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Administrative data

acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
According to OECD 425 guideline; under GLP conditions. The substance cited in section 1.1 (identification) and the structural analogue used in this study differ only in their regiochemistry. Both compounds possess similar chemical functional groups (aromatic carbon and aromatic carbon attached to chlorine) and are therefore expected to possess similar chemical reactivities. This study has been performed using 3-chloro-o-xylene as the test material but it is expected that the test substance will produce a similar result.

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
Test type:
up-and-down procedure
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): 3-chloro-o-xylene
- Molecular formula (if other than submission substance): C8H9Cl
- Molecular weight (if other than submission substance): 140.61
- Physical state: Liquid
- Storage condition of test material: Room temperature, dry place
- Other: Stable under recommended conditions of storage and handling.

Test animals

other: Outbred albino rat (Rattus norvegicus)
Details on test animals or test system and environmental conditions:
- Source:Harlan, Indianapolis, IN
- Age at study initiation: at least 49 days old
- Weight at study initiation: 201.5 - 247.5 grams
- Housing: Housed individually in polycarbonate cages.
- Diet (e.g. ad libitum): TEK 7012 Rodent Diet, Harlan Teklad, Madison WI, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Minimum of 5 days under the same conditions as the main test.

- Temperature (°F): 68 +/- 5
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod: 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on oral exposure:
Test material is a liquid and did not require further preparation prior to dosing. The volume administered did not exceed 1ml/100g body weight.
2000 mg/kg
No. of animals per sex per dose:
Control animals:
Details on study design:
- Clinical observations were observed at least twice daily on the day of dosing (frequency of observation was determined according to the response of the test animal to the treatment). Animals were observed daily for 14 days for clinical signs. Cageside observations include: changes in the the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Animals found dead were necropsied as soon as possible (no later than 12 hours). Gross necropsies were performed on all animals whether found dead in extremis or sacrified (by CO2 inhalation) at the end of the study and gross pathological changes were recorded.
- Animals were weighed on Day 0 prior to treatment, day7, day 14 and at death.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
3 of the 5 animals survived the duration of the study. 2 of the 5 animals died during the observation period (on day 4 and 12).
Clinical signs:
other: In 4 of the 5 animals, no signs of toxicity were observed. In one animal piloerection was observed 4 hours after treatment.
Gross pathology:
No unusual findings were observed during the necropsy of all dosed animals.

Any other information on results incl. tables

Input of the results into the statistical program (AOT425StatPgm) developed by the US Environmental Protection Agency, suggests that the test material has an LD50 of > 2000 mg/kg.

Analogue approach justification:  

The test substance 4-chloro-o-xylene and the structural analogue, 3-chloro-o-xylene differ only in their regiochemistry i.e. in the position of the chlorine atom on the ring. These compounds possess similar chemical functional groups (aromatic carbon and aromatic carbon attached to chlorine) and are therefore expected to possess similar chemical reactivities. This study has been performed using 3-chloro-o-xylene as the test material but it is expected that the 4-chloro-o-xylene will produce a similar result.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Migrated information Criteria used for interpretation of results: expert judgment
Under the conditions of this study, the test material has been determined as having an acute oral LD50 of >2000 mg/kg.
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Outbred Albino rats. The study was performed to GLP and the method was designed to meet the requirements of OECD Guidelines for Testing of Chemicals No. 425 “Acute Oral Toxicity - Up and Down procedure”.

The test material was administered orally, after overnight fasting, once only by intragastric intubation. The administered volume did not exceed 1ml/100g body weight. Following a preliminary test in which a single female was dosed with the test material at 2000 mg/kg body weight, there was no mortality. Accordingly, an additional four females were given the same dose of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All females were subjected to gross necropsy after an observation period of 14 days.

Two out of five females died during the study. In four out of five females, no signs of toxicity were observed during the study. One female exhibited piloerection within 4 hours of test substance administration. Females that survived the duration of the study showed expected gains in bodyweight. No abnormalities were noted at necropsy. The statistical computer program (AOT425StatPgm) estimated an acute oral median lethal dose (LD50) of the test material in the female Outbred Albino rats as greater than 2000 mg/kg bodyweight.