noted, that due to severe discoloration the CAM could not be evaluated clearly after washing (undiluted test substance, only). Since there were significant differences in reactions between undiluted test substance and 10% aqueous dilution, the evaluation was considered inconclusive.

In an eye irritation/corrosion study (1999) performed according to OECD guideline 405, three (2 male, 1 female) NZW rabbits were treated with 0.1 mL of a aqueous test substance solution in the left eye. The right eyes remained untreated and served as the reference control. The treated eyes were rinsed gently with bi-distilled water approximately 24 hours after administration. The ocular reaction was assessed after 1, 24, 48 and 72 hours and after 7, 14 and 21 days. All animals displayed slight to moderate reddening (in one case persisting until day 21) and slight to marked swelling of the conjunctivae, swelling of the nictating membrane, slight mucous discharge and corneal opacity (in one case persisting until day 7, in another case until the end of the observation period). In two cases, slight to moderate watery discharge was observed. No staining of the cornea, sclera or conjunctivae by the test article was observed. No corrosion of the cornea was observed at any of the reading times. However, based on the irreversibility of the corneal opacity and the conjunctival redness observed in one animal the test substance is considered to have irreversible effects on the eye.

In two studies (1985), in accordance with OECD guideline 405), the eye irritating potential was determined. 0.1 mL of a 6% aqueous test substance solution was applied to the conjunctival sac of the right eye of three Vienna White Rabbits. The substance was not washed out. Readings were performed 24, 48, and 72 hours, and 8 days after application. The difference between the two studies was the pH of the test substance. In the first study the pH was 1.2. The mean irritating scores of this study (24-72h) were determined to be 0, 0.7, and 0 for corneal opacity, 1, 1, and 0 for iritis, 2.7, 2.3, and 0.7 for conjunctival redness, and 1.3, 1.3, and 0 for chemosis, for animal 1, 2, and 3, respectively. Small retractions were observed in the females at the following reading times: 24, 48 and 72 hours and 8 days after application. Additionally, in one female at reading time 72 hours after application pupil contraction was observed. In the second study the pH was 4.4. The mean irritating scores of this study (24-72h) were determined to be 0, 0, and 0 for corneal opacity, 0, 0, and 0 for iritis, 1.3, 1, and 2 for conjunctival redness, and 0, 0, and 1 for chemosis, for animal 1, 2, and 3, respectively. Based on the information the test substance was considered to be irritating to the eyes if the pH of the test substance is 1.2.

 

In an additional four very similarly performed eye irritation/corrosion studies (1978) the test substance was evaluated when applied as a 1% aqueous Polyvinylpyrrolidone-iodine solution. Each study consisted of 6 Vienna White animals. The test substance was applied to the conjunctival sac of the right eye of each animal. Then the eyelid was gently held together for 1 second. The treated eyes were not washed out. The left eye remained untreated and served as reference control. Signs of eye irritation were recorded for 8 days following administration. Based on the results obtained in these four studies, a 1 % aqueous solution of the test substance was considered to be not irritating to the eyes.

In six studies (1977, 1976) the eye irritating potential of the test substance was determined by applying 50 mg of the test substance to the conjunctival sac of the eye of two Vienna White rabbits. As a control talc was applied to the other eye of the same animal 1 and 24 hours, and 8 days after application the eyes were checked for irritating effects. Based on the information from these six studies the test substance was considered to cause irriversible damage to the eye.

Justification for classification or non-classification

Based on the available information the substance has to be classified as Skin Irrit. 2: H315: Causes skin irritation in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Based on the available information showing sustained corneal effects for more than 21 days the test substance was considered to have irreversible effects on the eye and should be classified as Eye Damage 1, H318: Causes serious eye damage, in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.