Registration Dossier

Administrative data

Description of key information

Skin irritation:
There were no signs of dermal irritation seen after 24, 48, and 72 hour exposures of NDC to rabbits (mean score = 0) (IIT Research Institute, 1990).
Eye irritation:
There were no signs of eye irritation after 24, 48, and 72 hour exposures of NDC to rabbits (mean cornea score = 0, mean iris score = 0, mean conjunctivae score 0.33 and mean chemosis score 0.11) (IIT Research Institute, 1990).

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:
November 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
NDC was applied for 4 hours to the pre-moistened, shaved backs of three rabbits at a dose of 0.5 g. Following unwrapping, the test sites were rinsed with approximately 2 mL of 0.9% saline. All test sites were examined for signs of dermal irritation (i.e., edema, erythema and/or eschar formation) and corrosivity (i.e., ulceration and/or necrosis) at 30-60 minutes, and 24, 48 and 72 hours following removal of the wrappings.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
None stated.



Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

No additional data
Duration of treatment / exposure:
4 hours
Observation period:
30-60 minutes, 24, 48 and 72 hours
Number of animals:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were rinsed with approximately 2 mL of 0.9% saline.
- Time after start of exposure: 4 hours

No additional data
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
No signs of dermal irritation were evident in any rabbit at any time during the study. The Primary Dermal Irritation Score for Dimethyl-2,6-Naphthalene Dicarboxylate (DM-2,6-NDC) is 0.0.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a dermal irritation study conducted equivalent to OECD 404 (not conducted according to GLP), no signs of irritation were seen 24, 48 and 72 hours after exposure of rabbits to NDC (mean score = 0), therefore, NDC is considered not irritating.
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:
November 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
NDC was placed in the right eye of each of three rabbits at a dose of 0.1 g, with the left eye serving as an untreated control. The treated eye of each rabbit was scored for irritation at 1, 24, 48, and 72 hours following test article application. The control eye was used for comparison.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-4 months of age
- Weight at study initiation: approximately 2.0-3.5 kg
- Housing: Each rabbit will be housed individually in a stainless steel cage (45.5 x 41 x 61 cm) suspended over excrement pans.
- Diet (e.g. ad libitum): Approximately 150 g of Purina Lab Rabbit Chow HF #5326 will be provided daily for each rabbit.
- Water (e.g. ad libitum): Water purified by reverse osmosis will be provided ad libitum by means of an automatic watering system.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature will be regulated to avoid extreme fluctuations.
- Humidity (%): Humidity will be regulated to avoid extreme fluctuations.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

No additional data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
at a dose of 0.1 g
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: DRAIZE

No additional data
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hrs
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hrs
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hrs
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean of 24, 48 & 72 hrs
Score:
0.11
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
The maximum eye irritation score of 6.7/110.0 was obtained 1 hour after application of Dimethyl-2,6-Naphthalene Dicarboxylate (DM-2,6-NDC).

Cornea (Density of Opacity)

Animal Number

Sex

Scoring Interval

1 hr

24 hr

48 hr

72 hr

Meana

626

627

628

M

F

F

0

0

0

0

0

0

0

0

0

0

0

0

0.0

0.0

0.0

Iris

Animal Number

Sex

Scoring Interval

1 hr

24 hr

48 hr

72 hr

Meana

626

627

628

M

F

F

0

0

0

0

0

0

0

0

0

0

0

0

0.0

0.0

0.0

Conjunctiva

Animal Number

Sex

Scoring Interval

1 hr

24 hr

48 hr

72 hr

Meana

Ab

Bc

A

B

A

B

A

B

A

B

626

627

628

M

F

F

1

1

2

1

0

2

0

0

2

0

0

1

0

0

1

0

0

0

0

0

0

0

0

0

0.0

0.0

1.0

0.0

0.0

0.3

aExcludes the 1-hr scores, as per the EEC criteria.

bA = Erythema

cB = Chemosis

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
NDC was found to be a non-irritant to the eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

This registration contains a combined approach for addressing the required endpoints. The required endpoints are addressed using, when available, data on the substance to be registered, dimethyl naphthalene-2,6-dicarboxylate (CAS Number 840-65-3) (NDC). When these data are not available, data from the following close structural analogs is used to address the required endpoints. 

 

·        naphthalene-2,6-dicarboxylic acid (CAS number 1141-38-4); and

 

Naphthalene-2,6-dicarboxylic acid is structurally similar to NDC, the registered substance, with a smiles code of c12c(cc(C(O)=O)cc2)ccc(c1)C(O)=O compared to that of c12c(cc(C(OC)=O)cc2)ccc(c1)C(OC)=O of NDC. The additional two methyl groups present in NDC are not expected to cause any significant differences in the toxicological effects of the registered substance nor it's degradation products.

 

Naphthalene-2,6-dicarboxylic acid data are used to address the following endpoints:

 

·        Skin irritation (supporting study); and

·        Eye irritation (supporting study).

Skin irritation

Key study:

In the key study conducted equivalent to OECD Guideline 404 (not conducted according to GLP), no signs of dermal irritation were seen after 72 hour exposure to rabbits (species not specified) with NDC (mean score = 0) (IIT Research Institute, 1990).

 

Supporting studies:

In a study, conducted equivalent to OECD Guideline 404 (not conducted according to GLP), no signs of dermal irritation were seen after 72 hour exposure to New Zealand White rabbits with NDC (mean score = 0.2) (Industrial BIO-TEST Laboratories, Inc., 1974).

 

In a read across study, conducted equivalent to OECD 404 (not conducted according to GLP), after 72 hour exposure to New Zealand White rabbits with naphthalene-2,6-dicarboxylic acid (EC Number 214-527-0 and CAS Number 1141-38-4), there were no signs of dermal irritation seen in any test animal during the study (mean score 0.2) (IIT RESEARCH INSTITUTE, 1991).

 

In a read across study, (no guideline followed, the test procedure was modeled after that of Draize et al., not conducted according to GLP), no signs of dermal irritation were seen after 72 hour exposure to New Zealand White rabbits with 2,6 -dimethylnaphthalene (EC number 209 -464 -0 and CAS number 581 -42 -0) (mean score = 0) (Industrial BIO-TEST Laboratories, Inc., 1974).

Eye irritation

Key study:

In the key study, conducted equivalent to OECD Guideline 405 (not conducted according to GLP), no signs of eye irritation were seen after 24, 48, and 72 hour exposure to New Zealand White rabbits with NDC (mean cornea score = 0, mean iris score = 0, mean conjunctivae score = 0.33 and mean chemosis score = 0.11) (IIT Research Institute, 1990).

 

Supporting studies:

In a study, conducted equivalent to OECD Guideline 405 (not conducted according to GLP), no signs of eye irritation were seen after 24, 48, and 72 hour exposure to New Zealand White rabbits with NDC, (mean cornea score = 0, mean iris score = 0, mean conjunctivae score = 0.33 and mean chemosis score = 0.11) (IIT Research Institute, 1990).

 

In a study, conducted equivalent to OECD Guideline 405 (not conducted according to GLP), no signs of eye irritation were seen after exposure to rabbits (species not specified) with NDC (IIT Research, Institute, 1990).

 

In a read across study, conducted equivalent to OECD Guideline 405 (not conducted according to GLP), 2,6 -dimethylnaphthalene (EC number 209 -464 -0 and CAS number 581 -42 -0) is considered not irritating to eyes after 24 and 48 hour exposure to New Zealand White rabbits (mean cornea score = 0.42, mean iris score = 0.17, mean conjunctivae score = 0.5 and mean chemosis score = 0.17, all fully reversible within 7 days) (Industrial BIO-TEST Laboratories, Inc., 1974).

 

In a read across study, conducted equivalent to OECD Guideline 405 (not conducted according to GLP), naphthalene-2,6-dicarboxylic acid (EC Number 214-527-0 and CAS Number 1141-38-4), is considered not irritating to eyes after 24 and 48 hour exposure to New Zealand White rabbits (mean cornea score = 0.11, mean iris score = 0, mean conjunctivae score = 0.78, and mean chemosis score = 0.78 all fully reversible within 72 hours) (IIT Research, Institute, 1990).


Justification for selection of skin irritation / corrosion endpoint:
This study was carried out with rabbit based on equivalent or similar to OECD 404. The study was not conducted according to GLP. This was considered not to effect validity.

Justification for selection of eye irritation endpoint:
This study was carried out with rabbit based on equivalent or similar to OECD 405. Study used FDA GLP conditions as an alternative, this was considered not to effect validity.

Justification for classification or non-classification

Skin irritation:

In the key study conducted equivalent to OECD 404 (not conducted according to GLP),there were no signs of dermal irritation after 24, 48, and 72 hour exposures of NDC to rabbits (mean score = 0) (IIT Research Institute, 1990), therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, NDC is not classified for skin irritation/corrosion.

 

Eye irritation

In the key study conducted equivalent to OECD 405 (not conducted according to GLP),There were no signs of eye irritation after 24, 48, and 72 hour exposures of NDC to rabbits (cornea score (mean) = 0, iris score (mean) = 0, conjunctival redness (mean) = 0.33 & chemosis (mean) = 0.11) (IIT Research Institute, 1990), therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, NDC is not classified for eye irritation.