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Diss Factsheets

Administrative data

Description of key information

ORAL

LD50 >2000 mg/kg bw, female rat, OECD 425 (Tay, 2004)

DERMAL

LD50 >2000 mg/kg bw, New Zealand Rabbit, OECD 402 (Chin, 2004)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
other: Outbred albino rat (Rattus norvegicus)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 +/- 5
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod: 12 hours light / 12 hours dark
Route of administration:
oral: gavage
Vehicle:
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.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
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.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
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.

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.

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
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. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study was conducted on a close structural analogue of the registered substance in accordance with ta standardised guideline under GLP conditions. The quality of the database is therefore considered to be good.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
According to EPA OPPTS 870.1200; OECD 402 guideline; under GLP conditions. Read-across to a structural analogue. 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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 15 weeks old
- Weight at study initiation: 2.00 - 2.36 kg
- Housing: Housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): TEK 8630 Rabbit Diet, Harlan Teklad, Madison WI, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimatization: Minimum of 5 days under the same conditions as the actual test.

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

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: approximately 10%
- Type of wrap if used: impervious bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done):Gently wiped with USP water for injection
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 rabbits of each sex (10 rabbits in total were used in this study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed frequently during the first data and subsequent clinical observations were made a least once daily. Animals were weighed at day 0 (prior to dosing), day 7 and day 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No test material related mortality occurred during this study.
Clinical signs:
other: No observations of systemic toxicity were observed during this study.
Gross pathology:
No abnormalities were discovered during the necropsies.
Other findings:
All animals exhibited slight to severe erythema and slight to moderate edema during the duration of the study. The most severe reactions were observed between days 3-7. By the end of the 14 day observation period, 7 of the 10 animals had complete reversal of reactions.

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.

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

The study was performed to assess the acute dermal toxicity of the test material in the New Zealand White strain rabbit. The study was performed to GLP and the method was designed to meet the requirements of OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” and, additionally, EPA OPPTS 870.1200 (Acute Dermal Toxicity). A limit test was performed on 10 rabbits (5 male; 5 female), 24-hour, occluded dermal application of the test material to intact skin at a dose of 2000 mg/kg body weight. Clinical signs, including skin reactions, and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths or signs of systemic toxicity. All animals exhibited slight to severe erythema and slight to moderate edema during the study. By the end of the 14 day study period, 7/10 animals had complete reversal of reactions. Animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in male and female New Zealand White rabbits was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no study available
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study was conducted on a close structural analogue of the registered substance in accordance with a standardised guideline under GLP conditions. The quality of the database is therefore considered to be good.

Additional information

Acute oral

The acute oral toxicity of 3-chloro-o-xylene, a structural analogue of the registered substance, was evaluated in female Outbred Albino rats in a GLP study conducted in accordance with OECD 425.

The test material was administered by oral gavage at a limit dose of 2000 mg/kg. Two out of five females died during the study. In four out of five females, no signs of toxicity were observed during the study. There were no other remarkable findings. The acute oral LD50 was estimated to be >2000 mg/kg bw.

 

Acute dermal

The acute dermal toxicity of 3-chloro-o-xylene, a structural analogue of the registered substance, was evaluated in male and female New Zealand rabbits in a GLP study conducted in accordance with OECD 402 and EPA OPPTS 870.1200.

The test material was administered as a single, 24-hour, occluded dermal application to intact skin. There were no deaths or signs of systemic toxicity. All animals exhibited slight to severe erythema and slight to moderate oedema during the study; by the end of the 14 day study period, 7/10 animals had complete reversal of reactions.. There were no other remarkable findings. The acute dermal LD50 was estimated to be > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral and dermal routes.