Diethylbenzene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Remarks:

Not specified in report.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: TSCA (Toxic Substances Control Act): Health Effects Test Guidelines; Office of Toxlc Substances; OffIe of Pestlcldes and Toxic Substances; United States Envlromntal Protection Agency, August 1982; Acute Exposure, Demal Toxlclty.

Deviations:

no

Remarks:

Not specified in report

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diethylbenzene

EC Number:

246-874-9

EC Name:

Diethylbenzene

Cas Number:

25340-17-4

Molecular formula:

C10H14

IUPAC Name:

diethylbenzene

Details on test material:

IUCLID4 Test substance: as prescribed by 1.1 - 1.4

TS: DEB Mixed isomers

IUCLID4 Test substance: as prescribed by 1.1 - 1.4

MCS 2313

Purity:Not stated
Density 0.8705 g/ml
Reference No.: NBP 3494320
Appearance: Clear colorless liquid
Purity:Not stated
Density: 0.8705 g/ml

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: New Zealand white rabbit; Hazleton-Dutchland Laboratory  Animals, Denver, PA

At start of the experiment, animals were at least 8 weeks old.   The males weighed between 2.3-2.6 kg, and the females weighed between  2.6-2.7 kg. 
 Room temperature was 60-70 F, and relative humidity was  between 30-70% during the study.  Animals were observed for 14 days  postdose.  The light cycle was 12 hours light, 12 hours dark.  Food and  water were provided ad libitum.

Observations : All animals were checked for viability twice daily. Prior to assignment to study all animals were examined to ascertain suitability for study.

Husbandry: Currently acceptable practices of good animal husbandry were followed, e.g. Guide for the Care and Use of Latoratory Animals: DHEW Publication No. (NIH) 78-23 Revised 1978

Housing: Individually housed during study.

Cages: Suspended, stainless steel

Environmental Conditions: Temperature: 60-70F is considered an acceptable tmperature range for rabbits; room temperature was monitored and recorded twice daily and maintained within this range to the maximum extent possible.

Humidity: 30-70% is considered an acceptable humidity range for rabbits; room humidity was monitored and recorded daily and maintained within this range to the maximum extent possible.

Light Cycle: 12 hours light, 12 hours dark (controlled by a n automatic timer).

Food:Lab Rabbit Chow HF, (Purina #5326), ad libitum

Water: Automatic watering system, ad libitum. Municipal water supply (Elizabethtown Water Co.)

Contaminants: There were no known contaminants reasonably expected to be found in food or water which would interfere with the results of this study.

Identification: Each animal was identified with a monel eat tag, bearing a unique number, prior to testing.

Selection: Animals were randomly placed in cages upon receipt, and were placed on study as available at the time of study initiation. Any animals considered unsuitable because of poor health or outlying body weights were excluded.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION: 
Area covered:  Intact skin of the dorsal area of the trunk.  
Occlusion: Yes. Animals wore Elizabethan collars.
Vehicle: None
Concentration in vehicle: undiluted  
Total volume applied: 5.7 ml/kg
Doses: 5000 mg/kg
Removal of test substance: Wiped free of excess test material.  Additional information is not available.

Duration of exposure:

Single dose

Doses:

5000 mg/kg

No. of animals per sex per dose:

5/sex/dose (total: 10 rats)

Control animals:

no

Details on study design:

Duration of study: A slngle dose was administered to each animal, followed by 14 days of observations.

Route of Administration: Dermal, to the cllpped intact skin of the dorsal area of the trunk.

Justification for Route of Administration: The study was intended to provlde information on the health hazards likely to arise from a short term accidental exposure to the test material by the dermal route.

Preparatlon of Animals: On tho day before doslng the halr of each rabbit was closely clipped from the dorsal area of the trunk with an electric cllpper, so as to expose at least 10% of the body surface area. Care was taken to avold abrading the skin. Only anlmals with intact, healthy skin were used.

Preparation of Test Material: The test material was used as received; no preparation was necessary.

Administration of Test Material: The material was applied directly on to the exposed skin of the animal and spread evenly over the entire area. Gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve designed to contain the test material without leakage or undue pressure. The sleeve was secured with tape and Elizabethan collars were placon all animals to prevent ingestion of the test material or disruption of the wrappings.

Following approximately24 hours of exposure, the wrappings were removed and the test site wiped free of excess test material.

Viability Checks: Twice daily

Observations of Pharmacologic and Toxicologic Signs: Approximately 1, 2. and 4 hours after dosing and daily thereafter for fourteen days.

Body Weights: Pre-test (at the time of clipping), Predose (weights used for calculation of doses) and Day 7 and Day 14

POSTMORTEM: At termination of the observation period (day 14), all animals were killed by an intravenous overdose of sodium pentobarbital and exrained grossly. All abnormalities were recorded but no tissues were saved.

Statistics:

None

Results and discussion

Preliminary study:

None

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: other: Except for fissuring exhibited at a small portion of the dose site, in  one animal, no severe dermal effects were seen. Decreased food consumption was exhibited by all ten animals on the day after dosing; by four animals on Day 4; and by one animal

Gross pathology:

Gross postmortem observations were similar to those seen in control animals in this laboratory or were considered to represent normal physiological variation.

Other findings:

Potential target organs: None
Sex Specific Differences:  None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 > 5000 mg/kg bw.

Executive summary:

This study was conducted to evaluate the acute dermal toxicity of MCS 2313 in rabbits following a single application of 5000 mg/kg of test material to the intact skin.

The acute dermal LD50 in rabbits is >5000 mg/kg.