Registration Dossier

Administrative data

Description of key information

- Acute toxicity: oral: LD50 (rat): > 2000 mg/kg bw (Kr: 2, Rhodia data). 1,2-diethoxybenzene is considered as not harmful if swallowed.
- Acute toxicity: dermal: no data available
- Acute toxicity: inhalation: no data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 26 July 2005 to 02 August 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Screening test of OECD 423.The observation period was reduced to 7 days, the body weight was recorded on days 1 and 8 only and no macroscopic necropsy examinations were performed.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
: the observation period was reduced to 7 days, the body weight was recorded on days 1 and 8 only and no macroscopic necropsy examinations were performed (screening test)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
: the observation period was reduced to 7 days, the body weight was recorded on days 1 and 8 only and no macroscopic necropsy examinations were performed (screening test)
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the animals will be approximately 8 weeks old.
- Weight at study initiation: 180 to 220 g within a range of +/-20% of the mean body weight.
- Fasting period before study: the animals will be fasted during the night before treatment but will have free access to water. Food will be given back
approximately 4 hours afetr administration of the test item.
- Housing: the animals will be housed in polycarbonate cages with stainless steel lid. Each cage will contain one to seven animals during the acclimation period and three rats of the same group during the treatment period.
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non recycled air.
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no.: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: taking into account information provided by the sponsor, the starting dose-level was 2000 mg/kg bw.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: the animals were observed 30 minutes after dosing, periodically during the first 24 hours and then daily
(including weekends and public holidays) for a period of 8 days.The body weight was recorded on days 1 and 8.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight and body weight gain.
Statistics:
Not performed.
Preliminary study:
No mortality was observed in this screening test performed with three female rats at 2000 mg/kg bw. Therefore, the oral LD50 of o-Diethoxybenzene was higher than 2000 mg/kg in rats.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was recorded during the study (See Table 7.2.1/2)
Clinical signs:
Hypoactivity, piloerection and dyspnea were observed in all animals from day 1 up to day 2 in the morning. No clinical signs persisted from day 2 in
the evening up to the end of the observation period (day 8).
Body weight:
The overall body weight gain of the animals was not affected by treatment with the test item.
Gross pathology:
No macroscopic examinations were performed.
Other findings:
No data

Table 7.2.1/2: Number of animals dead 

Dose
(mg/kg bw)

Mortality (# dead/total)

Male

Female

Combined

2000

 -

0/3 

0/3 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions of this study, the oral LD50 of o-Diethoxybenzene was higher than 2000 mg/kg in female rats. Based on these results, no classification is warranted according to the criteria of the CLP Regulation (EC) N°1272/2008 and of the Directive 67/548/EEC.
Executive summary:

The acute oral toxicity of o-Diethoxybenzene was determined in an acute toxic class screening assay (C.Pelcot, 2005). The test item was prepared in corn oil and was administered to three female rats (SD) at the dose-level of 2000 mg/kg bw, under a volume of 10 mL/kg. Clinical signs, mortality and body weight gain were checked for a period of up to 7 days following the single administration of the test item. No macroscopic examinations were performed.

No mortality was recorded during the study. Hypoactivity, piloerection and dyspnea were observed in all animals from day 1 up to day2 inthe morning. No clinical signs persisted from day2 inthe evening up to the end of the observation period (day 8). The overall body weight gain of the animals was not affected by treatment with the test item.

Under the test conditions of this study, the oral LD50 of o-Diethoxybenzene was higher than 2000 mg/kg in rats. Based on these results, no classification is warranted according to the criteria of the CLP Regulation (EC) N°1272/2008 and of the Directive 67/548/EEC.

 

This acute oral study (screening) is classified as acceptable. It satisfies the guideline requirement for an acute oral study in the rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Screening test of OECD 423 and has Klimisch score 2

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

1- Acute oral toxicity:

Two studies were available with reliability 2 according to Klimisch rating (Kr)

- A study report (C.Pelcot, 2005) has been chosen as key study for this endpopint (Kr: 2). This study was conducted similarly to OECD guideline 423 (screening test) and not in compliance with GLP. The test item was prepared in corn oil and was administered to three female rats (SD) at the dose-level of 2000 mg/kg bw, under a volume of 10 mL/kg. Clinical signs, mortality and body weight gain were checked for a period of up to 7 days following the single administration of the test item. No macroscopic examinations were performed.

No mortality was recorded during the study. Hypoactivity, piloerection and dyspnea were observed in all animals from day 1 up to day 2 in the morning. No clinical signs persisted from day 2 in the evening up to the end of the observation period (day 8). The overall body weight gain of the animals was not affected by treatment with the test item.

Under the test conditions of this study, the oral LD50 of o-Diethoxybenzene was higher than 2000 mg/kg in rats. Based on these results, o-Diethoxybenzene is considered as not harmful if swallowed.

- A study report (J. Pasquet and A. Mazuret, 1977) has been chosen as supporting study. Groups of CD-rats (5/sex) were given a single oral dose of Ethylguethol at doses of 0 (vehicle only), 3000, 4500, 6700,10000 and 15000 mg/kg bw and observed for 15 days. Examinations for mortality, clinical signs and body weight gain were performed during the 15-day study period. All surviving animals were euthanatized and necropsied at the end of the observation period.

All animals died when treated with15000 and 10000mg/kg bw. Four animals died when dosed with 6700 mg/kg bw. No deaths occurred at 3000 and 4500 mg/kg bw. Sedation, dyspnea, decubitus with muscular hypotonia, bradypnea and cyanosis (before death) were observed. These clinical signs were not more detailed in this study. The body weight gain was not affected by treatment in animals at 3000 and 4500 mg/kg bw. At necropsy, a macroscopic examination revealed no abnormality.

Under the test conditions, the oral combined (male and female) LD50 in rats was 7250 mg/kg bw.

Taken together these results show that o-Diethoxybenzene is not harmful if swallowed

2- Acute dermal toxicity: Study is not required since the tested substance is a transported isolated intermediate (ECHA. Guidance on intermediates. Version: 2, December 2010) 3- Acute inhalation toxicity: Study is not required since the tested substance is a transported isolated intermediate (ECHA. Guidance on intermediates. Version: 2, December 2010)

Justification for selection of acute toxicity – inhalation endpoint
Study is not required since the tested substance is a transported isolated intermediate (ECHA. Guidance on intermediates. Version: 2, December 2010)

Justification for selection of acute toxicity – dermal endpoint
Study is not required since the tested substance is a transported isolated intermediate (ECHA. Guidance on intermediates. Version: 2, December 2010)

Justification for classification or non-classification

1- Acute toxicity: oral:

As the LD50/rat/oral is higher than 2000 mg/kg bw and no mortality and significant clinical signs observed at this dose, o- Diethoxybenzene is considered as not harmful if swallowed and not classified according to the criteria of the CLP Regulation (EC) N° 1272/2008 and the Directive 67/548/EEC.

2- Acute toxicity: dermal:

No classification is possible due to lack of data.

3 -Acute toxicity: inhalation:

No classification is possible due to lack of data.