Registration Dossier

Administrative data

Description of key information

In two primary skin irritation tests according or similar to OECD test guideline 404, bis(isopropyl)naphthalene (DIPN) was demonstrated to be not irritating on basis of EU regulations (Hazleton, 1982; IBR, 1986).
In two primary eye irritation tests according or similar to OECD test guideline 405, DIPN proved to be not irritating on basis of EU regulations (Hazleton, 1982; IBR, 1986).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: H. Fortkamp, Lengerich, Germany
- Age at study initiation: 11 - 17 weeks
- Weight at study initiation: 2.06 - 2.47 kg
- Housing: singly in steel cages with perforated plate floors above litter-filled dung troughs
- Diet (e.g. ad libitum): Ssniff K complete rabbit diet (Ssniff Versuchstier-Diäten GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -23
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
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 mL
Duration of treatment / exposure:
4 hour(s)
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk, size ca. 2.5 x 2.5 cm
- % coverage: no data
- Type of wrap if used: impermeable adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining test substance was removed by wiping with single-use paper towels.
- Time after start of exposure: 4 h

SCORING SYSTEM: according to Draize (similar to table "Grading of Skin Reactions" of OECD TG 404)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
1.5
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: see other effects
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: see other effects
Other effects:
In one animal, a slight lesion (48 h) and scab formation (72 h) was observed at the application site. All animals showed desquamation at day 7. After 14 days, irritation effects had subsided, and no more findings were noted.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a primary skin irritation test, diisopropylnaphthalene was found to be slightly irritating according to the scoring system of Draize. According to EU regulations, no classification as to skin irritation is required.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: scoring system
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: H. Fortkamp, Lengerich, Germany
- Age at study initiation: 11 - 17 weeks
- Weight at study initiation: 2.36 - 2.46 kg
- Housing: singly in steel cages with perforated plate floors above litter-filled dung troughs
- Diet (e.g. ad libitum): Ssniff K complete rabbit diet (Ssniff Versuchstier-Diäten GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -23
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye of the animals served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL; test substance was instilled into the conjunctival sac of the left eye. Then, the eye was held closed by gently pressing both eye lids together for about 1 - 2 seconds.
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): following application no further treatment of the eye

SCORING SYSTEM: according to Draize; grading scale (additional parameters included: discharge of conjunctiva and area of cornea involved) and scoring different from OECD TG 405

TOOL USED TO ASSESS SCORE: the eyes of test animals were examined after application of 2% fluorescein solution
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
0
Max. score:
110
Reversibility:
fully reversible within: 1 d
Remarks on result:
other: After one hour, slight redness (score 1) was observed in all three test animals.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effetcs
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Only a slight irritating effect (conjunctivae redness score 1) was observed in all test animals at 1 hour after test substance administration. At 24 hours, this finding had subsided and was not seen any more. Scores for all eye irritation parameters were 0 starting from 24 hours onwards. Observation ended at 72 hours.
Interpretation of results:
not irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

Two valid studies are available to assess the skin irritating potential of bis(isopropyl)naphthalene (DIPN). In both studies, DIPN was demonstrated to be not irritating according to EU regulations.

Hazleton 1982

In a primary skin irritation test according to OECD TG 404, DIPN was found to be slightly irritating according to the scoring system of Draize. With respect to EU regulations, no classification/labeling as to skin irritation is required.

IBR 1986

In a primary skin irritation test following OECD TG 404, DIPN caused slight erythema (score 1) on shaved rabbit skin still present in 4 of 6 animals after 72 hours, but no edema. Based on the scores observed, effects are expected to subside within 14 days. DIPN does not require classification/labeling according to EU regulations.

 

Eye irritation

Two valid studies are available to assess the eye irritating potential of DIPN. In both studies, DIPN was demonstrated to be not irritating according to EU regulations.

Hazleton 1982

In a primary eye irritation study according to OECD TG 405, only a slight irritating effect (conjunctivae redness score 1) was observed in all test animals at 1 hour after test substance administration. At 24 hours, this finding had subsided and was not seen any more. Scores for all eye irritation parameters were 0 starting from 24 hours onwards. Observation ended at 72 hours.

IBR 1986

In a primary eye irritation study following OECD TG 405, DIPN was shown to exhibit slight irritating effects on conjunctivae. According to EU regulations, scores were too low to require classification/labeling. At the end of the observation time (72 h), the effects noticed had not completely disappeared. Based on the scores observed and considering the time remaining for a 14 day period, effects are likely to subside completely.

Justification for classification or non-classification

Skin irritation/corrosion

Diisopropylnaphthalene showed slight irritation effects upon application to rabbit skin (see above). Irritation scores were below irritation criteria set in either directive 67/548/EEC or Regulation (EC) No 1272/2008. Effects observed were reversible within a 14 day period. Classification of diisopropylnaphthalene is not required.

 

Eye irritation

In only one of two valid eye irritation tests, slight irritation effects were observed on the conjunctiva of rabbit's eyes treated with diisopropylnaphthalene. Scores were below classification criteria of directive 67/548/EEC or Regulation (EC) No 1272/2008. Effects are considered reversible within 14/21 days. (observation time only 72 h). Classification of diisopropylnaphthalene is not required.