Registration Dossier

Administrative data

Description of key information

Skin irritation:
Mallory VT (1981) determined in a KL 2 study the skin irritation potential of NMMO in New Zealand White rabbits according to a method similar to OECD Guideline 404. NMMO was observed to be slightly irritating to the skin.

Based on theresults of this study and the criteria of the CLP Regulations, the substance does not have to be classified as skin irritant.

This study was selected as key study.


Eye irritation:
Mallory VT (1981) determined in a KL 1 study the eye irritation potential of NMMO in New Zealand White rabbits according to a method similar to OECD Guideline 405 and EU Method B.5. NMMO was observed to be slightly irritating to the eyes.

Based on the CLP criteria, the substance does not have to be classified as eye irritant.

This study was selected as key study.

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:
From November 17, 1981 through November 21, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Also abraded skin was exposed. Exposure for 24h. Occlusive dressing used.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglasville, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Housing: Separate isolation by the test system; rabbits were housed individually in cages sized in accordance with the "Guide for the Care of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging, and scattering
- Water (e.g. ad libitum): Availability - fresh tap water, fit for human consumption, ad libitum, using 16 ounce glass bottles with rubber stopper and stainless steel sipper tube or an automatic watering system supplied by Edstrom Industries Inc., Waterford, Wisconsin.
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site
Duration of treatment / exposure:
24 hours
Observation period:
Animals were observed for signs of erythema and edema and scored according to the Draize scale at 1, 24, 48 and 72 hours after application of the test material.
Number of animals:
Six (three males, three females)
Details on study design:
TEST SITE
- Area of exposure: The test article was administered at two skin sites, one abraded and one intact site.
- Type of wrap if used: Following nthe application of the test material, one-inch square gauze patches were applied to each of the two sites. The trunk of the animal was then wrapped with a rubber dam and an Ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 24 hour exposure period, the wrappings were removed and the skin wiped to remove any remaining material. Animals were observed for signs of erythema and edema and scored according to the Draize scale at 1, 24, 48 and 72 hour after the application of the test material.

SCORING SYSTEM: Draize evaluation of dermal irritation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Only intact skin taken into account
Irritation parameter:
edema score
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Only intact skin taken into account
Irritant / corrosive response data:
Slight erythema was visible only at one hour after bandage removal in 3 animals. No edema was observed throughout the study.
Other effects:
No effects on body weight.
Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the primary dermal irritation study in rabbits, the test article was not considered to be a dermal irritant. Based on the results of this test and the criteria of the CLP Regulation, the substance should not be classified for skin irritation.
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:
From November 17, 1981 through November 24, 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Inc., Douglassville, Pennsylvania
- Weight at study initiation: males 2.021-2.096 kg; females 2.103-2.124 kg
- Housing: Separate isolation by test system; rabbits were housed individually in cages sized in accordance with the "Guide for the Care of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce boiling, bridging, and scattering.
- Water (e.g. ad libitum): Availability - fresh tap water, fit for human consumption, ad libitum, using 16 ounce glass bottles with rubber stopper and stainless steel sipper tube or an automatic watering system supplied by Edstrom industries, Inc., Waterford, Wisconsin
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): 51-58%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral eye remained untreated and served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours and 7 days after treatment.
Number of animals or in vitro replicates:
six animals
Details on study design:
SCORING SYSTEM: An animal exhibited a positive reaction when the test substance produced one or more of the following signs: ulceration of the cornea (other than a fine stippling), opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels), and obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids and a diffuse crimson color with individual vessels not easily discernible.

Grading: according to the method of Draize

Classification of the test substance:
Non-irritant: 0 or 1 rabbit with positive scores
Indeterminate: 2 or 3 rabbtis with positive scores
Irritant: 4 to 6 rabbits with positive scores
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
based on 6 animals
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
based on 6 animals
Time point:
other: 24, 48, 72 hours
Score:
0.22
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Five rabbits exhibited a positive response at the one hour observation period. Two rabbits exhibited a positive response at the 24 hour reading. One positive response was observed at the 48 hour reading. No positive responses were observed at 72 hour or on day 7. Eight positive responses were recorded during the course of the study.
Other effects:
No effects on body weight.
Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the Acute Eye Irritation Test in Rabbits, the substance was determined to be a mild eye irritant. Based on the CLP classification criteria, the substance does not need to be classified for eye irritation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

Mallory VT (1981) studied skin irritation/corrosion by applying NMMO on one intact and one abraded site. At the end of the 24 hour exposure period, the wrappings were removed and the skin wiped to remove any remaining material. Animals were observed for signs of erythema and edema and according to the Draize scale at 1, 24, 48 and 72 hours after the application of the test material. Slight erythema was visible only at one hour after bandage removal in 3 animals. No edema was observed throughout the study. Based on the observations made in the primary dermal irritation study in rabbits, the test article was not considered to be a dermal irritant.

In a supporting KL 2 study very slight erythema was noted at one abraded site at the 24-hour reading. No other irritative or corrosive effects were noted at any time. The primary irritation index was found to be 0.04.

Based on the results of these tests and the criteria of the CLP Regulation, the substance should not be classified for skin irritation.

Eye irritation:

Mallory VT (1981) studied eye irritation by applying 0.1 mL NMMO to the eye of 6 New Zealand White rabbits. The other untreated eye served as control. The eyes were examined at 1, 24, 48 and 72 hours and 7 days after treatment. An animal exhibited a positive reaction when the test substance produced one or more of the following signs: ulceration of the cornea (other than a fine stippling), opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels), or and obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids and a diffuse crimson color with individual vessels not easily discernible. Five rabbits exhibited a positive response at the one hour observation period. Two rabbits exhibited a positive response at the 24 hour reading. One positive response was observed at the 48 hour reading. No positive responses were observed at 72 hour or on day 7. Eight positive responses were recorded during the course of the study. Based upon the observations in the Acute Eye Irritation Test in Rabbits, the authors determined the substance to be a mild eye irritant. However, based on the CLP classification criteria, the substance does not need to be classified for eye irritation.

In a supporting KL study application of the substance to the eyes of New Zealand White rabbits produced conjunctival erythema in four rabbits. As no information is available on effects later than 72h, reversibility of shown effects cannot be judged.

Justification for classification or non-classification

According to the criteria of the CLP Regulation, NMMO does not have to be classified as irritating to the skin nor to the eyes.