1,3,5-triisopropylbenzene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-triisopropylbenzene

EC Number:

211-941-3

EC Name:

1,3,5-triisopropylbenzene

Cas Number:

717-74-8

Molecular formula:

C15H24

IUPAC Name:

1,3,5-tris(propan-2-yl)benzene

Details on test material:

CHEMICAL NAME: 1,3,5-Triisopropylbenzene
HAEL NO.: 85-0076
EK ACC. NO.: 022223
CAS NO.: 717-74-8
SRID OR LOT NO.: X-17111-47B
EXPERIMENT NO.: 85-0076G2

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS:
Five male and five female rats (CRL:CD(SD)BR) from Charles River Breeding Laboratories, Wilmington, MA, were randomly assigned to each test group. Animals were isolated for approximately two weeks prior to testing. At the start of the study, rats were approximately 6 (males) and 8 (females) weeks old and weighed approximately 216 g (males) and 186 g (females). Rats were chosen for this study because they are a common representative species for toxicity studies.

HOUSING:
Rats were housed in groups of five segregated by sex. The study was conducted in the vivarium area of Building 320. The study room was maintained at 73 + 3 °F and 38-46% relative humidity. A photoperiod of 12 hours from 6 a.m. to 6 p.m. was maintained. A two-week study with the same compound was housed in the same room as this study. Cages and racks were washed once a week. The absorbent paper under the cages was changed daily.

FEED AND WATER:
Purina Laboratory Rodent Chow (5002) ground chow was fed ad lib. Feed containers were cleaned weekly. Feed containers were refilled at least once a week. Water was supplied ad lib. through an automatic watering system. The source of the water was the-Monroe County Water Authority. No known contaminants in feed or water were expected which would interfere with the outcome of this study.

IDENTIFICATION:
All rats were identified by a unique metal ear tag and ear punch.

RANDOMIZATION:
All culling and randomization was done by computer-generated lists using the Automated Animal Toxicology System.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Rats were given 100, 300, or 1000 mg/kg/day of the test material for 21 doses over 29 days. Doses were given five days per week including holidays. No vehicle was used. Controls received a dose of distilled water equal in volume to that of the highest test group.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

29 days

Frequency of treatment:

once daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1000 mg/kg/day
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
300 mg/kg/day
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
0 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, sham-exposed

Details on study design:

This study was conducted by methods comparable to OECD GUIDELINES for TESTING of CHEMICALS TG-407, Repeated Dose Oral ToxicityRodent:
28-day or 14-day study, and Annex V B.7. Rats were given 100, 300, or 1000 mg/kg/day of the test material for 21 doses over 29 days. Doses were given five days per week including holidays. No vehicle was used. Controls received a dose of distilled water equal in volume to that of the highest test group.

Examinations

Observations and examinations performed and frequency:

BODY AND FEED WEIGHT DETERMINATIONS:
Body weights were measured on Days 0, 4, 7, 14, 2l,and 28. Feed weights were measured on Days 4, 7, 11, 14, 18, 21, 25
and 28.

CLINICAL OBSERVATIONS:
During the morning of every working day each rat was removed from its cage and examined by a trained technician. In the afternoon, cageside observations were conducted. A cageside observation included, but was not limited to, examination of the hair, skin, eyes, motor activity, feces, and urine.

HEMATOLOGY AND CLINICAL CHEMISTRY EXAMINATIONS:
At the time of necropsy, blood was collected from the posterior vena cava while the rats were under C02 anesthesia. All assays were conducted by the Animal Clinical Analysis Group, Health & Environmental Labs (HAEL). Hematology tests included: hemoglobin concentration, hematocrit, red blood cell count, white blood cell count, differential white blood cell count, platelet count, red blood cell indices, and examination of the blood smears for cellular morphology. Clinical chemistry tests included: aspartate aminotransferase (AST), alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase, creatinine, urea nitrogen, and glucose.

Sacrifice and pathology:

Rats were fasted overnight, anesthetized with C02, and exsanguinated by severing the posterior vena cava after collecting blood for analysis. Necropsies were conducted according to pathology SOP No. TP 180. The liver and kidneys were weighed. The kidneys were weighed together. Organ/body weight ratios were calculated. The following organs were fixed in 10% buffered formalin: trachea, lungs, heart, tongue, esophagus, stomach,duodenum, jejunum, ileum, cecum, colon, pancreas, liver, salivary glands, kidneys, urinary bladder, pituitary gland, adrenal glands, thyroid glands, parathyroid glands, thymus, spleen, mesenteric lymph nodes, bone marrow (femoral), brain, testes, epididymides, male accessory sex glands, ovaries, vagina, uterus, Fallopian tubes, and gross lesions. The eyes were fixed in a modified Zenker's fixative. All tissues were examined microscopically from the control and high-dose groups and gross lesions were examined from other groups.

Statistics:

Mean values were calculated for body weight, feed consumption, organ weights, hematology, and clinical chemistries. All mean data, except feed consumption, were evaluated using the following computer-generated statistical tests: one-way analysis of variance CANOVA), Bartlett's test, and Duncan's multiple range test using a P value of < 0.05 to indicate statistical significance. Feed consumption was not analyzed statistically because the animals were group housed.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

MORTALITY:
A female rat No. 340 died from a gavage error on Day 21.

CLINICAL SIGNS:
Normal

BODY WEIGHT AND FEED CONSUMPTION:
Normal. A low dose female rat No. 330 had a reduced weight gain, however, it did not significantly affect the group'svalues.

HEMATOLOGY AND CLINICAL CHEMISTRY:
Normal. The following incidental findings were observed in male rats: a moderate increase in the number of atypical lymphocytes and a slight decrease in the number of eosinophile in the low-dose group, and a minimal anisocytosis and macrocytosis in the high-dose group; in female rats, there was a slight increase and minor clumping of platelets in a single low-dose female rat (326). A low-dose female rat, No. 330, had increased values of AST, ALT, SDH and polymorphonuclear leukocytes and decreased AP and lymphocytes.

ORGAN WEIGHTS:
Normal

PATHOLOGY:
No treatment-related changes were observed.

Effect levels

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The test material, 1,3,5 triisopropylbenzene produced no signs of toxicity in male or female rats that were treated daily with doses up to 1000 mg/kg. The no-effect dose level (NOEL) was determined to be 1000 mg/kg.

Executive summary:

In a 4 -week repeat oral dose toxicity study in rats, 1,3,5 triisopropylbenzene (TIPB) was administered daily to male and female rats

via oral gavage at doses of 100, 300, or 1000 mg/kg (control rats were given distilled water at a volume that was equivalent to that of the highest test group). Following the treatment period, there were no test material-related differences in clinical signs, body weight, feed consumption, hematology, clinical chemistry, organ weights or histopathology. A no-effect level (NOEL) for TIPB was determined to be 1000 mg/kg.