Registration Dossier

Administrative data

Description of key information

Benzyl toluene was found to be irritant to skin and slightly irritating to eye.

 

Skin irritation:

For this endpoint, three valid in vivo studies are available. They show that benzyltoluene is irritating for skin, but this irritating potential is considered between low and moderate.

 

The key study (Mürmann, 1994) is an OECD 404 study that was performed according to GLP with a substance of very high purity. In this study, benzyl toluene was applied undiluted to the skin of 3 Small White Russian rabbits and held in contact for 4 hours by means of a semi-occlusive dressing. Mean scores over 24, 48 and 72 hours for each animal were for erythema and for edema. Animals were then observed daily until day 15. Average scores (24, 48 and 72 hours) for animals 1, 2 and 3 for erythema were 2.33, 3.0 and 3.0 and for edema were 3.0, 4.0 and 4.0, respectively. These clinical signs were fully reversible within 14 days.

In another study (Hüls, 1987), a mixture with benzyltoluene at 60 % was tested and found to be slightly irritating to skin, nevertheless, all the clinical signs were not fully reversible within 14 days.

In another study, the dermal irritation potential of benzyl toluene was determined in rabbits according to ETAD (Ecological and Toxicological of the Dyestuffs Manufacturing Industry) Method n°003 (1976) (Gobron, 1981). Twenty-four hours before treatment, the flank of six male New-Zealand rabbits were carefully shaved and the left sides were slightly scarified. Benzyl toluene was applied at the dose level of 0.5 g per animal and was held in contact with the scarified and the intact skin for 24 hours by a semi-occlusive dressing. Slight erythema (mean scores of 0.83 and 0.5 at 24 and 72h, respectively) and very slight to slight edema (mean scores of 1.0 and 0.5 at 24 and 72h, respectively) were observed after the removal of the dressing.

 

Eye irritation:

For this endpoint, three studies in rabbits are available.

 

In the key study (Mürmann, 1994), chosen for its accordance with OECD guideline and its GLP status. A single dose of 0.1 mL of undiluted benzyl toluene was instilled into the conjunctival sac of one eye. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. After 1, 24 and 48 hour all animals showed distinct hyperemia of some blood vessels and slight conjunctival swelling. Exudation was observed after 1 hour in one animal. For up to 72 hours the animals showed swelling and redness of the skin of the outer eyelids, later on one animal had, in addition to scaling, bloodstained areas in places on this region of skin. In the other two animals at this time there was only slight redness and swelling of the skin of the outer eyelid, and scaling. After 10 days all animals were free of signs of irritation. Mean scores calculated for each animal over 24, 48 and 72 hours were (0.6) (1) and (1) for chemosis, (0) (0) and (0) for redness of the conjunctiva, (0) (0) and (0) for iris lesions and (0) (0) and (0) for corneal opacity. Therefore the substance is considered only as slightly irritating to eye.

 

Similar conclusion was found in another study OECD 405, not GLP, but performed with a mixture of lower purity (Hüls, 1987), only slight effects on conjunctivia were observed, all mean scores were well under 2.

The ocular irritation that could be induced by benzyl toluene was evaluated in the rabbit according to the method no. 003 of the Ecological and Toxicological of the Dyestuffs Manufacturing Industry and the principles of good laboratory practice (Gobron, 1981). A single application of 0,1 ml of benzyl toluene in its original form was placed into the conjunctival sac of the eye of six male New-Zealand rabbits. The eye was not rinsed after instillation of the test substance. The ocular reactions were observed one hour, 24, 48 and 72 hours after the instillation. Mean score values (24+48+72 h) for ocular irritation were 1.2, 1.3, 0.1 and 0.7 for chemosis, enanthema, congestion and opacity, respectively.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-10-24 to 1994-11-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: adult animals, no further details mentioned
- Weight at study initiation: 1.9 - 2.2 kg
- Housing: conventional, single housing in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K4 complete feed for rabbits, ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk Haltern, Germany
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: an adjacent area of untreated skin
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 cm³
Duration of treatment / exposure:
4 hours
Observation period:
30-60 minutes, 24, 48, 72 hours, 6, 8, 10, 14, 17 and 21 days after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm³ of the dorsal area of the trunk
- % coverage: not mentioned
- Type of wrap if used: The application area was covered with a mull patch which was secured in place with a non-irritating plaster. The patch was held in contact with the skin by a suitable semi-occlusive dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 2.89
- Edema: 3.56
Other effects:
dry skin surface, brownish skin discoloration, indurated skin surface, areas of scale, which became fissured and later on detached; one animal showed new smooth skin in places

Table #: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

30 - 60 min

2/2/2

 4/4/4

24 h

 3/3/3

 3/4/4

48 h

 3/3/3

 3/4/4

72 h

 2/3/3

 2/4/4

Average 24h, 48h, 72h

 2.89

 3.56

Reversibility*)

 c.

 c.

Average time (unit) for reversion

 14 days

 14 days

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Benzyltoluene is irritating to skin.
Executive summary:

The acute dermal irritation of benzyltoluene was evaluated in rabbits according to OECD 404 guideline. Benzyltoluene was applied undiluted to the skin of 3 Small White Russian rabbits and held in contact for 4 hours by means of a semi-occlusive dressing. Mean scores over 24, 48 and 72 hours for each animal were for erythema and for oedema. Animals were then observed daily until day 15. Average scores (24, 48 and 72 hours) for animals 1, 2 and 3 for erythema were 2.33, 3.0 and 3.0 and for edema were 3.0, 4.0 and 4.0, respectively. These clinical signs were fully reversible within 14 days.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1987-04-8 until 1987-05-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test substance not adequately described (e.g. lacking CAS no., Batch no.), non GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small white Russian, Chbb-SPF
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 2.3 - 2.6 kg
- Housing: individual housing in stainless steel cages
- Diet (e.g. ad libitum): K4 Complete feed for rabbits ad libitum, Ssniff Spezialfutter GmbH, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1 °C
- Humidity (%): 60 ± 5 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1987-04-28 To: 1987-05-13
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 cm³
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm² of the dorsal and lateral parts of the trunk
- % coverage: not mentioned
- Type of wrap if used: A gauze patch (2,5 x 2,5 cm) on the application area was covered with a polyethylene film (6 x 6 cm), this was then immobilised with an elastic dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to the guideline
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 day
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
- Erythema: 2.00
- Edema: 2.56
Other effects:
Two animals showed dryness of application area. After 8 days in the application area of all animals scab was formed, later on the scab was fissured. At day 14 one animal showed an intact skin, in the second animal the scab detached.

Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

2/2/2

 3/4/4

24 h

 2/2/2

 3/3/3

48 h

 2/2/2

 2/3/2

72 h

 2/2/2

 2/3/2

Average 24h, 48h, 72h

 2.00

 2.56

Reversibility*)

 n.c

 n.c.

Average time (unit) for reversion

 14 days

 14 days

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The substance was irritating according to the scores, but the clinical signs were not fully reversible within 14 days.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 21 to 24 April 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods (ETAD norm) with few deviations but not restrictions (period of observation was reduced as clinical signs decreased with time)
Qualifier:
according to
Guideline:
other: ETAD (Ecological and Toxicological of the Dyestuffs Manufacturing Industry) Method n°003 - 1976
Deviations:
yes
Remarks:
Some parameters, like the age of animals at study initiation, were not reported. Only the 24- and 72-h examination were performed (the 48-h examination was lacking).
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: not reported
- Weight at study initiation: 2 - 2.5 kg
- Housing: individually in polystyrene cage (0.55 mm x 0.35 mm x 0.32 mm)
- Diet (e.g. ad libitum): commercial diet
- Water (e.g. ad libitum): ad libitum in 1500- or 2000-mL feeding bottle
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 50 +/- 20
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12


IN-LIFE DATES: From: 21 April To: 24 April 1981
Type of coverage:
occlusive
Preparation of test site:
other: shaved 24 h befeore treatment on right flank and also shaved and additionally slightly incised on the left flank
Vehicle:
other: none
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE: No
Duration of treatment / exposure:
24 hour(s)
Observation period:
24 and 72 hours
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm2 for the left flank, not reported for the right flank
- % coverage: not reported
- Type of wrap if used: A gauze square is maintained on the zone of application by an impermeable plastic band, an elastic tubular band and fragments of adhesive wraps


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not relevant

SCORING SYSTEM: Skin erythema and oedema were noted from 0 (no observation) to 4 (severe)
Irritation parameter:
erythema score
Basis:
animal: mean #1 to 6
Time point:
24 h
Score:
0.83
Max. score:
4
Reversibility:
other: not evaluated
Remarks on result:
other: Rignt flank
Irritation parameter:
erythema score
Basis:
animal: mean #1 to 6
Time point:
72 h
Score:
0.5
Max. score:
4
Reversibility:
other: not evaluated
Remarks on result:
other: Right flank
Irritation parameter:
edema score
Basis:
animal: mean #1 to 6
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
other: not evaluated
Remarks on result:
other: Right flank
Irritation parameter:
edema score
Basis:
animal: mean #1 to 6
Time point:
72 h
Score:
0.5
Max. score:
4
Reversibility:
other: not evaluated
Remarks on result:
other: Right flank
Irritant / corrosive response data:
See table 1 and 2
Other effects:
CLINICAL FINDINGS: No observed effects.

MORTALlTY: No deaths occured.

Observation on Day 7 was planned, in case it was considered necessary. As cutaneous reactions observed at 72 hours were considered to be low and not requiring further animal observation, that planned on Day 7 were not performed

Observed cutaneous reactions were decreased at 72-h observation time when compared to the 24-h observation time.

Table 1 Individual skin irritation scores – Left flank (shaved and incised)

Erythema

Oedema

Animal sex

Males

Males

Animal No

1

2

3

4

5

6

1

2

3

4

5

6

After 24 h

1

1

1

1

1

1

0

0

2

1

2

1

After 72 h

1

1

0

1

0

1

0

1

1

0

1

1

Table 2 Individual skin irritation scores – Right flank (shaved but not incised)

Erythema

Oedema

Animal sex

Males

Males

Animal No

1

2

3

4

5

6

1

2

3

4

5

6

After 24 h

0

1

1

1

1

1

0

0

2

1

2

1

After 72 h

0

1

0

1

0

1

0

1

1

0

1

0

Interpretation of results:
GHS criteria not met
Conclusions:
The substance was found to be slightly irritating to rabbits skin with some slight oedema and erythema observed (maximum score 2). Observed cutaneous reactions were decresaed at 72-h observation time when compared to the 24-h observation time.
Executive summary:

The dermal irritation potential of benzyl toluenes was determined in rabbits according to ETAD (Ecological and Toxicological of the Dyestuffs Manufacturing Industry) Method n°003 (1976). Twenty-four hours before treatment, the flank of six male New-Zealand rabbits were carefully shaved and the left sides were slightly scarified. Benzyltoluene was applied at the dose level of 0.5 g per animal and was held in contact with the scarified and the intact skin for 24 hours by a semi-occlusive dressing. Slight erythema (mean scores of 0.83 and 0.5 at 24 and 72h, respectively) and very slight to slight oedema (mean scores of 1.0 and 0.5 at 24 and 72h, respectively) were observed after the removal of the dressing.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1994-11-07 to 1994-11-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: adult, no furhter details mentioned
- Weight at study initiation: 2.3 - 2.9 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): K4 complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GembH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasse, Wasserwerk, Halten, Germany
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1994-11-07 To: 1994-11-18
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 cm³
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48 and 72 hours, and 6, 8, 10 days after application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm phyiological saline
- Time after start of exposure: 24 hours


SCORING SYSTEM: acording to guideline


TOOL USED TO ASSESS SCORE: ophtmalic lamp, fluorescein at the end of exposure
Irritation parameter:
cornea opacity score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal: #2 and 3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0
- Iris: 0
- Conjuntivae (Redness): 0
- Conjuntivae (Chemosis): 0.89
Other effects:
After 1, 24 and 48 hour all animals showed distinct hyperamia of some blood vessels and slight conjuctival swelling. Exudation was observed after 1 hour in one animal. For up to 72 hours the animals showed swelling and redness of the skin of the outer eyelids, later on one animal had, in addition to scaling, bloodstained areas in places on this region of skin. In the other two animals at this time there was only slight redness and swelling of the skin of the outer eyelid, and scaling. After 10 days all animals were free of signs of irritation.

Table #: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

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

 1/1/1

 1/1/1

24 h

 0/0/0

 0/0/0

 0/0/0

 1/1/1

48 h

 0/0/0

 0/0/0

 0/0/0

 1/1/1

72 h

 0/0/0

 0/0/0

 0/0/0

 0/1/1

Average 24h, 48h, 72h

 0

 0

 0

 0.89

Area effected

 -

-

 -

 -

Maximum average score (including area affected, max 110)

 0

 0

 0

Reversibility*)

 -

 c.

 c.

Average time (unit) for reversion

-

-

6 days

6 days

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was slightly irritant when administered by ocular route to rabbits.
Executive summary:

The potential of benzyltoluene to induce ocular irritation was evaluated in rabbits according to OECD No. 405. Benzyltoluene was first administered to three male New Zealand White rabbit. A single dose of 0.1 mL of undiluted benzyltoluene was instilled into the conjunctival sac of one eye. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. After 1, 24 and 48 hour all animals showed distinct hyperamia of some blood vessels and slight conjuctival swelling. Exudation was observed after 1 hour in one animal. For up to 72 hours the animals showed swelling and redness of the skin of the outer eyelids, later on one animal had, in addition to scaling, bloodstained areas in places on this region of skin. In the other two animals at this time there was only slight redness and swelling of the skin of the outer eyelid, and scaling. After 10 days all animals were free of signs of irritation. Mean scores calculated for each animal over 24, 48 and 72 hours were (0.6) (1) and (1) for chemosis, (0) (0) and (0) for redness of the conjunctiva, (0) (0) and (0) for iris lesions and (0) (0) and (0) for corneal opacity. Under these experimental conditions, the test item was slightly irritant when administered by ocular route to rabbits.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 21 to 24 April 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods (ETAD norm) with few deviations but no restrictions
Qualifier:
according to
Guideline:
other: ETAD (Ecological and Toxicological of the Dyestuffs Manufacturing Industry) Method n°003 - 1976
Deviations:
yes
Remarks:
The age of animals at study initiation was not reported. Eye reactions were not observed after 72 hours.
GLP compliance:
yes
Species:
rabbit
Strain:
other: New-Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: not reported
- Weight at study initiation: 2 - 2.5 kg
- Housing: individually in polystyrene cage (0.55 mm x 0.35 mm x 0.32 mm)
- Diet (e.g. ad libitum): commercial diet
- Water (e.g. ad libitum): ad libitum in 1500- or 2000-mL feeding bottle
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 50 +/- 20
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12


IN-LIFE DATES: From: 21 April To: 24 April 1981
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
The eyes were not rinsed after administration of the test substance
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no


SCORING SYSTEM: treated eyes were scored for conjunctival lesions and discharge, iris lesions and corneal lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Maximum score was observed 1 day following eye instillation of test substance. Although not fully reversible, individual scores had the tendency to be decreased by day 3 (maximum score: 1)
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within:
Remarks on result:
other: Maximum score was observed 1 hour following eye instillation of test substance. Although not fully reversible, individual scores had the tendency to be decreased by day 3 (maximum score: 1)
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: Maximum score was observed 1 day following eye instillation of test substance. Although not fully reversible, individual scores had the tendency to be decreased by day 3 (maximum score: 1)
Irritant / corrosive response data:
The substance was showed to be slightly irritating.
Other effects:
No other clinical signs were observed.

Observation on Day 7 was planned, in case it was considered necessary. As observation on Day 7 was not performed, eye reactions observed at 72 hours were considered to be low and not requiring further animal observation.

Table 1 Individual eye irritation scores

Corneal opacity

Iris

Animal No

01

02

03

04

05

06

01

02

03

04

05

06

After 1 h

0

0

0

0

0

0

0

0

0

0

0

0

After 24 h

1

1

1

1

2

1

0

1

1

0

0

0

After 48 h

0

0

1

0

1

1

0

0

0

0

0

0

After 72 h

0

0

0

0

1

1

0

0

0

0

0

0

Mean scores 24-72 h

0.67

0.11

Conjunctivae

Redness

Chemosis

Animal No

01

02

03

04

05

06

01

02

03

04

05

06

After 1 h

2

2

2

3

2

2

2

2

1

0

1

2

After 24 h

2

1

2

2

2

2

3

2

3

2

3

3

After 48 h

2

1

1

2

2

2

2

0

1

0

2

1

After 72 h

1

0

0

1

1

0

1

0

1

0

0

0

Mean scores 24-72 h

1.33

1.33

Interpretation of results:
GHS criteria not met
Executive summary:

The ocular irritation that could be induced by benzyl toluenes was evaluated in the rabbit according to the method no. 003 of the Ecological and Toxicological of the Dyestuffs Manufacturing Industry and the principles of good laboratory practice. A single application of 0,1 ml of benzyl toluene in its original form was placed into the conjonctival sac of the eye of six male New-Zealand rabbits. The eye was not rinsed after instillation of the test substance. The ocular reactions were observed one hour, 24, 48 and 72 hours after the instillation. Mean score values (24+48+72 h) for ocular irritation were 1.2, 1.3, 0.1 and 0.7 for chemosis, enanthema, congestion and opacity, respectively.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1987-05-05 to 1987-05-12
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small White Russian, Chbb-SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 2.0 - 2.3 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): K4 complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1987-05-05 To: 1987-05-12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 cm³
- Concentration (if solution): undiluted
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 24, 48 and 72 hours, 6 and 7 days after application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm phyiological saline
- Time after start of exposure: 72 hours


SCORING SYSTEM: according to guideline


TOOL USED TO ASSESS SCORE: ophtmalic lamp, fluorescein 72 hours after administration
Irritation parameter:
cornea opacity score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
animal: all
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and 3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0
- Iris: 0
- Conjuntivae (Redness): 0.44
- Conjuntivae (Chemosis): 0
Other effects:
none

Table #1: Irritant/corrosive response data for each animal at each observation time of each animal from the test

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

 1/2/2

 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

 0/1/0

 0/0/0

72 h

 0/0/0

 0/0/0

 0/0/0

 0/0/0

Average 24h, 48h, 72h

 0

 0

 0.44

 0

Area effected

 

 

 

 

Maximum average score (including area affected, max 110)

 

 

 

 

Reversibility*)

 

 

c. 

 

Average time (unit) for reversion

 

 

 72 hours

 

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

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

Additional information

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), benzyltoluene is classified as skin irritating, category 2.

Even the substance is slightly irritating to moderately irritating to eye, it should not be classified as irritating to eyes according to the criteria for classification laid down in EU Regulation (EC) N0. 1272/2008 (CLP).


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