4-formyl-2-methoxyphenyl isobutyrate

Endpoint summary

Description of key information

Key study:- Givaudan 1983: Acute oral toxicity, no guideline followed (similar to OECD 401), LD50 > 5 mL/kg bw (male and female rats).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Older study conducted prior to development of GLP and OECD guideline, however methodology is comparable to current guidelines

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

Conducted prior to development of GLP

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Isobutavan Y-09607
- Physical state: clear colourless liquid
- Received at laboratory on December17, 1982

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult, SPF bred, albino rats (Cpb:WU; Wistar random) were used. The body weights of the males varied from 92-115g, those of the females from 82-90g. The rats were acclimatized to the laboratory conditions for at least 5 days prior to the test. The rats were housed in groups of five, males and females separated in stainless steel cages with grid bottom and front in a well ventilated room, maintained at 23°C.

Relative humidity was between 30 and 70%, lighting was artifical with a sequence of 12 hours lights and 12 hours dark. Tap water was freely availiable at all times, and they recieved stock diet ad libitum, except for the overnight period before treatment, when food was withheld.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was administered undiluted by gavage

Doses:

The test substance was administered in one single dose of 5.0 mL/kg body weight (equivalent to approximately 5000 mg/kg bw)

No. of animals per sex per dose:

Five male and female rats were used

Control animals:

no

Details on study design:

After treatment, the rats were observed frequently for signs of intoxication during the first 4 hours post treatment and thereafter at least once daily throughout the 14 day observation. The indiviual body weights were determined on day 0, 7 and 14. At the end of the observation period the survivors were killed and necropsied.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 40% mortality at the limit dose

Mortality:

Two males and two females died between 6 hours and 2 days after treatment.

Clinical signs:

other: Clinical observations during the first 4 post treatment hours revealed sluggishness and rough coats. Later on, encrustations around eyes and nostrils, signs of emaciation and coma were frequently observed. The survivors were reported to recover gradually

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute oral LD50 of isobutavan was found to be greater than 5000 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of isobutavan was evaluated in 5 male and 5 female Wistar rats. The test substance was administered undiluted by gavage, at a dose of 5 mL/kg bw, equivalent to appoximately 5000 mg/kg bw. The rats were observed for mortality and signs of toxicity for 14 days after dosing. Necropsies were performed on survivors at study termination. Clinical signs of toxicity observed in the first 4 hours after administration included sluggishness and rough coats. Later, encrustations around the eyes and nostrils, emaciation and coma were frequently observed. Two males and two females died between 6 hours and 2 days after treatment. Individual bodyweights of survivors increased during the observation period. No abnormalities were detected at gross necropsy of survivors. Under the conditions of the study, the acute oral LD50 of isobutavan was found to be greater than 5000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study with a Klimisch score of 2 is sufficient for classification determination.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity of isobutavan was evaluated in 5 male and 5 female Wistar rats. The test substance was administered undiluted by gavage, at a dose of 5 mL/kg bw, equivalent to appoximately 5000 mg/kg bw. The rats were observed for mortality and signs of toxicity for 14 days after dosing. Necropsies were performed on survivors at study termination. Clinical signs of toxicity observed in the first 4 hours after administration included sluggishness and rough coats. Later, encrustations around the eyes and nostrils, emaciation and coma were frequently observed. Two males and two females died between 6 hours and 2 days after treatment. Individual bodyweights of survivors increased during the observation period. No abnormalities were detected at gross necropsy of survivors. Under the conditions of the study, the acute oral LD50 of isobutavan was found to be greater than 5000 mg/kg bw in rats.

Justification for classification or non-classification

Acute Oral Toxicity

In accordance with Regulation (EC) No. 1272/2008, the substance does not meet the GHS criteria for classification for acute oral toxicity.