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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Feb. 12, 1990 to Jun. 18, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant and guideline conform, statistical analysis for mortality effects

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981, updated guideline adopted Feb. 24, 1987
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Isobutyrophenone
EC Number:
210-275-0
EC Name:
Isobutyrophenone
Cas Number:
611-70-1
Molecular formula:
C10H12O
IUPAC Name:
2-methyl-1-phenylpropan-1-one
Details on test material:
- Name of test material (as cited in study report): Darocur 1173, stage 1.
- Lot/batch No.: record 281.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach.
- Age at study initiation: 6 to 9 weeks.
- Weight at study initiation: mean=185 g; range=175-197 g.
- Fasting period before study: The rats did not receive any food from 17 hours before up to 4 hours after treatment.
- Housing: Housed separately in Makrolon cage type 3 on mobile racks.
- Diet (e.g. ad libitum): Ad libitum (type/source of diet not reported).
- Water (e.g. ad libitum): Tap water (Südhessische Gas - und Wasser AG, Darmstadt, and Wasserwerk E. Merck, Darmstadt), ad libitum.
- Acclimation period: At least 7 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26°C.
- Humidity (%): 38-46%.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

IN-LIFE DATES: From: Feb. 23 To: Mar. 21

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.04 mL/kg.

DOSAGE PREPARATION (if unusual): Test material was undiluted.
Doses:
0, 1500, and 2000 mg/kg body weight.
No. of animals per sex per dose:
0 mg/kg (control): 5 per sex per dose.
1500 mg/kg: 5 females per dose.
2000 mg/kg: 5 per sex per dose.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Behavior and general condition of all rats were monitored for 4 - 6 hours after administration and then checked daily. All animals were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study. Rats which died in the course of the study were weighed as soon as possible after they had been found dead.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: A further 10 animals (5/sex) from another study (T 13319) served as controls for body weight development. Volume administered was 1.53 and 2.04 mL/kg. The control rats were treated with 10 mL/kg of 0.25% aqueous Methocel K4M Premium solution.
Statistics:
The data were processed by the Department of Technical and Scientific Data Processing of E. Merck, Darmstadt.
1) Analysis of body weight development:
The body weight development of each rat and group was determined. The group mean value and the difference to the previous value, expressed as percentage, were calculated for each measurement and printed out on tables.
2) Mortality:
The time of death was recorded for each animal, and the number of animals which had died up to 10 different time points was listed separately for each sex and dose level on tables.
3) Calculation of the LD50:
The LD values (LD50- LD95) were determined by logit analysis, separately and jointly for each sex, and were printed out on tables.

Results and discussion

Preliminary study:
Not applicable.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 167 mg/kg bw
95% CL:
1 718 - 2 732
Remarks on result:
other: None
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: None
Sex:
female
Dose descriptor:
LD50
Effect level:
1 946 mg/kg bw
95% CL:
1 734 - 2 185
Remarks on result:
other: None
Mortality:
Mortality occurred from 23 hours after treatment until day 3 of the study.
Clinical signs:
Clinical signs occurred within 1-15 minutes after treatment and lasted up to day 4. The symptoms were: Dyspnea, locomotor disturbance, abdominal and lateral position, piloerection, increased lacrimation, rhinorrhea and epistaxis.
Body weight:
Reduction of body weight was mainly observed on day 2 of the study.
Gross pathology:
1) Animals which died:
Two of the rats that died showed inspissation and congestion of feaces in the cecum. The third rat was without gross pathological findings.
2) Animals which were sacrificed:
In the animals which were sacrificed at the end of the observation period, no organ alterations were found.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information