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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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 but not under GLP. No negative controls.

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 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no negative controls
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
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: no
- Housing: The animals were housed separately during the 24 hour contact period, and thereafter according to dosage group and sex, in grid-floor cages.
- Diet: Standard pelleted laboratory animal diet (41B from E. Dixon and Son (Ware) Ltd., Herts) was provided ad libitum.
- 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

Administration / exposure

Type of coverage:
occlusive
Vehicle:
maize oil
Details on dermal exposure:
TEST SITE
- Area of exposure: the back and flanks of each animal.
- Type of wrap if used: Immediately after administration the trunk of the rat was encircled by a strip of impermeable adhesive tape lined with aluminium foil, to occlude the application site.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After a contact period of 24 hours the occlusive strip was removed and the contaminated area of skin cleansed of residual test material as far as possible by wiping with a soluion of detergent and warm water. The site was then rinsed and dried.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.25 ml/100 g body weight
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
Range finding assay: 1, 0.5 and 0.25 ml/kg (corresponding to 1337, 669 and 334 mg/kg bw)

Final assay: 0.70, 0.50, 0.35 and 0.25 ml/kg (corresponding to 936, 669, 468 and 334 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 (main test) 7 days (range finding study)
- Frequency of observations and weighing: The animals were inspected at daily intervals for a period of 14 days after dosing. Any deaths and other signs of toxicity were recorded, and body weight was also monitored throughout the experimental period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Statistics:
The acute dermal 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 1, 0.5 and 0.25 ml/kg (corresponding to 1337, 669 and 334 mg/kg) to groups of 2 animals to determine the order of acute dermal 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:
535 mg/kg bw
Based on:
test mat.
95% CL:
428 - 669
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:
At 936, 669 and 468 mg/kg bw, ataxia, marked piloerection, salivation, hypotermia, diuresis, chromodacryorrhoea, blood on masks and coma were observed within 24 hours of dosing. In general, animals surviving beyond day 4 of the test were apparently asymptomatic by that time. At 334 mg/kg bw, piloerection, loss of activity, hypotermia, salivation, blood on mask and chromodacryorrhoea were exhibited 24 hours after administration of the test material.
Body weight:
Individuals in the groups at 936 and 468 mg/kg bw exhibited weight loss at day 3 of the test period. However, the majority of these rats showed normal weight gain by day seven of the experiments.
Gross pathology:
The lung of all the animals examined were found to be congested with blood. Certain individuals exibited discolouration of the liver which may possibly have been due to autolysis.
Other findings:
None

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
1337 2/2 2/2 2/2 2/2 2/2 100
669 2/2 2/2 2/2 2/2 2/2 100
334 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
936 5/10 8/10 9/10 9/10 9/10 9/10 9/10 90
669 3/10 7/10 7/10 7/10 7/10 7/10 7/10 70
468 2/10 4/10 4/10 4/10 4/10 4/10 4/10 40
334 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
936 162.7 150.0 168.0 186.0
669 158.2 170.7 197.3 231.3
468 162.5 150.5 187.3 214.7
334 154.7 166.8 180.3 212.9

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the conditions of this test, the results indicated that the test substance should be classified as Acute dermal Tox. 3, H311 (Toxic in contact with skin) 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 936, 669, 468 and 334 mg/kg bw, in order to obtain the 0 - 100 % sequence of lethal effects necessary for the estimation of the acute dermal 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. At 936, 669 and 468 mg/kg bw, ataxia, marked piloerection, salivation, hypotermia, diuresis, chromodacryorrhoea, blood on masks and coma were observed within 24 hours of dosing. In general, animals surviving beyond day 4 of the test were apparently asymptomatic by that time. At 334 mg/kg bw, piloerection, loss of activity, hypotermia, salivation, blood on mask and chromodacryorrhoa were exhibited 24 hours after administration of the test material. Individuals in the groups at 936 and 468 mg/kg bw exhibited weight loss at day 3 of the test period. However, the majority of these rats showed normal weight gain by day seven of the experiments. The lung of all the animals examined were found to be congested with blood. Certain individuals exibited discolouration of the liver which may possibly have been due to autolysis. Mortality occurred in 90 % of animals at the highest dose (936 mg/kg bw). At 669 mg/kg bw, 70 % of mortality was observed and at the dose level of 468 mg/kg bw 40 % of mortality was observed. At the lowest dose (334 mg/kg bw), no mortality was observed. Then, a LD50 value of 535 mg/kg bw (428 - 669 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 dermal Tox. 3, H311 (Toxic in contact with skin) according to CLP.