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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
25 July 1996 to 27 August 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to internationally accepted guideline and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes
Test type:
fixed dose procedure

Test material

Constituent 1
Reference substance name:
dienone
IUPAC Name:
dienone
Details on test material:
- Name of test material (as cited in study report):Dienone
- Substance type: off-white powder
- Physical state: solid
- Analytical purity: 99.5% (by DSC)
- Lot/batch No.: Y08696/002 C166/1
- Storage condition of test material: Ambient temperatures in the dark

Test animals

Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Rodent Breeding Unit, Zeneca Pharmaceuticals, Alderly Park
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
TEST ANIMALS
- Source:
- Age at study initiation:8-9 weeks
- Weight at study initiation: males: 255-339g and females 186-245g
- Fasting period before study: yes, overnight, immediately prior to dosing.
- Housing:maxium 5 rats per group were housed per cage, sexes separately, in multiple rat racks suitable for animals of this strain and the weight range expected during the course of the study. The males at the top dose-level were singly housed from day 2 onwards, due to aggressive behaviour.
- Diet (e.g. ad libitum): PCD, supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: 6 days at laboratory, prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21+/- 2 deg C
- Humidity (%): 40-70%
- Air changes (per hr):25-30 changes/hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:10 ml/kg

MAXIMUM DOSE VOLUME APPLIED:10 ml/kg

Doses:
2000 mg/kg; 500 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:observations daily (also, once within 2 hrs, and between 4-7 hours after dosing); bodyweight: Days -1, 1, 2, 3, 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
500 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion

Conclusions:
Although one female was found dead following a dose of 500 mg/kg, no significant signs of toxicity were seen in the remaining animals at this dose-level. In addition, as there were no signs of toxicity seen in this animal prior to death, its death is thought to be unrelated to treatment. The discriminating dose for dienone is therefore considered to be 500mg/kg to male and female rats. By read-across, didenac is also considered to generate a discriminating dose of 500 mg/kg.
Executive summary:

There are no available acute toxicity studies on didenac. Results of a study conducted with a structurally similar compound (dienone) are reported and used for read-across.