Registration Dossier

Administrative data

Description of key information

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: Guideline study (GLP; QAU)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: White Vienna animals from Gaukler; D-6050 Offenbach/Main, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: mean bw of 2.71 kg for males (2) and 2.51 kg for female (1)
- Housing: one animal per cage in cages made of stainless steel with wire mesh walk floors (floor area : 40 cm x 51 cm)
- Diet (e.g. ad libitum): Kliba 341, 4 MM; from Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water (e.g. ad libitum): about 250 ml tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a temperature range and a relative humidity. There were no deviations from these ranges which influenced the results of the study.
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin site of the same animals
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 hours (all irritation effects were reversible within 48 hours)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: upper third of the back or flanks; the fur was clipped at least 15 hours before the beginning of the study
- % coverage: . application site of 2.5 x 2.5 cm was covered with the 0.5 ml (526 mg) test substance
- Type of wrap if used: semiocclusive patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lutrol and lutrol/water 1:1
- Time after start of exposure: at the end of exposure period (4 hours)

SCORING SYSTEM: OECD scoring system
Readings: 30 - 60 min, and 24, 48, or 72 hours after removal of test patches
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all tested animals (3)
Time point:
other: 24-48-72-hour
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all tested animals (3)
Time point:
other: 24-48-72-hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no edema observed at any time point
Irritant / corrosive response data:
After 4 and 24 hours very slight (grade 1) erythema were obeserved for 2/3 animals. They were completely reversible within after 48 hours (see Table 1).
Other effects:
None observed

Table 1: Results acute skin irritation/corrosivity (OECD scores)

Test animal

After 30-60 min

After 24 hours

Âfter 48 hours

After 72 hours

Mean 24-48-72-hour

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

1

1

0

1

0

0

0

0

0

0.3

0.0

2

1

0

1

0

0

0

0

0

0.3

0.0

3

0

0

0

0

0

0

0

0

0

0.0

Mean

0.67

0

0.67

0

0

0

0

0

0.2

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU GHS
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: Guideline study (GLP, QAU)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: White Vienna animals from Gaukler; D-6050 Offenbach/Main, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: mean bw of 3.26 kg for males (2) and 3.69 kg for female (1)
- Housing: one animal per cage in cages made of stainless steel with wire mesh walk floors (floor area : 40 cm x 51 cm)
- Diet (e.g. ad libitum): Kliba 341, 4 MM; from Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water (e.g. ad libitum): about 250 ml tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a temperature range and a relative humidity. There were no deviations from these ranges which influenced the results of the study.
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Single application of test substance into the conjunctival sac of the right eye.
Duration of treatment / exposure:
72 hour(s)
Observation period (in vivo):
up to 3 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: OECD scoring system
Readings after 1, 24, 48 and 72 hours.
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Remarks:
of all animals tested
Time point:
other: 24-48-72-hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of all tested animals
Time point:
other: 24-48-72-hour
Score:
1.1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all tested animals
Time point:
other: 24-48-72-hour
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all tested animals
Time point:
other: 24-48-72-hour
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritant / corrosive response data:
All irritation reactions (only conjunctivae redness) were minimal (see Table 1) and reversible within 72 hours.
Other effects:
None observed

Table 1: Results acute eye irritation (OECD scoring system) 

period

Animal

Corneal opacity

Iris

Conjunctivae

Redness

Swelling (chemosis)

1 Hour after treatment

1

0

0

2

0

2

0

0

2

0

3

0

0

2

0

Mean 1 hour (3 animals)

 

0.0

0.0

2

0.0

24 Hour after treatment

1

0

0

2

0

2

0

0

2

0

3

0

0

2

0

Mean 24 hour (3 animals)

 

0.0

0.0

2

0.0

48 Hour after treatment

1

0

0

2

0

2

0

0

1

0

3

0

0

1

0

Mean 48 hour (3 animals)

 

0.0

0.0

1.3

0.0

72 Hour after treatment

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

Mean 72 hour (3 animals)

 

0.0

0.0

0.0

0.0

Mean 24-48-72-Hour

1

0.0

0.0

1.3

0.0

2

0.0

0.0

1.0

0.0

3

0.0

0.0

1.0

0.0

Mean 1 hour (3 animals)

 

0.0

0.0

1.1

0.0

 

 

 

 

 

 

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU GHS
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

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

Additional information

taken from EU RAR Dibutyl Phthalate (2004):

Conclusion on irritation

Dibutyl phthalate did not show skin or eye irritating properties in rabbits. According to EC criteria dibutyl phthalate does not need to be classified on the basis of the available tests.

According to BIBRA (1987) and BUA (1987), irritation of nasal mucous membranes was seen in mice after exposure by inhalation after 2 h at 0.25 mg/L. Gamer et al., (2000) showed that repeated exposure of rats to 509 mg DBP/m3 (~0.5 mg DBP/L) as aerosol caused red crust formation of snouts. At concentrations ≥1.18 mg/m3 (≥~0.001 mg/L) local (histopathological) effects in nasal cavity and larynx were seen, but no signs of inflammation (taken from EU RAR Dibutyl Phthalate (2004).

Based on these data DBP does not need to be classified for respiratory irritation

Justification for classification or non-classification

According to the EC criteria, dibutyl phthalate does not need to be classified on the basis of its irritation effects.