Registration Dossier

Administrative data

Description of key information

The registration substance was investigated for skin and/or eye irritation potential in GLP conform assays according to OECD test guidelines 404 and 405. Based on the results of these studies, the test material is not a skin irritant. With regard to eye irritation, the registration substance does not fulfill the classification criteria according to the `Dangerous Substance Directive" (67/548/EEC, DSD) but is considered to be `mildly irritating to eyes` (category 2B) according to GHS-CLP.

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
Study period:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: 3 - 5 month
- Weight at study initiation:
- Housing:individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 3 days

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

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): o.5 mL per patch
- Concentration (if solution): undiluted

Duration of treatment / exposure:
4 hour exposure
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: after 4 hour exposure period

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24h / 48h / 72h
Score:
0.2
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24 h / 48h / 72h
Score:
0
Max. score:
0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the test material is not irritating to rabbit skin.
Executive summary:

The primary skin irritation potential of the registration substance was evaluated according to OECD test guideline 404 using three New Zealand albino rabbits. Only animals with intact skin were used. Each animal was treated with 0.5 mL of undiluted test material moistered with NaCl.The test item was applied over the whole surface of a 2.5 x2.5 cm cellulose patch on a piece of surgical plaster. The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage. The exposure period was 4 hours. After the exposure all remnants of the test material were carefully removed from the skin with warm tap water. Examinations of the skin took place after 30-60 minutes as well as 24, 48 and 72 hours after removal of the patches. Erythema and oedema were evaluated numerically according to the score of DRAIZE. Slight erythemas were observed in two animals up to 24 hours after removal of the plaster. Form the 48 h reading until the end of the study no signs of irritation were observed in any of the animals. The overall mean scores over all animals after 24, 48 and 72 hours were 0.2 for erythema and 0.0 for edema. Based on the study results,no relevant skin irritating potential is attributable to the registration substance in rabbits under the described test conditions.

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:
2008-06-04 till 2008-06-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline-conform study under GLP without deviations
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV
- Age at study initiation: 15 weeks (male), 15-16 weeks (females)
- Weight at study initiation: 2628 g (male), 2480 and 2803 (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum
- Acclimation period: 04-JUN-2008 to 08-JUN-2008 (one female), 04-JUN-2008 to 15-JUN -2008 (one male and one female)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours/ 12 hours

Vehicle:
unchanged (no vehicle)
Controls:
other: control area on same animal (right eye)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g per animal

Duration of treatment / exposure:
72 hrs
Observation period (in vivo):
up 7 days in the male and one female and up to 14 days in the first treated female after test item instillation.
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs; 7, 10 and 14 days
Score:
0 - 1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs; 7, 10 and 14 days
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs; 7, 10 and 14 days
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hrs; 7, 10 and 14 days
Score:
1.67 - 2
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification (Commission Directive 2001/59/EC of August 06, 2001), Hostapon TPHC is considered to be “not irritating” to the rabbit eye.
Executive summary:

The primary eye irritation potential of the registration substance was evaluated in the New Zealand albino rabbit according to OECD test guideline 405. Only animals without ocular abnormalities were used for the study. o.1 mL of undiluted test material was applied once to the conjunctival sac of the left eye of three rabbits. The untreated eyes served in each case as a control. The exposure period was 24 hours. 24 hours after instillation and at all the designated examination times at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37°C. The eyes were examined 1, 24, 48 and 72 hours as well as 7, 10 and 14 days after application of the test substance. At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01% fluorescein-sodium solution. The instillation of the test material into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment. The individual mean scores for corneal opacity was 0.67 for all three animals. The individual mean scores for the conjunctivae were 2.00 for reddening and 0.67, 0.33 and 0.67 for chemosis for each of the three animals. No abnormal findings were observed in the iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. White test item remnants were evident in the eye or conjunctival sac of one female 1 hour after instillation. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Based on the findings and in accordance with the classification criteria of Directive 67/548 EEC (DSD), the registration substance is considered to be "not irritating" to the rabbit eye. However, based on the criteria of Directive (EC) 1272/2008 (GHS-CLP) the registration substance should be considered to be "mildly irritating to eyes" (category 2B).



Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

GLP conform guideline studies are available for the evaluation of the endpoints skin irritation / corrosion and eye irritation with the pure registered substance. With regard to skin irritation/corrosion, three New Zealand albino rabbits were exposed to 0.5 mL of undiluted test material for 4 hours under semi-occlusive test conditions in accordance with OECD guideline 404. Skin reactions were assessed 30 -60 minutes, 24, 48 and 72 hours after removal of the patches. As a result, slight erythemas were observed in two animals up to 24 hours after removal of the plaster. From the 48 h reading until the end of the study no signs of irritation were observed in any of the animals. The overall mean scores over all animals after 24, 48 and 72 hours were 0.2 for erythema and 0.0 for edema. Based on the study results,no relevant skin irritating potential is attributable to the registration substance in rabbits under the described test conditions.

The primary eye irritation potential of the registration substance was evaluated in the New Zealand albino rabbit according to OECD test guideline 405. Only animals without ocular abnormalities were used for the study. o.1 mL of undiluted test material was applied once to the conjunctival sac of the left eye of three rabbits. The untreated eyes served in each case as a control. The exposure period was 24 hours. 24 hours after instillation and at all the designated examination times at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37°C. The eyes were examined 1, 24, 48 and 72 hours as well as 7, 10 and 14 days after application of the test substance. At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01% fluorescein-sodium solution.The instillation of the test material into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment.


Justification for selection of skin irritation / corrosion endpoint:
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Justification for selection of eye irritation endpoint:
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

In a guideline and GLP compliant primary skin irritation/corrosion study according to OECD TG 404, the registered substance produced only slight to moderate skin responses. Based on the individual mean scores for erythema and oedema no classification of the registered substance with regard to skin irritation/corrosion is warranted, either according to the EU Dangerous Substances Directive 67/548 (DSD) or according to the criteria of the EU Classification, Labelling and Packaging Regulation 1272/2008/EC (CLP).

With regard to primary eye irritation, a guideline and GLP conform study according to OECD TG 405 revealed individual mean scores for the conjunctivae of 2.00 for reddening and 0.67, 0.33 and 0.67 for chemosis for each of the three animals. No abnormal findings were observed in the iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Based on the findings and in accordance with the classification criteria of Directive 67/548 EEC (DSD), the registration substance is considered to be "not irritating" to the rabbit eye. However, based on the criteria of Directive (EC) 1272/2008 (GHS-CLP) the registration substance should be considered to be "mildly irritating to eyes" (category 2).