Registration Dossier

Administrative data

Description of key information

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 vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study under GLP
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, 28 July 2015.
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
“In vitro Skin Irritation: Reconstructed Human Epidermis Test Method”. 06-Jul-2012.
Qualifier:
according to
Guideline:
other: In Vitro EpiDermTM Skin Irritation Test (EPI-200-SIT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm (EPI-200-SIT)
Version / remarks:
07-Nov-2014
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
The substance was stored at room temperature. The test substance appeared as a cream to tan solid. The expiration date of the test substance was 17 May 2020.
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: Not specified
Justification for test system used:
This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
Vehicle:
unchanged (no vehicle)
Details on test system:
The test will be carried out with the reconstituted three-dimensional human skin model EpiDerm (MatTek). This skin model consists of normal human epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis. The NHEK are cultured on chemically modified, collagen-coated cell culture inserts (Millicell). The EpiDerm epidermis model exhibits in vivo-like morphological and growth characteristics which are uniform and highly reproducible. It consists of organised basal, spinous and granular layers and a multi-layered stratum corneum analogous to patterns found in vivo.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
- Amount(s) applied (volume or weight with unit): 25 mg

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL
- Concentration (if solution): 5%
Duration of treatment / exposure:
95 minutes (30 minutes in 37 degrees C, 60 minutes under sterile flow)
Duration of post-treatment incubation (if applicable):
24 h
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Value:
113.4
Vehicle controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was evaluated for skin irritation potential by assessing its effect on a reconstituted three-dimensional human epidermis model using MTT reduction as an indication of tissue viability. The test substance was observed to be non-irritating at doses up to 10 mg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Remarks:
done in 1984 prior to 2008 and amending regulations
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1984-10-02 to 1984-10-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Complete guideline conform study report available. Study is performed under GLP.
Justification for type of information:
The analogue approach is used for the hazard assessment of toxicological, eco-toxicological and environmental fate endpoints for the registration Pentamid™ KH (EC 934-047-1). The hypothesis is that data can be read-across between Pentamid™ KH and its structural analogues, based on structural similarity and common breakdown/metabolic products (Scenario 1 of the Read-Across Assessment Framework (RAAF, ECHA, 2015)).

For mammalian toxicity the “parent” substances show no significant systemic or dermal toxicity in mammals and vertebrates. One of the metabolic products of Pentamid™ KH, the well-studied terephthalic acid, has no significant systemic toxicity. The amine metabolite, however, shows diffuse mammalian systemic toxicity at moderate concentrations. This metabolite is employed in the risk assessment, in agreement with the European Union draft Risk Assessment Report of 2008.

The sole classification for Pentamid™ KH is the precautionary aquatic chronic 4 category, based on low water solubility and a log Kow higher than 4.

Read-across data, all evaluated as reliable according to Klimisch scores of 1 or 2, to estimate the toxicity of the registered substance is used for fulfilling the data requirements of the REACH registration and classifying potential hazards. This read-across approach is adequate for the purposes of risk assessment and classification and labeling.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
other: 0.9 % polyethyleneglycol
Controls:
not required
Amount / concentration applied:
100 mg test substance moistened with 0.3 mL 0.9 % polyethyleneglycol
Duration of treatment / exposure:
24 hours after application of the test substance into the conjuctival sac of the left eye, the eyes were washed out with lukewarm physiological saline.
Observation period (in vivo):
1, 24, 48 and 72 hours
Duration of post- treatment incubation (in vitro):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Draize method used for scoring of eye irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0.7
Max. score:
10
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
0.1
Max. score:
10
Reversibility:
fully reversible within: 48 h
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this guideline OECD 405 test and the results obtained, it is concluded that the source analogue substance is not irritating to the eyes. The target substance is not classified for eye irritation according to Regulation EC No. 1272/2008.
Executive summary:

In order to assess the eye irritating potential of the test substance, 100 mg of

the source substance moistened with 0.3 mL of 0.9 % polyethyleneglycol was applied

into the conjunctival sac of the left eye of each of 3 rabbits. The untreated eye

served as control. After 24 hours the treated eye was washed. The assessment

of possible effects to the eyes was performed with the assistance of a lamp 60

minutes, 24, 48 and 72 hours after application of test item. The eye reactions

were assessed according to the numerical scoring system (acc. to Draize). The

description of the degree and nature of irritation and the presence of serious

damage were noted as follows:

- No mortality or signs of systemic toxicity occurred.

- Hyperemia was observed in all three animals at the one hour and 24 hour time

point with a maximum score of 2. This effect was still observed in one animal

with a score of 1 at the 48 hour time point (mean score 0.7 - 1 - 0.3). This effect

was reversible within 72 hours.

- Chemosis of the conjunctiva was observed in two animals one hour (maximal

score 2) and in one animal 24 hours after application (mean score 0 - 0.3 - 0).

This effect was reversible within 48 hours.

- No corneal opacity were observed in all three animals 24, 48 and 72 hours

after application of the test substance (mean score 0-0-0).

- No effects at Iris was observed in all animals 24, 48 and 72 hours after

application of the test substance (mean score 0-0-0).

Under the conditions of this test and the results obtained, it is concluded, that

the source test substance is not an irritant to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The substance was tested in an in vitro dermal irritation study (EpiDerm) and found to be non-irritating (not classified). A close structural analogue was tested in vivo in an OECD 405 compliant study, with a finding of not irritating. The criteria for classification according to Regulation EC No. 1272/2008 are not met.