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Administrative data

Description of key information

Paradimethoxybenzene is slightly irritating to the eyes and not irritating to the skin in tests on rabbits, following OECD guidelines.

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 27 feb 2007 to 29 may 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Harlan Netherlands BV
Kreuzelweg 53
NL-5961 NM Horst / The Netherlands
Postbus 6174
NL-5960 AD Horst / The Netherlands
- Age at study initiation: 11 weeks (male); 11, 12 weeks (females)
- Weight at study initiation: between 2.3 to 3 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12. Music was played during the daytime light period.

IN-LIFE DATES: From 27 feb 2007 to 02 mar 2007
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: purified water
Controls:
other: the other flank served as control
Amount / concentration applied:
Concentration: 0.5 g
Concentration: moistened with purified water (0.5 ml)
pH: 6.84

- VEHICLE: purified water to moisten Paradimethoxybenzene
Duration of treatment / exposure:
4 hour(s)
Observation period:
72 hours
Number of animals:
3: 1 male and 2 females
Details on study design:
TEST SITE:
- Area of exposure: on left flank
- % coverage: 6.25 cm²
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE:
- Washing: flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according the Commission Directive 2004/73/EC april 29, 2004; and Directive 2001/59/EC, august 2001
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects

Table of results:

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

0/0/0

0/0/0 

24 h

0/0/0 

0/0/0

48 h

0/0/0 

0/0/0

72 h

0/0/0 

0/0/0

Average 24h, 48h, 72h

 0

Reversibility*)

No effects 

No effects  

 

Remark: The animals were not sacrificed. On completion of the observation period they were re-allocated to the eye irritation study (RCC Study B16086).

Interpretation of results:
GHS criteria not met
Conclusions:
Based on this test, the substance is not irritating
Executive summary:

In a primary dermal irritation study (RCC study number B16075), New Zealand White rabbits (1 male and 2 females) were dermally exposed to 0.5 g of Paradimethoxybenzene moistened with purified water for 4 hours to 6.25 cm² on left flank.

Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 72 hours.

Irritation was scored according to the EU classification criteria.

The scores were 0 for edema and 0 for erythema.

In this study, Paradimethoxybenzene is not a dermal irritant according to the EU classification criteria.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 02 mar 2007 to 29 may 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Source: Harlan Netherlands BV
Kreuzelweg 53
NL-5961 NM Horst / The Netherlands
Postbus 6174
NL-5960 AD Horst / The Netherlands
- Age at study initiation: 15 weeks (male); 13, 14 weeks (females)
- Weight at study initiation: between 2.6 to 3.2 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12. Music was played during the daytime light period.

IN-LIFE DATES: From 07 or 08 mar 2007 to 12 mar 2007
Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye served as control
Amount / concentration applied:
- TEST MATERIAL:
Amount applied: 0.1 g
Concentration: pure
pH: 6.84
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3: 1 male and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: according the Commission Directive 2004/73/EC april 29, 2004
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Other effects:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours  after instillation) for each animal for corneal opacity, iris, redness and 
chemosis of the conjunctivae, separately. The individual mean scores  for corneal opacity and iris were 0.00 for all three animals. The  individual 
mean scores for the conjunctivae were 0.33, 0.33 and 0.67 for  reddening, respectively and 0.00 for chemosis for the three animals. No abnormal 
findings were observed in the cornea or iris of any animal at  any of the measurement intervals. A slight to moderate reddening of the conjunctivae 
was noted in all  animals at the 1-hour observation and persisted as slight up to the  24-hour reading in two animals and up to the 48 -hour 
observation in one  animal. Additionally, all animals expressed a slight reddening of the  sclera 1 hour after instillation, which persisted in one female 24 hours later. Slight to moderate discharge was recorded in all three animals at  the 1 -hour reading.

Result table:

 

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

1/1/2

0/0/0

24 h

0/0/0

0/0/0

 1/1/1

0/0/0

48 h

0/0/0

0/0/0

 0/0/1

0/0/0

72 h

0/0/0

0/0/0

 0/0/0

0/0/0

Average 24h, 48h, 72h

0

0

 0.33/0.33/0.67

0

Reversibility*)

 No effects

No effects 

fully 

 No effects

 

Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating
Executive summary:

In a primary eye irritation study (RCC study number B16086), 0.1 g of Paradimethoxybenzene was instilled into the conjunctival sac of left eye of New Zealand White rabbits (1 male and 2 females). Animals then were observed for 72 hours.

Irritation was scored according to the EU classification criteria.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.33, 0.33 and 0.67 for reddening, respectively and 0.00 for chemosis for the three animals.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals In this study, Paradimethoxybenzene is not an eye irritant based on the EU classification criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 29 nov 1988 to 02 dec 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, conventional breeding
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.5 - 3 kg
- Housing: individually in cages, fully air-conditioned
- Diet: Altromin 2123 rabbit diet (Altromin GmbH) ad libitum, and hay ad libitum (approx. 15 g/day).
- Water: desionised water ad libitum
- Acclimation period: no data.
24 h before testing the eyes of the animals were treated with some drops of Florescein-Sodium-solution (0.01 &%) and checked for damages under UV-light. Only animals with eyes showing no damages were used.



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): Air-conditioned room
- Photoperiod (hrs dark / hrs light): 12h / 12h daily

Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye served as control
Amount / concentration applied:
100 mg of test substance into conjunctival sack of the left eye, one single application.
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours.
Points at 1, 24, 48 and 72 hours.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): saline solution
- Time after start of exposure: 24 hours
- check after 24 and 72 h:
after instillation of one drop of Flurorescein-sodium-solution (0.01 %) the cornea was checked under UV-light

SCORING SYSTEM: according to the OECD 405 guideline

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
other: No effect
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
other: No effect
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
other: No effect
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effect

Result table:

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

2/2/2 

2/2/1

24 h

1/0/0

0/0/0

1/1/0

0/0/0

48 h

0/0/0

0/0/0

1/0/0

0/0/0

72 h

0/0/0

0/0/0

 0/0/0

0/0/0

Average 24h, 48h, 72h

0.33/0/0

0

 0.66/0.33/0

0

Reversibility*)

 fully

No effects 

fully 

 No effects

 

Interpretation of results:
GHS criteria not met
Conclusions:
Paradimethoxybenzene is not irritating to the eyes.
Executive summary:

In a primary eye irritation study (Hoechst, 1988), 0.1 g of Paradimethoxybenzene was instilled into the conjunctival sac of left eye of New Zealand White rabbits (3 animals). Animals then were observed for 72 hours.

Irritation was scored according to the EU classification criteria.

The mean score was calculated across 3 scoring times, 24, 48 and 72 hours after instillation for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

The mean scores at 24, 48 and 72 hours for iris and Chemosis were 0. The mean scores at 24, 48 and 72 hours for the conjunctivae were 0.33, and for corneal opacity, 0.11.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

In this study, Paradimethoxybenzene is not an eye irritant based on the EU classification criteria.

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

Additional information

Skin:

Four studies were available and two studies with reliability 1 were selected, one as key study and the second one as supporting study.

In the first primary dermal irritation study (RCC study number B16075) (key study), New Zealand White rabbits (1 male and 2 females) were dermally exposed to 0.5 g of Paradimethoxybenzene moistened with purified water for 4 hours to 6.25 cm² on left flank. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 72 hours. Irritation was scored according to the EU classification criteria.
The scores were 0 for edema and 0 for erythema.

In the second one (Clariant, 1988) (supporting study), animals were tested with the same manner.

The mean scores at 24, 48 and 72 hours were 0 for edema and 0,2 for erythema.

In these studies, Paradimethoxybenzene is not a dermal irritant according to the EU classification criteria.

Eye:

Two studies with validity 1 were selected as key studies.

In the first primary eye irritation study (RCC study number B16086),0.1 g of Paradimethoxybenzene was instilled into the conjunctival sac of left eye of New Zealand White rabbits (1 male and 2 females). Animals then were observed for 72 hours. Irritation was scored according to the EU classification criteria.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for chemosis, corneal opacity and iris were
0.00for all three animals.

The individual mean scores for the conjunctivae were 0.33, 0.33 and 0.67, respectively.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

In the second primary eye irritation study (Hoechst, 1988), 0.1 g of Paradimethoxybenzene was instilled into the conjunctival sac of left eye of New Zealand White rabbits (3 animals). Animals then were observed for 72 hours.

Irritation was scored according to the EU classification criteria.

The mean score was calculated across 3 scoring times, 24, 48 and 72 hours after instillation for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

The mean scores at 24, 48 and 72 hours for iris and chemosis were 0 for all three animals.

 

The individual mean scores at 24, 48 and 72 hours for the conjunctivae were 0.66, 0.33 and 0, and 0.33, 0 and 0 for corneal opacity.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

In these studies, Paradimethoxybenzene is not an eye irritant based on the EU classification criteria.


Justification for classification or non-classification

Based on the two reliable studies, the substance is not classified irritant for the skin according to EU and UN GHS criteria.

Based on the two reliable studies, the substance is not classified irritant for the eyes according to EU and UN GHS criteria.