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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 August 1984 to 5 September 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with recognised guideline. Although no data is available on the study's GLP compliance equivalent quality assurance methods were in place at the testing laboratory. The substance is present in an oil formulation at ca.30% and a purity correction performed to give the LD50 of the substance itself.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Remarks:
QA and study director statements included in the report
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DNBP formulation
- Physical state: brown liquid
- Analytical purity: 30 - 31.2% w/w DNBP in oil.

Test animals

Species:
rat
Strain:
other: HC/CFY (Remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: approximately four to six weeks
- Weight at study initiation: 104 to 128 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum period of 6 days prior to the start of the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C to 25°C
- Humidity (%): ca. 68%
- Air changes (per hr): approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period

IN-LIFE DATES: From 22 August to 5 September 1984.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- No vehicle used

MAXIMUM DOSE VOLUME APPLIED:
- not exceeding 0.16 ml/kg bw

Doses:
Three dose levels of 64, 100 and 160 mg/kg bodyweight
No. of animals per sex per dose:
64 mg/kg bw - 5m, 5f
100 mg/kg bw - 5m, 5f
160 mg/kg bw - 5m, 5f
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days in the main study, 5 days in the preliminary study
- Frequency of observations and weighing: Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice per day. Clinical signs were recorded at each observation.
- Necropsy of survivors performed: yes
- Other examinations performed: Approximate time of death of individual rats. The nature, severity, approximate time of onset and duration of each toxic sign were recorded, also individual bodyweights of rats on Days 1 (day of dosing), 8 and 15 and at death.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of:
Finney (1971) Probit Analysis (3rd Edition) Cambridge University Press.

Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data by fitting two parallel lines on the data (males only and females only) using the technique described by Finney (1978, Statistical Method in Biological Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for non-parallelism.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
80 mg/kg bw
Based on:
test mat.
95% CL:
64 - 97
Sex:
male
Dose descriptor:
LD50
Effect level:
80 mg/kg bw
Based on:
test mat.
95% CL:
59 - 106
Sex:
female
Dose descriptor:
LD50
Effect level:
80 mg/kg bw
Based on:
test mat.
95% CL:
59 - 106
Mortality:
Mortalities occurred amongst rats at dose levels of 64 mg/kg and above from within three to eight hours of dosing.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all treated animals included pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy and increased salivation. These signs were accompanied by: pallor of the extremities among rats of all treated groups; decreased respiratory rate among rats treated at 100 and 160 mg/kg; ptosis in one female at 160 mg/kg; increased lacrimation in two females at 160 mg/kg.
Recovery as judged by external appearance and behaviour was apparently complete by Day 5.
Body weight:
Very slight bodyweight losses were recorded for rats that died, bodyweight gains were recorded for all surviving rats on Days 8 and 15.
Gross pathology:
Autopsy revealed congestion of the lungs and pallor of the liver, kidneys and spleen among animals that died during the study. Terminal autopsy findings for animals sacrificed at the end of the study were normal.

Any other information on results incl. tables

Time and number of deaths of rats dosed orally with DNBP formulation in the main study

Sex

dose

Number of deaths in group of 5

Day

1

2 to 15

Hours after dosing

2

3

4

5

6

7

8

1st observ.

2nd observ.

m

64

1

 

 

 

 

1

 

 

 

 

100

4

 

1

 

1

2

 

 

 

 

160

5

 

5

 

 

 

 

 

 

 

f

64

1

 

 

 

 

 

 

1

 

 

100

4

 

 

2

2

 

 

 

 

 

160

5

 

1

3

 

1

 

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD 50 of the formulation has been determined to be 80 mg/kg bw in both male and female rats, which is approximately equivalent to an LD50 of 24 mg/kg bw for the active substance. The substance is therefore classified as toxic.
Executive summary:

In an acute oral toxicity study conducted in accordance with OECD method 401 and under an appropriate quality assurance system, groups of 5 male and 5 female rats were dosed with a preparation of the substance in oil, at dose levels that gave equivalent concentrations of the substance itself as 64, 100 and 160 mg/kg bodyweight; the animals were observed for 14 days after treatment. The LD50 of the substance as tested was determined to be 80 mg/kg bw to both male and female rats which is equivalent to approximately 24 mg/kg bw for the active ingredient.