Benzyltoluene

Endpoint summary

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

Reference

Reference 1

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Small White Russian

Details on test animals or test system 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.

Reference 2

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: Small white Russian, Chbb-SPF

Details on test animals or test system 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.

Reference 3

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

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 or test system 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

Reference

Reference 1

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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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	2
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.

Reference 2

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

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.

Reference 3

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

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)

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).