Registration Dossier

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Administrative data

Description of key information

KMPS triple salt was tested for skin irritation/corrosion and for eye irritation in a number of studies. Irreversible skin destruction after 1 h was observed in the skin irritation studies. Irreversible damage to the eye with a cornea score of 3 was determined in the eye irritation study. Thus, KMPS is considered corrosive to skin and eyes.

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:
1983-11-25 - 1983-12-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino rabbit (White Russian)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Asta-Werke AG, Bielefeld, Germany
- Age at study initiation: 16 weeks
- Weight at study initiation: 2.0 – 2.1
- Sex: females
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- 0.5 g test substance were moistened with 0.15 mL demineralised water.

Duration of treatment / exposure:
4 hours
Observation period:
Postexposure period : 14 days
Examination time points: 60 min, 24 h, 48 h, and 72 h after removal of the test patches
Number of animals:
3 animals
Details on study design:
TEST SITE
The dorsal fur was clipped. The test substance (0.5 g) was applied on dorsal skin and covered by a linen patch on an area of about 6.25 cm². The skin was divided into two areas on both sides of the spinal column of each animal. The two areas on the left side consisted of intact skin, the areas on the right side of sacrificed skin. Each side was covered by a patch. Two were for the protection of the treated skin areas and two for the untreated control area. An bandage occluded and secured the patches.

REMOVAL OF TEST SUBSTANCE
Removal of occlusive dressing after 4 hours.

SCORING SYSTEM
Numerical scoring system as given in the OECD/EU testing guidelines.

CONTROLS
The untreated skin served as control.

EXAMINATIONS
- Clinical signs: Not stated
- Dermal examination: Yes
- Other examinations: Systemic-toxic abnormalities were recorded
- No necropsy was performed in the animals
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: discolouration; eschar formation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: discolouration; eschar formation
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
Remarks on result:
other: discolouration; eschar formation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: discolouration; eschar formation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritant / corrosive response data:
ERYTHEMA: Only results of the intact skin were reported:
Grade 1 hour after exposure: 3.00
Grade 24, 48, 72 hours after exposure: 4.0

OEDEMA: Only results of the intact skin were reported:
Grade 1 hour after exposure: 1.33
Grade 24 hours after exposure: 1.00
Grade 48 hour after exposure: 0.67
Grade 72 hours after exposure: 0.00

Mean grade 24 - 72 h after exposure: 4.00 (erythema), 0.56 (oedema)

Please refer to table 1, which is presented under “Remarks on results including tables and figures”.
Other effects:
There were no systemic intolerance reactions.

Table 1: Single and means of skin reaction


 


























































































-



Hours after exposure



Skin reaction



Mean



Animal No.



1



2



3



Erythema/Scabbing



1



2



3



4



3.00



24



4



4



4



4.00



48



4



4



4



4.00



72



4



4



4



4.00



24 - 72



-



4.00



Oedema



1



2



1



1



1.33



24



1



1



1



1.00



48



1



0



1



0.67



72



0



0



0



0.00



24 - 72



-



-



-



0.56


Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). Based on Regulation 1272/2008/EC (CLP), KMPS triple salt has to be classified as corrosive to skin.
Executive summary:

Materials and methods


The skin irritating potential of KMPS triple salt was investigated in three healthy female Albino Rabbits (White Russian). A quantity of 0.5 g of moistened test material was applied to the clipped dorsal fur for a period of 4 hours under occlusive conditions. Skin readings were made 1, 24, 48 and 72 hours after removal of the occlusive dressing, and assessed for erythema and oedema. During the entire study period, animals were observed for clinical signs of toxicity and mortality.


 


Results and discussion


Clinical signs of toxicity/mortality: No systemic toxicity was stated and no mortalities occurred.


Irritation: Severe erythema were stated around the white coloured treated skin (mean score 24 - 72 h after exposure: 4.0). These erythema were irreversible within the post-exposure period of 14 days. Oedema were observed 1 hour after exposure (score 1.0 in case of two animals and 2.0 in case of one animal). Oedema were shown to be completely reversible within two days (possibly a result of the oxidising properties of the test material).


Coloration: the treated skin was white.


Corrosion: irreversible skin destruction of the treated skin were observed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no further information on the test substance (stability, purity)
GLP compliance:
no
Remarks:
Several quality assurance inspections were carried out
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: C. and J. Morton Ltd., Parsonage Farm, England
- Age at study initiation: 3 months
- Weight at study initiation: 3.42 – 3.48 kg
- Sex: Not stateD
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
- Preparation of test substance: Not stated
Duration of treatment / exposure:
Animals were sacrificed on day 2 (eyes were not rinsed throughout the entire study period).
Observation period (in vivo):
Both eyes of each animal were examined on the day before administration for signs of pre-existing irritation, reaction or abnormality which eliminate it from the study.
Ocular reactions to treatment were assessed 1 and 24 h after treatment.
Number of animals or in vitro replicates:
3 per group
Details on study design:
CONTROL
The left eye of each rabbit remained untreated and served as control.


SCORING SYSTEM:
Scoring of ocular lesions (cornea, iris, conjunctivae and chemosis) was according to grading listed in OECD guideline 405.
Additionally assessed were:
- pain response:
No response: 0 (no initial pain)
A few blinks only; normal within one or to minutes: 1 (practically no initial pain)
Rabbit blinks and tries to open eye but reflexes close it: 2 (slight initial pain)
Rabbit holds eye shut and puts pressure on lids, may rub eye with paw: 3 (moderate initial pain)
Rabbit holds eye shut vigorously, may squeal: 4 (severe initial pain)
Rabbit holds eye shut vigorously, may squeal, claw at eye and try to escape: 5 (very severe initial pain)
- ocular lesions:
Cornea
Area of cornea affected by lesion
One-quarter or less, but not zero: 1
Greater than one-quarter, less than one-half: 2
Greater than one-half, less than three-quarters: 3
Greater than three-quarters, up to whole area: 4

Conjunctivae:
Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to the lids: 2
Discharge with moistening of the lids and hairs and affecting a considerable area around the eye: 3

Interpretation of results:
A substance or preparation is considered irritant if, when applied to the eye of the animals, significant ocular lesions are caused which are present 24 h or more after instillation of the test material.
Ocular lesions are considered significant if two or more of the rabbits have mean values at or above the limit values following:
corneal opacity: 2
iris lesions: 1
redness of conjunctivae: 2.5
Chemosis: 2
(The Official Journal of the European Communities, L257/8, Vol. 26, 16/9/83 and L257/19, Vol. 26, 16/9/83)
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #1
Remarks:
12TP 677
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #2
Remarks:
12TP 678
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #3
Remarks:
12TP 680
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h .."
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
12TP 677
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
12TP 678
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
12TP 680
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
12TP 677
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
12TP 678
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
the study was terminated after 1h .."
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
12TP 680
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
the study was terminated after 1h "
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
the study was terminated after 1h "
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
animal #1
Remarks:
12TP 677
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
animal #2
Remarks:
12TP 678
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h "
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
animal #3
Remarks:
12TP 680
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h .."
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
mean
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not reversible
Remarks:
the study was terminated after 1h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
the study was terminated after 1h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
the study was terminated after 1h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
the study was terminated after 1h
Irritant / corrosive response data:
not indicated
Other effects:
not indicated

Clinical signs:


Not stated


 


Average score:


Please refer to tables 1 to 4


Cornea: Average score of all animals at 24 h was 3.0


Iris: Average score of all animals at 24 h was 0.0


Conjunctiva:Please refer to tables 2 to tables 4


Redness: Average score of all animals at 24 h was 3.0


Chemosis:Average score of all animals at 24 h was 2.7


 


Reversibility: No


Observed changes were considered to be due to necrosis, and consequently the study was terminated and the animals were killed on humane reasons 24 h after treatment.


 


Overall result:


Instillation of RD/1/85 into the conjunctival sac of three rabbits caused severe ocular lesions which were apparent in all animals within 1 h.


Principal changes included nacreous areas of opacity covering the whole of the cornea, a beefy-red appearance to the conjunctivae, marked chemosis and a creamy white ocular discharge. In addition, the lower conjunctival and nictitating membranes of all rabbits and one third of the one rabbit appeared white. It was considered that theses latter changes were due to necrosis, and consequently the study was terminated and the animals killed.


Instillation of the test material caused practically no initial pain responses in all animals.


 


Table 1: Values for ocular lesions 24 h after single ocular instillation of 0.1 g KMPS triple salt


































Animal No.



Corneal opacity



Iridial lesions



Redness of Conjunctiva



Chemosis



12TP677



3.0



0.0



3.0



3.0



12TP678



3.0



0.0



3.0



3.0



12TP680



3.0



0.0



3.0



2.0



 


Table 2:  Grades for ocular irritation responses following instillation of 0.1 g KMPS triple salt (animal 12TP 677, pain evaluation response: 1)


 













































































-



-



Grade of response at time after instillation



Region of the eye



Response



1 h



24 h



Cornea



      Opacity



3



3



"



      Area



4



4



"



      Ulceration



-



-



"



      Stippling



-



-



Iris



       Value



0



0



Conjunctiva



      Redness



1B



3



"



      Chemosis



2



3



"



      Discharge



1



3C



"



      Necrosis



-



-



"



      Ulceration



-



-



B    Lower conjunctival membranes and nictitating membrane whitened


C    Discharge white and creamy


 


Table 3:  Grades for ocular irritation responses following instillation of 0.1 g KMPS triple salt (animal 12TP 678, pain evaluation response: 1)













































































-



-



Grade of response at time after instillation



Region of the eye



Response



1 h



24 h



Cornea



      Opacity



3



3



"



      Area



3



4



"



      Ulceration



-



-



"



      Stippling



-



-



Iris



       Value



0



0



Conjunctiva



      Redness



1B



3



"



      Chemosis



2



3



"



      Discharge



1



3C



"



      Necrosis



-



-



"



      Ulceration



-



-



B    Lower conjunctival membranes and nictitating membrane whitened


C    Discharge white and creamy


 


Table 4:  Grades for ocular irritation responses following instillation of 0.1 g KMPS triple salt (animal 12TP 680, pain evaluation response: 1)













































































-



-



Grade of response at time after instillation



Region of the eye



Response



1 h



24 h



Cornea



      Opacity



4



3D



"



      Area



1



4D



"



      Ulceration



-



-



"



      Stippling



-



-



Iris



       Value



1



0



Conjunctiva



      Redness



1B



3



"



      Chemosis



2



2



"



      Discharge



1



3C



"



      Necrosis



-



-



"



      Ulceration



-



-



B    Lower conjunctival membranes and nictitating membrane whitened


C    Discharge white and creamy


D    Area white

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). Under the conditions of this test, KMPS triple salt was classified as eye damaging cat. 1 (causes severe eye damage) according to Regulation 1272/2008/EC.
Executive summary:

Materials and methods


This study was performed to assess acute eye irritation effects of KMPS triple salt in rabbits.


A quantity of 0.1 g of the test substance was instilled into the right eye of each of three healthy NZW rabbits. Ocular irritation was evaluated 1, and 24 h after instillation of the test substance.


 


Results and discussion


Please refer to tables 1 to 4, which are presented under “Remarks on results including tables and figures”.


Instillation of KMPS triple salt into the conjunctival sac of three rabbits caused severe ocular lesions which were apparent in all animals within 1 h and justified the termination of the test on humane ground, 24 h after treatment.


Principal changes included nacreous areas of opacity covering the whole of the cornea, a beefy-red appearance to the conjunctivae, marked chemosis and a creamy white ocular discharge. In addition, the lower conjunctival and nictitating membranes of all rabbits and one third of the one rabbit appeared white. It was considered that these latter changes were due to necrosis, and consequently the study was terminated and the animals killed.


Instillation of the test material caused practically no initial pain responses in all animals.


The values for ocular lesions recorded 24 h after treatment exceeded the limit values for classifying the test material as irritant to the eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/Corrosion


The skin irritating potential of KMPS triple salt was investigated in a study equivalent or similar to guideline OECD 404( Acute Dermal Irritation/Corrosion) in three healthy female Albino Rabbits (White Russian). A quantity of 0.5 g of moistened test material was applied to the clipped dorsal fur for a period of 4 hours under occlusive conditions. Skin readings were made 1, 24, 48 and 72 hours after removal of the occlusive dressing, and assessed for erythema and oedema. During the entire study period, animals were observed for clinical signs of toxicity and mortality.


Results and discussion:


Clinical signs of toxicity/mortality: No systemic toxicity was stated and no mortalities occurred.


Irritation:


Severe erythema were stated around the white coloured treated skin (mean score 24 - 72 h after exposure: 4.0). These erythema were irreversible within the post-exposure period of 14 days. Oedema were observed 1 hour after exposure (score 1.0 in case of two animals and 2.0 in case of one animal). Oedema were shown to be completely reversible within two days (possibly a result of the oxidising properties of the test material).


Coloration: the treated skin was white.


Corrosion: irreversible skin destruction of the treated skin were observed.


The available in vitro test methods (two In Vitro International Corrositex assays) allowed subcategorisation into category 1B: The mean value of the breakthrough time for all 4 vials was < 30 min.


The test substance passed through all 4 of the membranes in less than 2 hours after application. The mean value of the breakthrough time for all 4 vials was 57 minutes and 4 seconds. Under the conditions of this test, KMPS triple salt was a corrosive substance and was assigned to Packing Group II.


Furthermore, an in vitro transcutaneous electrical resistance (TER) assay is available, conforming the corrosive property. Dermal exposure to a 2.5% and 20% H-26162 aqueous dilution (w/v) using rat skin mounted in an in vitro static diffusion cell model, resulted in a 20% and 60% loss in skin integrity.


 


Eye irritation/Corrosion


A study according to OECD Guideline 405 (Acute Eye Irritation/Corrosion) was performed to assess acute eye irritation effects of KMPS triple salt in rabbits. A quantity of 0.1 g of the test substance was instilled into the right eye of each of three healthy NZW rabbits. Ocular irritation was evaluated 1, and 24 h after instillation of the test substance.


Results and discussion:


Instillation of KMPS triple salt into the conjunctival sac of three rabbits caused severe ocular lesions which were apparent in all animals within 1 h and justified the termination of the test on humane ground, 24 h after treatment. Principal changes included nacreous areas of opacity covering the whole of the cornea, a beefy-red appearance to the conjunctivae, marked chemosis and a creamy white ocular discharge. In addition, the lower conjunctival and nictitating membranes of all rabbits and one third of the one rabbit appeared white. It was considered that these latter changes were due to necrosis, and consequently the study was terminated and the animals killed. Instillation of the test material caused practically no initial pain responses in all animals. The values for ocular lesions recorded 24 h after treatment exceeded the limit values for classifying the test material as irritant to the eyes.


 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008


The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on this data, the substance is considered to be corrosive to skin (cat 1B) and eyes (cat 1) under Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.


 


Skin:


Based on the results of the skin irritation/corrosion studies (irreversible damage of the skin after 1 h) the test substance has to be classified with skin corr. cat 1B (H 314) according to CLP (GHS).


Eye:


Based on the results of the eye irritation study (irreversible damage of the eye, cornea score = 3) the test substance has to be classified with eye damage cat. 1 (H 318) according to CLP (GHS). However, since KMPS triple salt was classified as corrosive to skin and assigned H314, the risk of severe damage to eyes is considered implicit and H318 is not included in the label of KMPS triple salt.