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Description of key information

In vitro studies of skin and eye irritation are available for [D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts].

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:
02/12/2016-03/17/2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
July 2015
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
D-glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
foreskin from a single donor
Source strain:
other: not relevant
Justification for test system used:
MatTeK EpiDerm(TM) is a validated RhE model specified by the OECD Guideline
Vehicle:
unchanged (no vehicle)
Details on test system:
EpiDerm(TM) Tissue Models (MAtTek)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
yes, concurrent MTT non-specific colour control
Amount/concentration applied:
30 microlitres
Duration of treatment / exposure:
60 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
All exposures were performed in triplicate
Irritation / corrosion parameter:
% tissue viability
Value:
78.2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
100.0%
Positive controls validity:
valid
Remarks:
3.4%
Remarks on result:
no indication of irritation
Remarks:
78.2% viability
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: no
- Colour interference with MTT: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

The average viability for the test material was 78.2%, showing a lack of skin irritation potential. Appropriate viability results for the negative control (100.0%) and positive control (3.4%) confirmed the sensitivity of the assay to detect skin irritants.

Interpretation of results:
GHS criteria not met
Conclusions:
D-glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts
Executive summary:

The skin irritation potential of the substance [D-glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts] was assessed in vitro in a study performed to GLP and OECD 439. 30 µL of the undiluted test material was applied to triplicate tissues (MatTex EpiDerm(TM) for 1 hour, prior to a 42 -hour post-exposure incubation period. Tissue viability was assessed by MTT reduction and measured photometrically. The mean viability of the treated tissue samples was 78.2%. Appropriate viability results for the negative control (100.0%) and positive control (3.4%) confirmed the sensitivity of the assay to detect skin irritants. D-glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts was found to be non-irritant under the conditions of this study, and does not require classification for skin irritation according to the CLP Regulation.

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:
experimental study
Adequacy of study:
key study
Study period:
October 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Isolated bovine cornea obtained from freshly slaughtered animals, age 12-48 months. Whole eyes were transported to the test facility in HBSS on ice. The eyes were carefully examined for pre-existing defects and used within 12 hours of collection.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
0.75 mL, undiluted
Duration of treatment / exposure:
10 minutes
Duration of post- treatment incubation (in vitro):
2 hours
Number of animals or in vitro replicates:
5 (negative control), 3 (test material) or 4 (positive control) replicates
Details on study design:
SELECTION AND PREPARATION OF CORNEAS

Isolated bovine cornea obtained from freshly slaughtered animals, age 12-48 months. Whole eyes were transported to the test facility in HBSS on ice.

QUALITY CHECK OF THE ISOLATED CORNEAS

The eyes were carefully examined for pre-existing defects and used within 12 hours of collection.

NUMBER OF REPLICATES

5 (negative control), 3 (test material) or 4 (positve control) replicates

NEGATIVE CONTROL USED

Water for irrigation

POSITIVE CONTROL USED

Ethanol

APPLICATION DOSE AND EXPOSURE TIME

0.75 mL; 10 minutes

TREATMENT METHOD

Closed chamber

REMOVAL OF TEST SUBSTANCE

- Number of washing steps after exposure period: 3

- POST-EXPOSURE INCUBATION

2 hours

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: illuminance
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)
- Other: visual observation

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: decision criteria as indicated in the TG was used.
Irritation parameter:
cornea opacity score
Run / experiment:
Mean IVIS from three replicates
Value:
2.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
Mean IVIS 38.45
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: none

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
Other effects:
None observed

 Test material Mean IVIS 2.3
 Positive control Mean IVIS 38.45 
Interpretation of results:
GHS criteria not met
Conclusions:
Based on a mean IVIS score of 2.3, the test material [D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts] does not require classification for serious eye damage or eye irritation according to the CLP Regulation.
Executive summary:

The potential of the test material [D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts] to cause serious eye damage was assessed in a BCOP assay (closed chamber method) performed to OECD 437. 0.75 mL of the test material was applied to the cornea (three replicates) for 10 minutes, followed by a 2-hour post-exposure incubation period. Corneal opacity was measured; corneal permeability was assessed using sodium fluorescein solution and measurement of absorption at 490 nm and IVIS scores calculated. Isolated corneas were also exposed in parallel to negative control (water) and positive control (ethanol) substances. A mean IVIS score of 2.3 was calculated for the test material, indicating that it does not require classification for serious eye damage or eye irritation according to the CLP Regulation. Responses to the negative and positive controls confirmed the integrity and sensitivity of the assay.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Based on the absence of skin and eye irritation, [D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts] is not predicted to be a respiratory irritant.

Justification for classification or non-classification

In vitro studies of skin irritation and eye irritation are available for [D-Glucose, reaction products with nitric acid and sodium nitrite (1:1), sodium salts].

Based on a mean tissue viability of 78.2% in an RhE skin irritation assay, the substance does not require classification for skin irritation according to the CLP Regulation.

Based on the mean IVIS score of 2.3 in a BCOP assay, the substance does not require classification for serious eye damage or eye irritation according to the CLP Regulation.