4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 18, 1978 - September 15, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

EC Number:

201-328-9

EC Name:

4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

Cas Number:

81-14-1

Molecular formula:

C14H18N2O5

IUPAC Name:

1-(4-tert-butyl-2,6-dimethyl-3,5-dinitrophenyl)ethanone

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: IFF; (CS) HRH-06-190; Off-white, crystalline powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, PA, USA
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Weight at study initiation: 150-200g
- Fasting period before study: 12 hours prior to dosing
- Housing: Individually in suspended, wire-bottomed, stainless steel cages
- Diet: Purina rat chow ad libitum
- Water: ad libitum
- Acclimation period: Minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23.3°C
- Humidity: 45-55%
- Photoperiod: artificial light cycle of 12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.8 ml/100 gm body weight, equivalent to 5000 mg/kg bw

Doses:

The 5 doses levels evaluated in the initial range-finding study (2 males/2 females) were not disclosed. The single dose level evaluated in the main study was 5000 mg/kg bw.

No. of animals per sex per dose:

2 rats/sex/dose in the initial range-finding study.
5 rats/sex/dose in the main study.

Control animals:

no

Details on study design:

-Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for pharmacotoxic signs at 1, 3, and 6 hours following intubation, and daily thereafter. Bodyweights were measured prior to dosing and 14.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

An initial range-finding study evaluated 5 doses levels in 2 males and 2 females (doses were not disclosed). No deaths were reported in the range finding study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality was observed in male or female rats during the study.

Clinical signs:

other: All animals exhibited sedation and/or piloerection at 1 hour following intubation, and tremors, some sedation, and respiratory abnormalieies (depression and short, rapid respiration) at 3 and 6 hours following intubation. test animals showed no pharmacoto

Gross pathology:

A single animal had an enlarged spleen. Otherwise, no gross pathological organ changes were observed in any animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in Sprague-Dawley rats, the LD 50 (male/female) was > 5000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (55049), Sprague-Dawley rats (5/dose/sex) were given musk ketone in corn oil by gavage at doses of 5000 mg/kg bw and observed for 14 days.

LD50 (male/female): was >5000 mg/kg bw.

No mortality was observed in male or female rats during the study. All animals exhibited sedation and/or piloerection at 1 hour following intubation, and tremors, some sedation, and respiratory abnormalities (depression and short, rapid respiration) at 3 and 6 hours following intubation. Test animals showed no toxic signs on day 1, and continued to remain normal during the remainder of the 14-day observation period. Body weights at days 0 and 14 were within a normal range for both male and female animals. A single animal had an enlarged spleen; otherwise, no gross pathological organ changes were observed in any animals.