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Administrative data

Description of key information

No data were available for Monuron, however key read-across in vitro studies were used from source substance Fenuron (see attached read-across justification). Skin irritation/corrosion was tested in a bottom-up approach in an EpiDerm™ artificial three-dimensional model for human skin irritation: the mean viability of cells exposed to Fenuron was 99.7%. Eye irritation/corrosion was tested in a top-down approach in a Bovine Corneal Opacity and Permeability Assay (BCOP): the in vitro Irritation Score (IVIS) was 0.285, which is below the cut-off value of 3. In conclusion, Monuron is also considered to be non-irritating/non-corrosive to skin and 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see read across justification attached to section 13
Reason / purpose:
read-across source
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
test group
Value:
99.7
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 60 min exposure, followed 42h
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Negative control (D-PBS)
Value:
100
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: 60 min exposure, followed 42h
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Positive control (5% SDS )
Value:
7.5
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: min exposure, followed 42h
Other effects / acceptance of results:
The mean optical density (OD) of 3 negative control tissues was 1.320 and was well within the acceptable range of ≥ 1.0 to ≤ 2.5.
The viability of cells treated with the positive reference item, 5% SDS, was 7.5% of the negative control and fulfilled the acceptance criterion of ≤ 20%.
The standard deviation determined for all triplicates was below the limit of acceptance of 18%. Hence, all acceptance criteria required were fulfilled.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the present test conditions, read-across test item IsoQure UR 300 tested at an exposure time of 60 minutes and a 42-hour post-treatment incubation period, was non-cytotoxic and, hence, predicted to be non-irritant to skin in an experiment employing an artificial three-dimensional model of human skin. Hence, the read-across test item did not show irritant properties and is therefore not irritating/corrosive (UN GHS no category).
Executive summary:

A key in vitro study was performed to determine cytotoxic properties of read-across test item IsoQure UR 300 to skin cells, which might lead to irritation of human skin, by using an artificial three-dimensional model of human skin. The EpiDermTM model was employed.

Three tissues were used for each treatment and concurrent control groups. The optical density (OD) was determined by using the MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, Thiazolyl blue) reduction assay and expressed as relative percentage of viability of the negative control-treated tissues. IsoQure UR 300 was applied as solid test item to the model skin surface, which was moistened with Dulbecco’s phosphate buffered saline (D-PBS).D-PBS was used as the negative control. 5% aqueous sodium dodecyl sulphate (SDS) was used as the positive reference item. An exposure time of 60 minutes was employed followed by a 42-hour post-treatment incubation period in fresh medium. The mean viability of cells exposed to IsoQure UR 300 was 99.7% of the negative controls and, hence, was well above the cut-off percentage cell viability value that distinguishes irritant from non-irritant test items of > 50%. Read-across test item IsoQure UR 300 was considered to be non-cytotoxic and predicted to be non-irritant to skin.

The mean optical density (OD) of 3 negative control tissues was 1.320 and was well within the acceptable range of ≥ 1.0 to ≤ 2.5. The viability of cells treated with the positive reference item, 5% SDS, was 7.5% of the negative control and fulfilled the acceptance criterion of ≤ 20%. The standard deviation of all triplicates determined was below the limit of acceptance of 18%.Hence, all acceptance criteria were fulfilled.

Hence,the read-across test itemdid not show severely irritant or corrosive properties andconsequently it is not classifiedfor irritation orserious eye damageaccording to UN GHS classification. The same applies to Monuron.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached read-across justification
Reason / purpose:
read-across source
Irritation parameter:
in vitro irritation score
Remarks:
mean group
Run / experiment:
240 min exposure time
Value:
0.285
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
read-across test material
Irritation parameter:
in vitro irritation score
Remarks:
cornea 7
Run / experiment:
240 min exposure time
Value:
0.41
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
read-across test material
Irritation parameter:
in vitro irritation score
Remarks:
cornea 8
Run / experiment:
240 min exposure time
Value:
0.569
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
read-across test material
Irritation parameter:
in vitro irritation score
Remarks:
cornea 9
Run / experiment:
240 min exposure time
Value:
-0.123
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
read-across test material
Irritation parameter:
in vitro irritation score
Remarks:
mean group
Run / experiment:
240 min exposure time
Value:
0.442
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
vehicle 0.9% NaCl
Irritation parameter:
in vitro irritation score
Remarks:
mean group
Run / experiment:
240 min exposure time
Value:
89.075
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Positive control 20% Imidazol
Interpretation of results:
GHS criteria not met
Conclusions:
Under the present test conditions read-across test item IsoQure UR 300 tested in the in vitro BCOP test method, had an IVIS value of 0.285, which is below the cut-off value of 3 (UN GHS no category) and consequently it is not classified for irritation or serious eye damage according to UN GHS classification.
Executive summary:

The purpose of this study was to determine a possible potency of read-across test item IsoQure UR 300 of being ocular corrosive and severe irritant employing an in vitro system.The Bovine Corneal Opacity and Permeability Assay (BCOP) test method is an organotypic model that provides short-term maintenance of normal physiological and biochemical function of the bovine cornea in vitro. Three corneas were used for each treatment group (test item, solvent control and positive control). The solid test item was suspended in a 0.9% sodium chloride solution with a final concentration of 20% IsoQure UR 300as recommended in the test guideline 437 for non-surfactant solids.0.9% NaCl solution was used as the solvent control and 20% Imidazole in0.9% NaCl solution as the positive control item. The test item and the controls were applied to the epithelial surface of the cornea by addition to the anterior chamber of the corneal holder. The exposure time for the test item and the controls was 240 minutes. The optical density (OD) was measured at a wavelength of 490 nm. The acceptance criteria of validity were fulfilled in this test. Following treatment with IsoQure UR 300 a mean opacity of 0.305±0.354 and a mean permeability value of <0.001 compared to the negative control were determined. The calculated IVIS of 0.285±0.362 is below the cut-off value of 3 (UN GHS no category). Hence, the read-across test item did not show severely irritant or corrosive properties and consequently it is not classified for irritation or serious eye damage according to UN GHS classification. The same applies to Monuron.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No information was available for Monuron, however key read-across information was available from source substance Monuron (see attached read-across justification in Section 13).

Skin irritation

A key in vitro EpiDerm™ study was performed to determine cytotoxic properties of read-across substance Fenuron to skin cells, which might lead to irritation of human skin, by using an artificial three-dimensional model of human skin (Spruth, 2018a). Fenuron was applied as solid test item to the model skin surface, moistened with Dulbecco’s phosphate buffered saline (D-PBS).D-PBS was used as the negative control. 5% aqueous sodium dodecyl sulphate (SDS) was used as the positive reference item. An exposure time of 60 minutes was employed followed by a 42-hour post-treatment incubation period in fresh medium. The mean viability of cells exposed to Fenuron was 99.7% of the negative controls and, hence, was well above the cut-off percentage cell viability value that distinguishes irritant from non-irritant test items of > 50%. Fenuron and therefor also Monuron was considered to be non-cytotoxic and predicted to be non-irritant to skin.

Skin irritation

A key Bovine Corneal Opacity and Permeability Assay (BCOP) was performed to determine a possible potency of read-across substance Fenuron of being ocular corrosive and severe irritant employing an in vitro system. The solid test item was suspended in a 0.9% sodium chloride solution with a final concentration of 20% Fenuron as recommended in the test guideline 437 for non-surfactant solids.0.9% NaCl solution was used as the solvent control and 20% Imidazole in0.9% NaCl solution as the positive control item. The test item and the controls were applied to the epithelial surface of the cornea by addition to the anterior chamber of the corneal holder. The exposure time for the test item and the controls was 240 minutes. The optical density (OD) was measured at a wavelength of 490 nm. Following treatment with Fenuron the calculated IVIS was 0.285 ±0.362 is below the cut-off value of 3 (UN GHS no category). Fenuron and therefore also Monuron is considerd to be non-irritant and non-corrosive to eye.

Justification for classification or non-classification

Fenuron was non-cytotoxic in an artificial three-dimensional model of human skin, hence, the test item did not show irritant properties and is not classified as for skin corrosion/irritation according to CLP (No. 1272/2008 of 16 December 2008). The same applies to Monuron.

Fenuron resulted in an IVIS of 0.285 in the BCOP assay, which is below the cut-off value of 3, hence it is not classified for irritation or serious eye damage according to CLP (No. 1272/2008 of 16 December 2008). The same applies to Monuron.