Diethylbenzene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Remarks:

Not specified in report.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: FIFRA Subdivision F; TSCA

Principles of method if other than guideline:

Method: T03-03:EPA OPP 81-1; FIFRA Subdivision F; TSCA

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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

MCS 2313

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Breeding Laboratories Wilmington, Massachusetts -  Sprague-Dawley rats - Age:  9 to 12 weeks of age - Weight at study initiation: 292 to 355 grams for males, and 224 to 253  grams for females

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: DHEH Publication No. (NIH) 78-23 Revised 1978

Housing: Group housing(six/cage) during equilibration. Individually housed during study.

Cages: Suspended, stainless steel with wire mesh bottoms.

Environmental Conditions: Temperature: 67-76F is considered an acceptable tmperature range for rats; 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 rats; 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 an automatic timer).

Food:Purina Laboratory Chow, #5002, ad libittum

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 randimly 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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was administered by oral intubat!on, using a ball-tipped intubation needle fitted onto a syringe. Doses were calculated using fasted body weights.

Doses:

1700, 2500, 3500 and 5000 mg/kg

No. of animals per sex per dose:

5/sex/dose (Total- 20 rats)

Control animals:

no

Details on study design:

A slngle dose was administered to each animal followed by 14 days of observations. Following a range- finding study the definitive study was conducted with 5 animals/sex/dose given 1700, 2500, 3500 or 5000 mg/kg. Anlmals were fasted overnight ( for approximately 18 hours) prior to treatment. The material was admisistered as received; no preparation was necessary. The test material was administered by oral intubat!on, using a
ball-tipped intubation needle fitted onto a syringe. Doses were calculated using fasted body weights.

The following observations were made: viability checks- twice daily, observations of pharmacologic and toxicologic signs- ~1, 2, and 4 hours after dosing and daily thereafter for fourteen days, body weights- pre-fast, post fast (just prior to dosing, weights used for calculation of doses), day 7 and day 14. Gross postmortem examinations were performed on all animals which died or were found dead during the study. At termination of the observatio period (day 14), all surviving animals were killed by carbon dioxide inhalation and examined grossly. All abnormalities were recorded but no tissues were saved.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 050 mL/kg bw

Based on:

test mat.

95% CL:

1 770 - 2 330

Mortality:

See below

Clinical signs:

other: other: A variety of abnormal signs occurred on the day of dosing.   Several animals exhibited hypoactivity, red nasal discharge, urinary  staining, partially closed eyes, prostration, and decreased food  consumption.  Signs seen in a few animals (in most 

Gross pathology:

Postmortem  examinations of animals, which were found dead, revealed a variety of  changes, primarily blue pigmentation of all/most soft tissues and/or blue  fluid in the gastrointestinal tract and urinary bladder.  Other changes  seen in most animals, which were found dead included changes in the  stomach, intestine and urinary bladder which were suggestive of an  irritant and/or corrosive effect (red or black walls, the presence of red,brown, or black fluid), discoloration of lungs, accentuated lobular pattern of the liver and red fluid in the abdominal cavity. Other changes in animals found dead appeared to represent autolytic changes or antemortem stress (testes in the body cavity). Changes in animals killed after 14 days included blue pigmentation of the brain and testes and dilated renal pelvis; other changes were simiiar to those seen in control animals in this laboratory killed by carbon dioxide inhalation or were considered to represent normal physiological variation.

Other findings:

None

Any other information on results incl. tables

Number of deaths: 
mg/kg        deaths (d; m/f)
1700        1/5 (d 3;m); 1/5 (d 6;f)
2500        5/5 (d 2;m); 4/5 (d 1-3;f)
3500        5/5 (d 1-3;m); 5/5 (d 1-5;f)
5000        5/5 (d 1-2;m); 5/5 (d 1-3;f)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 value: = 2050 mg/kg (confidence range 1770 to 2330 mg/kg)

Executive summary:

A single dose was administered to each animal followed by 14 days of observations. Following a range- finding study the definitive study was conducted with 5 animals/sex/dose given 1700, 2500, 3500 or 5000 mg/kg. Anlmals were fasted overnight ( for approximately 18 hours) prior to treatment. The material was admisistered as received; no preparation was necessary. The test material was administered by oral intubation, using a ball-tipped intubation needle fitted onto a syringe. Doses were calculated using fasted body weights.

The following observations were made: viability checks- twice daily, observations of pharmacologic and toxicologic signs- ~1, 2, and 4 hours after dosing and daily thereafter for fourteen days, body weights- pre-fast, post fast (just prior to dosing, weights used for calculation of doses), day 7 and day 14. Gross postmortem examinations were performed on all animals which died or were found dead during the study. At termination of the observatio period (day 14), all surviving animals were killed by carbon dioxide inhalation and examined grossly. All abnormalities were recorded but no tissues were saved.

The acute oral LD50 was determined to be 2050 mg/kg (confidence range 1770 to 2330 mg/kg) in rats.