4-chloro-o-xylene

Acute Toxicity: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-2,3-dimethylbenzene

Cas Number:

608-23-1

Molecular formula:

C8H9Cl

IUPAC Name:

1-chloro-2,3-dimethylbenzene

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

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

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.