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Diss Factsheets

Administrative data

Description of key information

Skin irritation (rabbit): not irritating [report, Schüngel 2004]


Skin irritation (in vitro): not irritating [report, Vohr 2004]



Eye irritation (rabbit): not irritating [report, Schüngel 2004]

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:
September to November 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: female
- Source: Charles River, 88353 Kißlegg, Germany
- Age at study initiation: not specified
- Weight at study initiation: 3.5-3.8 kg
- Housing: individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettemnaier & Siihne, 73479 Ellwangen-Holzmiihle, Gennany). The wood granulate was changed at least twice weekly.
- Diet: ad libitum, standard diet “Ssniff K-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 60 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: test substance moistened with aqua p.i.
Controls:
other: the contralateral untreated skin area served as control
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 2.5 cm x 2.5 cm
- Type of wrap if used: gauze patch, non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: exposed skin area was carefully washed with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD guideline
Irritation parameter:
erythema score
Basis:
animal: #1 to #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal: #1 to #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Other effects:
No systemic intolerance reactions were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
In a dermal irritation/corrosion study according to OECD TG 404 the test substance was applied under semiocclusive dressings for 4 hours to the shaved skin of 3 female rabbits. Skin irritation was assessed after 1, 24, 48 and 72 hours as described in the OECD guideline. The mean irritation indices for erythema and edema were 0 of max. 4. No systemic intolerance reactions were observed.
Executive summary:

In a primary dermal irritation study according to OECD TG 404 (24 April 2002), three young adult female New Zealand White rabbits were dermally exposed to 0.5 mg/ animal of Picolinamid phenylether moistened with Aqua p.i. for 4 hours. Animals then were observed for 14 days. Irritation was scored by the method described in the OECD test guideline.


No local irritations were observed. In this study, the test item is not a dermal irritant.


 

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:
September to November 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: female
- Source: Charles River, 88353 Kißlegg, Germany
- Age at study initiation: not specified
- Weight at study initiation: 3.0-3.8 kg
- Housing: individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettemnaier & Söhne, 73479 Ellwangen-Holzmühle, Germany). The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages.
- Diet: ad libitum, standard diet “Ssniff K-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day.
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 55 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: the eye, which remained untreated, served as control
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
test substance remained in the eye (eye was not rinsed) until 1 h after instillation, the eyes were rinsed with saline 1 h following instillation.
Observation period (in vivo):
1, 24, 48 and 72 hours after instillation
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 1h after instillation with physiological saline
- Time after start of exposure: 1 h

SCORING SYSTEM: according to Draize et al.

TOOL USED TO ASSESS SCORE: fluorescein, 24 h after application, the eyes were treated with fluorescein and examined. If changes were observed additional fluorescein tests were performed on day 7, 14 and 21 until the changes observed had completely subsided, however for not more than 21 days after application.
Irritation parameter:
cornea opacity score
Basis:
animal: #1,2,3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
iris score
Basis:
animal: #1,2,3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
chemosis score
Basis:
animal: #1,2,3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
conjunctivae score
Basis:
animal: #1,3
Time point:
24/48/72 h
Score:
0 - 1
Max. score:
3
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: mean score after 72 hours: 0.3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritant / corrosive response data:
Redness of conjunctivae (grade 1) was observed in all animals 1 hour after instillation. The fluorescein test performed after 24 hours revealed no corneal effects.
Other effects:
No systemic intolerance reactions were observed.










































































































































































































































































































































Irritant effects on the eye



 



Animal 1, Body Weight 3715 g



 



 



 



 



 



 



 



Observation



1h



24h



48h



72h



day 7



day 14



day 21



Degree of cornea opacity



0



0



0



0



-



-



-



Area of cornea opacity



0



0



0



0



-



-



-



Fluorescein-degree



#



0



#



#



-



-



-



Coloration area



#



0



#



#



-



-



-



Iris



0



0



0



0



-



-



-



Redness conjunctivae



1



1



0



0



-



-



-



Chemosis conjunctivae



0



0



0



0



-



-



-



 



 



 



 



 



 



 



 



Animal 2, Body Weight 3792 g



 



 



 



 



 



 



 



Observation



1h



24h



48h



72h



day 7



day 14



day 21



Degree of cornea opacity



0



0



0



0



-



-



-



Area of cornea opacity



0



0



0



0



-



-



-



Fluorescein-degree



#



0



#



#



-



-



-



Coloration area



#



0



#



#



-



-



-



Iris



0



0



0



0



-



-



-



Redness conjunctivae



1



0



0



0



-



-



-



Chemosis conjunctivae



0



0



0



0



-



-



-



 



 



 



 



 



 



 



 



Animal 3, Body Weight 2999 g



 



 



 



 



 



 



 



Observation



1h



24h



48h



72h



day 7



day 14



day 21



Degree of cornea opacity



0



0



0



0



-



-



-



Area of cornea opacity



0



0



0



0



-



-



-



Fluorescein-degree



#



0



#



#



-



-



-



Coloration area



#



0



#



#



-



-



-



Iris



0



0



0



0



-



-



-



Redness conjunctivae



1



1



0



0



-



-



-



Chemosis conjunctivae



0



0



0



0



-



-



-



-: no further examination



#: no examination



Animal 1



day 1-3:



Soft feces



 



Animal 2



day 2 and 3:



soft feces



 



day 1 and 2



reduced food intake



 



day 1



reduced water intake



Animal 3



day 2 and 3



redcued food intake


Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 female rabbits. Eye irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. In this study Picolinamid-Phenylether shows very slight irritant effects (mean irritation index for conjunctivae score = 0.3 of max. 3) which were fully reversible within 2 days. No irritation effects were registered for cornea, iris and conjunctival chemosis up to 72 hours after instillation. The weight of these evidences indicates that the test substance may be considered as "slightly irritating to the eyes". No systemic intolerance reactions were observed.

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mg of Picolinamid-phenylether was instilled into the conjunctival sac of one eye of 3 young adult female New Zealand White rabbits (3/sex) and the animals were observed for 21 days. The eyes were not washed until 1h after instillation, thereafter washing was performed with physiological saline. Irritation was scored by the method of Draize.


 


A single application of the test substance into the conjunctival sac provoked slight irritation of the conjunctiva in one animal which lasted up to 2 h after application. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters corneal opacity, iris score, chemosis score and conjunctivae score. In this study, the test item is not an eye irritant.

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 primary dermal irritation study according to OECD TG 404 (24 April 2002), three young adult female New Zealand White rabbits were dermally exposed to 0.5 mg/ animal of Picolinamid phenylether moistened with Aqua p.i. for 4 hours. Animals then were observed for 14 days. Irritation was scored by the method described in the OECD test guideline.


No local irritations were observed. In this study, the test item is not a dermal irritant.


 


In a dermal irritation study performed in accordance with OECD Guideline 431 (In Vitro Skin Irritation) (originally adopted 13 April, 2004), Picolinamid phenylether was applied to 3D human epidermis model tissue (EST-100) for an exposure period of 3 to 60 minutes in triplicates. 25µg of test substance were topically applied to the epidermal surface and moistened with physiological saline in order to improve further contact between the solid and the epidermis. The test item was spread to match the surface of the tissue.


After 3 minutes exposure at room temperature and 1 hours at 37°C in an incubator with 5 % CO2, in a > 95% humidified atmosphere, the tissues were washed with phosphate buffered saline to remove any residual test material. Subsequently the tissue constructs were incubated for 2h at 37°C with MTT solution. MTT solution (1 mL/well) was added to each well below and above the skin units. Cytotoxicity (corrosivity) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.


The negative (physiological saline) control gave responses that were within the acceptance criteria and as such demonstrated the validity of the study.


The relative mean tissue viability obtained after 3 minutes treatment with Picolinamid phenylether compared to the negative control tissues was 103.72%, after the 1 hour treatment period the treatment versus control value was 93.25%. Since the mean relative tissue viability for the test substance was above 50%, Picolinamid phenylether is identified to be not corrosive.


Eye irritation 


In a primary eye irritation study similar to OECD TG 405, 0.1 mg of Picolinamid-phenylether was instilled into the conjunctival sac of one eye of 3 young adult female New Zealand White rabbits (3/sex) and the animals were observed for 21 days. The eyes were not washed until 1h after instillation, thereafter washing was performed with physiological saline. Irritation was scored by the method of Draize.


 


A single application of the test substance into the conjunctival sac provoked slight irritation of the conjunctiva in one animal which lasted up to 2 h after application. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters corneal opacity, iris score, chemosis score and conjunctivae score. In this study, the test item is not an eye irritant.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not warranted.