Isooctyl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 october 1983 - 20 October 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

not specified

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl acetate

EC Number:

250-701-2

EC Name:

Isooctyl acetate

Cas Number:

31565-19-2

Molecular formula:

C10H20O2

IUPAC Name:

Acetic acid, isooctyl ester

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Exxon

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms Inc., Germantown NY
- Age at study initiation: Approximately 11-12 weeks
- Weight at study initiation: 193-356 g
- Fasting period before study: 18 hr
- Housing: Group housed by sex, 5 per cage (Suspended stainless steel)
- Diet (e.g. ad libitum): Purina Certified Rodent Chow, ad libitum.
- Water (e.g. ad libitum): Automatic watering system, ad Iibitum.
- Acclimation period: 30 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 40-70 %
- Photoperiod (hrs dark / hrs light): 12 hr light/dark


IN-LIFE DATES: From: 6 October 1983 To: 20 October 1983

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg

Doses:

5000 mg/kg/bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: 1, 2, 4, and 6 hours after dosing, and once per day thereafter for a total of 14 days.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

The means and standard deviations of the body weights were calculated

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Remarks on result:

other:

Remarks:

5 animals (3 males and 2 females) died following treatment with 5000 mg/kg of the test substance. LD50 was not calcualted.

Mortality:

Four animals (3 males and 2 females) were found dead on day 3.

Clinical signs:

Ano-genital staining was commonly observed in the test animals. Other in-life observations included hypoactivity, alopecia A/G area, urinary staining, unthrifty coat, hypothermia, prostration, oral discharge, alopecia abdomen, dry rales, dyspnea, alopecia both eyes, soft stool, fecal staining, and wet rales.

Body weight:

All surviving animals displayed an increase in body weights over their pre-dose weights.

Gross pathology:

Gross necropsy observations of all animals that succumbed prior to Day 14 revealed vascularized brain, distended and fluid filled cecums, fluid filled small intestine, discolored livers, lungs, thymus and kidneys, distended stomach, dark red gelatinous material present in the heart, and staining of the ano-genital area . Gross necropsy examinations at Day 14 revealed alopecia of the ano-genital area and discolored lungs.

Other findings:

- Other observations: In the opinion of the Study Director, signs of pulmonary irritation such as focal discoloration and mottling are typical findings as a result of carbon dioxide asphyxiation.

Any other information on results incl. tables

.

Applicant's summary and conclusion

Interpretation of results:

other:

Conclusions:

5 animals (3 males and 2 females) died following treatment with 5000 mg/kg of the test substance.
LD50 was not calcualted.

Executive summary:

The acute toxicity of MRD-83-303 was evaluated when administered by the oral route at 5,000 mg/kg of fasted body weight to 5 male and 5 female rats. The animals were fasted for approximately 18 hours prior to administration of the test material.

Observations were made as to the nature, onset, severity, and duration of toxicological signs 1, 2, 4 and 6 hours after dosing, and once per day thereafter for a total of 14 days. Body weights were recorded the day prior to dosing (pretest), on the day of dosing (Day 0), on Day 7, and on Day 14. Body weights of animals that died prior to Day 14 were also recorded. After the Day 14 observations, all surviving animals were weighed and euthanized by carbon dioxide asphyxiation. Gross necropsies were performed on all animals by qualified personnel.

Five animals, 3 males and 2 females, died prior to study termination. Body weights of all surviving animals increased over the 14 Day test period.

In-life observations included staining A/G area, hypoactivity, alopecia A/6 area, urinary staining, unthrifty coat, hypothermia, prostration, oral discharge and alopecia of the abdomen. A low incidence of dry rales, dyspnea, alopecia of both eyes, soft stool, fecal staining, and wet rales was also noted.

Postmortem gross examination revealed gastro-intestinal abnormalities for all animals which died prior to study termination. Liver and brain abnormalities were also frequently noted for these animals.

Necropsy observations for the animals which survived to study termination was limited to ano-genital area alopecia and lung discoloration.