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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:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well conducted, following standard guidelines, but not GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2- Fluoronitrobenzene
- Physical state: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Animals were supplied by Bantin and Kingman Ltd., Hull, yorks.
- Age at study initiation: no data
- Weight at study initiation: 160 +/- 20 g
- Fasting period before study: yes, animals were fasted overnight prior to administration of the test material.
- Housing: The animals were segregated according to sex and housed in grid-floor cages.
- Diet: Standard pelleted laboratory animal diet (41B from E. Dixon and Son (Ware) Ltd., Herts) was provided at all times with the exception that the animals were fasted overnight prior to administration of the test material.
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % v/v (range finding assay) 10 % v/v ( final assay)



Doses:
Range finding assay: 0.8, 0.4, 0.2 and 0.1 ml/kg (corresponding to 1070, 535, 267.5 and 133.75 mg/kg bw)

Final assay: 0.40, 0.28, 0.20 and 0.1 ml/kg (corresponding to 535, 374.5, 267.5 and 187.25 mg/kg bw)

To convert the dose values the density (1.3375 g/ml) of the substance has been used: y ml/kg x 1.3375 g/ml = z g/kg bw.
No. of animals per sex per dose:
Range finding assay: 2 animals per group
Final assay: 5 males and 5 females per group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (7 days for the range finding assay)
- Frequency of observations and weighing: Animals were observed immediately following dosing and thereafter at daily interval. Body weight was monitored throughout the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Statistics:
The acute oral LD50 value, together with its 95% confidence limits, was calculated according to the method of Litchfield and Wilcoxon - A Simplified Method of Evaluating Dose - Effect Experiments - J. Pharm. Exp. Tharap. 1949, 96 99.

Results and discussion

Preliminary study:
A range-finding study was conducted involving the administration of the product at dose levels equivalent to 0.8, 0.4, 0.2 and 0.1 ml/kg (corresponding to 1070, 535, 267.5 and 133.75 mg/kg) to groups of 2 animals to determine the order of acute oral toxicity with respect to lethal effect. These animals were observed immediately after dosing and then throughout the following 7 day period. Mortality results are presented in table 1 in the field "any other information on results incl. tables".
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
320 mg/kg bw
Based on:
test mat.
95% CL:
240.75 - 414.63
Mortality:
Yes, mortality occurred during the time course of the test. For full details see table 2 in the field "any other information on results incl. tables".
Clinical signs:
Within 24 hours of dosing, animals in the higher dose groups (535 and 374.5 mg/kg bw) exhibited severe piloerection, hypotermia, coma, blood on masks and lethargy. However, those rats dosed at levels of 187.25 and 267.5 mg/kg bw displayed only slight piloerection 24 hours after dosing. All surviving rats were apparently asymptomatic by day 3 and until the end of the experiment.
Body weight:
Weight loss in certain individuals after 72 hours in the 267.5 mg/kg bw group was observed, but recovered by day 7. For full details see table 3 in the field "any other information on results incl. tables".
Gross pathology:
No gross abnormalities were observed in any of the animals selected.

Any other information on results incl. tables

Table 1: Mortality results of the range finding assay

Dose level (mg/kg bw) Deaths by day Percentage
Mortality (%)
1 2 3 4 7
1070 2/2 2/2 2/2 2/2 2/2 100
535 2/2 2/2 2/2 2/2 2/2 100
267.5 0/2 0/2 1/2 1/2 1/2 50
133.75 0/2 0/2 0/2 0/2 0/2 0

Table 2: Mortality results of the final assay

Dose level (mg/kg bw) Deaths by day Percentage
Mortality (%)
1 2 3 4 5 7 14
535 10/10 10/10 10/10 10/10 10/10 10/10 10/10 100
374.5 5/10 6/10 6/10 6/10 6/10 6/10 6/10 60
267.5 2/10 4/10 4/10 4/10 4/10 4/10 4/10 40
187.25 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0

Table 3: Group mean body weight data

Dose level (mg/kg bw) Body weight (g) at day
0 3 7 14
535 158.4 - - -
374.5 145.4 157.5 163.3 193.3
267.5 163.5 156.0 188.7 195.7
187.25 145.2 181.7 188.9 220.6

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the condtions of this test, the results indicated that the test substance should be classified as Acute oral Tox. 4, H302 (Harmful if swallowed) according to CLP .
Executive summary:

In an acute toxicity test, Wistar rats of both sexes (5 males and 5 females per group) were exposed to 2 -Fluoronitrobenzene. The sample was administered at dose levels equivalent to 535, 374.5, 267.5 and 187.25 mg/kg bw, in order to obtain the 0 - 100 % sequence of lethal effects necessary for the estimation of the acute oral LD50 value. Animals were observed immediately following dosing and thereafter at daily interval for a period of 14 days. Any deaths or other signs of toxicity were recorded.

Body weight was monitored throughout the study, and postmortem examinations were performed on selected individuals to observe any gross abnormalities in the viscera. Severe piloerection, hypotermia, coma, blood on mask, lethargy within 24 hours were observed in 535 and 374.5 mg/kg groups. Slight piloerection after 24 hours, and weight loss in certain individuals after 72 hours were observed in the 267.5 mg/kg group, otherwise all surviving rats were apparently asymptomatic by day 3 and until the end of the experiment.

Mortality occurred in all animals at the highest dose (535 mg/kg bw).

At 374.5 mg/kg bw, 60 % of mortality was observed and at the dose level of 267.5 mg/kg bw 40 % of mortality was observed. At the lowest dose (187.5 mg/kg bw), no mortality was observed.

Then, a LD50 value of 320 mg/kg bw (240.75 - 414.63 mg/kg bw) has been calculated using the method of Litchfield and Wilcoxon. Based on results of this acute test, the substance is classified as Acute oral Tox. 4, H302 (Harmful if swallowed) according to CLP.