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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chlorobenzonitrile
EC Number:
212-836-5
EC Name:
2-chlorobenzonitrile
Cas Number:
873-32-5
Molecular formula:
C7H4ClN
IUPAC Name:
2-chlorobenzonitrile
impurity 1
Reference substance name:
unknown
IUPAC Name:
unknown
Test material form:
solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
initial weight: 2.23 - 3.06 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
- The test material was dissoved in propylene glycol
- 9 ml of test dissolved test material contain the applied dose
- Half of the animals received the material on the intact skin, the other half on the abraded skin
- Occlusive conditions: treated area was covered with a thin layer of cellulose sheet and wrapped in polyethylene foil
- After exposure for 24 h the test material was removed with water and the animals were wrapped dry
Duration of exposure:
24 hours
Doses:
0, 0.19, 0.34, or 0.6 g/kg body weight
No. of animals per sex per dose:
2 (Half of the animals received the material on the intact skin, the other half on the abraded skin).
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology (liver, kidney, spleen, stomach, treated and untreated skin), other: blood composition

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 340 - <= 600 mg/kg bw
Mortality:
4 (all) animals in the highest dose group (600 mg/kg, during the first days of the observation period); 0 in the 340 mg/kg group, 1 in the 190 mg/kg group (sufferd from diarrhoea and died during the second week)
Clinical signs:
During or at the end of the 24-hour exposure period no abnormalities of the treated skin could be observed in any of the test groups. However, all test rabbits were more or less apathetic. In addition the animals of the highest dose group had widened pupils, showed tremors over the entire body and signs of paresis or paraIysis.
At the end of the observation period none of the remaining rabbits showed any abnormalities that could be attributed to treatment.
Body weight:
Growth and food- and water intake were not adversely affected by the test compound.
Gross pathology:
Gross and microscopical examination revealed haemorrhagic erosions in the stomach and massive centrolobular liver necrosis in animals of the 0.6 g/kg dose group. Damage of the liver and stomach was obserevd after treatment with 0.6 g/kg body weight. There were no distinct differences in reactions either between rabbits treated on the intact or abraded skin or between male and female rabbits.
Other findings:
- Haemoglobin content of the blood and red blood cell counts of rabbits of the 0.34 g/kg dose group were slightly higher than those of control rabbits. Those differences are not considered to be of toxicological significance since values are within the normal range.
- At autopsy, groes examination of the rabbits of the highest dose group, which died during the experiment, revealed haemorrhagic erosions in the stomach of three rabbits. The animal of the lowest dose group that died and the rabbits that survived the experiment did not show macroscopic changes attributable to treatment.
- microscopical examination revealed treatment-related changes in the liver and stomach. Two rabbits of the highest dose group showed massive centrilobular liver necrosis, while small foci of centrilobular liver necrosis were observed in one rabbit of each test group. It is not clear whether these liver injuries are the result of a direct toxic action of the test compound or of an indirect effect resulting from anoxia.
- Three rabbits of the highest doce group showed haemorrhagic erosions in the fundic part of the stomach, which was considered to be due to preterminal conditional decline.
- Other abnormalities in liver, kidneys, heart and the treated skin occurred to about the sarme degree and frequency in test and control animals or occurred in a single rabbit and are, therefore, not considered te be of toxicological significance.

Any other information on results incl. tables

Table – individual body weight

number

sex

Dose (mg/kg)

Condition of skin

Body weight day 0 (kg)

Body weight end of week 1 (kg)

Body weight end of week 2 (kg)

3638

M

0

abraded

3.06

3.09

3.36

3639

M

0

intact

2.60

2.55

2.78

3627

F

0

abraded

2.93

2.88

3.13

3625

F

0

intact

2.93

2.30

2.45

3641

M

190

abraded

3.05

3.07

3.32

3644

M

190

intact

2.45

2.43

2.82

3662

F

190

abraded

2.55

1.77

dead

3663

F

190

intact

2.70

2.68

3.00

3645

M

340

abraded

2.65

2.83

2.82

3646

M

340

Intact

3.05

3.00

3.36

3660

F

340

abraded

2.62

2.85

3.15

3661

F

340

intact

2.32

2.50

3.02

3635

M

600

abraded

3.05

dead

dead

3637

M

600

intact

2.61

dead

dead

3621

F

600

abraded

2.88

dead

dead

3622

F

600

intact

2.36

dead

dead

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of 2-Chlorobenzonitrile is between 340 and 600 mg/kg bw in rabbits under conditions of this study.
It should be noted that resorption of the test substance has probably been enhanced due to the application in propylene glycol. Therefore, 2-Chlorobenzonitrile is not classified as H311 ("Toxic in contact with skin") but H312 ("Harmful in contact with skin").
Executive summary:

The acute dermal toxicity of 2-Chlorobenzonitrile was examined in an experiment with 8 adult New Zealand White Rabbits/sex/dose. The animals were treated with 2-Chlorobenzonitrile dissolved in propylene glycol at dose levels of 0, 0.19, 0.34 or 0.6 g/kg body weight for 24h. Half the number of animals received the material on the intact skin, the other half on abraded skin.

The dermal application caused apathy of the rabbits in all test groups and widened pupils, tremors and paresis or paralysis in the highest dose group. All animals of the highest dose group died during the first days. The animals of the other groups recovered completely, except one rabbit of the 0.19 g/kg dose group that suffered from diarrhoea and died during the second week of the observatiuon period.

The dermal LD50 of 2 -Chlorobenzonitrile was concluded to be between 340 and 600 mg/kg bw.

It should be noted that resorption of the test substance has probably been enhanced due to the application in propylene glycol. Therefore, 2-Chlorobenzonitrile is not classified as H311 ("Toxic in contact with skin") but H312 ("Harmful in contact with skin").

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