Registration Dossier

Administrative data

Description of key information

-Skin irritation: not irritating (published data, V2, 1982)
- Eye irritation: irritating (published data, V2, 1982)
- Respiratory irritation: no data available

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published data, it failed details on experimetal conditions
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: no detail on the animal and environmental conditions, use of an occlusive dressing. No information on individual irritation scores, therefore, skin reactions were not assessed with OECD Recommended Scoring System.
Principles of method if other than guideline:
Standard Draize method. The irritancy of the test item was then defined on the basis of the the primary dermal irritation index (PDII) using the scale appropriate for AFNOR protocol.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Roucher SA, Couhé.
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg.
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): not applicable, the test substance is applied undiluted

VEHICLE: not applicable, the test substance is applied undiluted

Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
six animals (Males)
Details on study design:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: approx. 6 cm2
- Type of wrap if used: occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Each treated area was scored for erythema and oedema according to the method of Draize (describe in: Draize, J. H., Woodard, G.& Calvery, H. O. (1948). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Pharmacol. 93, 377.)
Criteria used for interpretation based on Primary Dermal Irritation Index (PDII) according to AFNOR scale:
PDII below 0.5.................non irritant
0.5-3................................slightly irritant
3-5...................................moderately irritant
5-8...................................severely irritant
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0.21
Max. score:
8
Reversibility:
fully reversible within: 3 days
Irritant / corrosive response data:
As primary dermal irritation index (PDII) is 0.21. PDII is below 0.5 according to AFNOR scale, therefore, o-Diethoxybenzene is considered as not irritating to skin (see Table 7.3.1/1).
Other effects:
No data

Table 7.3.1/1: summary table of irritation scores results and PDII

Score at time point/reversibility

Erythema + Oedema (six animals)

Conclusion (Draize method)

60 min

4

Not irritating

 

(PDII below 0.5 )

24 h

4

48 h

2

72 h

0

PDII = 10/48 = 0.21 (Max: 8)

 

7 days

/

14 days

/

Reversibility

Yes, within 3 days

 

PDII*: the sum ((erythema + oedema) in all six animals at the reading times)/the total number of readings

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: AFNOR (1982)
Conclusions:
Under the test conditions, o-Diethyoxybenzene is not considered to be a skin irritant.
Executive summary:

In a non-GLP primary dermal irritation study (Guillot and al, 1982) performed similarly to the OECD No. 404, six male New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted o-Diethyoxybenzene to the dorsal surface of the trunk (skin was clipped before application) for 4 hours under an occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hour after patch removal using the Draize scale. The irritancy of the test item was then defined on the basis of the the primary dermal irritation index (PDII) using the scale appropriate for AFNOR.

PDII is 0.21, the test substance was therefore considered as non-irritant to the skin.

Under the conditions of this test, no classification for skin irritation is required according to the criteria of the CLP Regulation (EC) N°1272/2008 and the Directive 67/548/EEC.

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
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published data, it failed details on experimental conditions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Tests performed according to 3 methods: Cosmetics and toileteries (Journal Official 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953), AFNOR (1979) and OECD (1979).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Roucher SA, Couhé.
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

VEHICLE: none
Duration of treatment / exposure:
Not applicable
Observation period (in vivo):
Observations were recorded at 1 hr and 1, 2, 3, 4 and 7 days after instillation.
Number of animals or in vitro replicates:
12 males:
first group of 6 males without rinsing and secong group of 6 males with rinsing after 30s.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing carried out with Dacryoserum (from Chibert Laboratories, Paris)

SCORING SYSTEM:
According to an evaluation scale adapted from Kay & Calandra (1962). At each observation time, lesions of the conjunctiva, iris and cornea were scored separately.
The sum of these scores being the individual ocular irritation index (IOI) for each animal. Calculation of the mean (and standard deviation) of the IOI values obtained at any one time gave the mean ocular irritation index (MOI). The greatest MOI obtained over the range of observation times was identified as the acute ocular irritation index (AOI), which was used for the preliminary classification of a substance in one of six categories between "non-iritant" and extremely irritant (see Table 7.3.2/1)
Irritation parameter:
other: Acute ocular irritation index (AOI)
Basis:
mean
Remarks:
(without rinsing)
Time point:
other: 1 h
Score:
16.17
Max. score:
110
Reversibility:
fully reversible
Remarks:
Day 3
Remarks on result:
other: MOI: 0 (Day 4)
Irritation parameter:
other: Acute ocular irritation index (AOI)
Basis:
mean
Remarks:
(rinsing 30s after instillation)
Time point:
other: 1h
Score:
13
Max. score:
110
Reversibility:
fully reversible
Remarks:
Day 3
Remarks on result:
other: MOI: 1 (Day 2)
Irritant / corrosive response data:
No data
Other effects:
No data

No data.

Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: other: AFNOR (1982)
Conclusions:
Under the test conditions of this study, 1,2-diethoxybenzene is irritating to rabbits on ocular application without rinsing and slightly irritating when rinsed.
Executive summary:

In a primary eye irritation study (J.P. Guillot and al, 1982), using a procedure that complied with the main requirement of three methods (OECD, AFNOR, Cosmetic and toileteries), 0.1 mL of 1,2 -diethoxybenzene was instilled into the conjunctival sac of the eye of treated groups of 6 New Zealand white rabbits (males) (eyes washed and unwashed). Scoring was assessed at 1 hr and 1, 2, 3, 4, 7 days post instillation. Irritation was scored by the method according AFNOR.

- As the Acute Ocular irritation Index (AOI) = 16.7 and the Mean Ocular irritation Index (MOI) = 0 (Day 4), 1, 2 -diethoxybenzene was considered as irritating to rabbits on ocular application without rinsing according to AFNOR scale.

- As the Acute Ocular irritation Index (AOI) = 13 and the Mean Ocular irritation Index (MOI) = 1 (Day 2), 1, 2 -diethoxybenzene was considered as slightly irritating to rabbits on ocular application when rinsed according to AFNOR scale.

In conclusion, based on these results, 1,2 -diethoxybenzene is considered as irritating to eyes and classified into category 2A, H319 according to the CLP Regulation (EC) N° 1272/2008 and as Xi-R36 according to the Directive 67/548/EEC.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

- Skin irritation:

Only one publication was available (Guillot and al, 1982) and was performed according to three methods (OECD, AFNOR, Cosmetic and toiletries).

The test performed according to OECD method, was selected as the key study with reliability 2 according to Klimisch rating (Kr)

The other two tests were considered as supporting studies (Kr: 4).

Groups of 6 male New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted o-Diethyoxybenzene to the dorsal surface of the trunk (skin was clipped (OECD method) and clipped + scarified (AFNOR + Cosmetic methods) before application) ) for 4 hours (OECD and AFNOR) and for 23 hours (Cosmetic) under an occlusive dressing. Skin reactions were assessed 1, 48 and 1, 24, 48 and 1, 24, 48, 72 hours after patch removal for Cosmetic, AFNOR and OECD respectively using the Draize scale. The irritancy of the test item was then defined on the basis of the primary dermal irritation index (PDII) using the AFNOR and Cosmetic scale.

PDII (OECD) is 0.21, PDII (AFNOR) is 0.17 and PDII (Cosmetic) is0.42.Based on all these results, o- Diethoxybenzene is considered as not irritating to skin.

- Eye irritation:

One study was available with reliability 2 according to Klimisch rating. This study is considered as the key study despite the limited level of details. Indeed, it highlights the irritating properties of the substance.

In a primary eye irritation study (J.P. Guillot and al, 1982), using a procedure that complied with the main requirement of three methods (OECD, AFNOR, Cosmetic and toileteries), 0.1 mL of 1,2 -diethoxybenzene was instilled into the conjunctival sac of the eye of treated groups of 6 New Zealand white rabbits (males) (eyes washed and unwashed). Scoring was assessed at 1 hr and 1, 2, 3, 4, 7 days post instillation. Irritation was scored by the method according AFNOR.

- As the Acute Ocular irritation Index (AOI) = 16.7 and the Mean Ocular irritation Index (MOI) = 0 (Day 4), 1, 2 -diethoxybenzene was considered as irritating to rabbits on ocular application without rinsing according to AFNOR scale.

- As the Acute Ocular irritation Index (AOI) = 13 and the Mean Ocular irritation Index (MOI) = 1 (Day 2), 1, 2 -diethoxybenzene was considered as slightly irritating to rabbits on ocular application when rinsed according to AFNOR scale.

In conclusion, based on these results, 1,2 -diethoxybenzene is considered as irritating to eyes.


Justification for selection of skin irritation / corrosion endpoint:
key study selected.

Justification for selection of eye irritation endpoint:
This study is considered as the key study despite the limited level of details. Indeed, it highlights the irritating properties of the substance.

Effects on eye irritation: irritating

Justification for classification or non-classification

- Skin irritation:

As PDII is 0.21, the test substance is considered as non-irritant to the skin. Based on these results, no classification for skin irritation is required according to the CLP Regulation (EC) N° 1272/2008 and the Directive 67/548/EEC criteria.

- Eye irritation:

As the Acute Ocular Irritation Index (AOI) is 16.7 and the mean Ocular Irritation Index (MOI) is 0 (Day 4), 1,2 -diethoxybenzene is considered as irritating to rabbits on ocular application and classified into category 2A, H319 according to the criteria of the CLP regulation (EC) N°1272/2008 and as Xi-R36 according to the Directive 67/548/EEC criteria.

- Respiratory irritation:

No classification is possible due to lack of data.