Registration Dossier

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:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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 pharmacotoxic signs on day 1, and continued to remain normal during the remainder of the 14-day observation period
Body weight:
Body weights at days 0 and 14 were within a normal range for both male and female animals.
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.