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Description of key information

An oral LD50 of 396 mg/kg in rat was determined the Hoechst AG (1973). This value was supported by RTECS (1980) and Zeller (1972).
For the application of 2-chlorobenzonitrile in propylene glycole, a dermal LD50 between 340 and 600 mg/kg in rabbits was concluded by TNO (1976). However the result wasn't used, due to possible enhencement of the glycole.
TNO (1974) reported no acute toxicity by inhalation (4h) at the maximum achievable concentration. This result was confirmed by Zeller (1972).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Doses:
125, 200, 320, 500 and 800 mg/kg bw
No. of animals per sex per dose:
10 f
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
396 mg/kg bw
Based on:
test mat.
95% CL:
>= 321 - <= 488
Clinical signs:
jerkingly breathing, vestibular disorder, lateral or abdominal position

Dose [mg/kg bw]

Concentration [%]

Dead animals per dose group

125

1

0 of 10 rats

200

4

1 of 10 rats

320

4

3 of 10 rats

500

4

6 of 10 rats

800

4

10 of 10 rats

 

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of o-Chlorobenzonitrile administered to female rats is 396 mg/kg bw.
Executive summary:

2-chlorobenzonitrile was administered by gavage in a single dose of 125, 200, 320, 500 and 800 mg/kg to 10 female rats per dose. Animals were observed for 14 consecutive days. Mortality occurred in the test groups receiving >= 200 mg/kg bw.

The LD50 was calculated to be 396 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
396 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: SPF albino
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: propylene glycol
Analytical verification of test atmosphere concentrations:
no
Remarks:
The highest concentration being possible in air was calculated from the results of weighings of the solution, converted to pure, undissolved sample material.
Duration of exposure:
4 h
Concentrations:
440 mg/m³ (highest concentration possible)
No. of animals per sex per dose:
five animals per sex (only one dose)
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 440 mg/m³ air
Exp. duration:
4 h
Interpretation of results:
GHS criteria not met
Conclusions:
2-Chlorobenzonitrile presents little acute inhalation hazard.
Executive summary:

The aim of this study was to determine the 4-hour acute inhalation toxicity of 2-Chlorobenzonitrile. Five male and female rats each were exposed (whole body) to the test atmosphere generated by dispersing 2-Chlorobenzonitrile in nine parts propylene glycol to a fine mist by means of an aerodynamic nozzle nebulizer. The mist was passed through a glass exposure cylinder of 15 L capacity at a rate of 1.5 m³/h. The rats were exposed to the highest concentration of 2-Chlorobenzonitrile possible, being 440 mg/m³.

Clinical signs were recorded during exposure and daily thereafter for 14 days. At termination of the study, all surviving animals were subjected to gross necropsy.

Neither mortality nor injury was observed in any of the rats. After the 14 day observation period, at autopsy macroscopical examination did not reveal any deleterious effects.

From the results of the present acute inhalation toxicity test with rats it appeared that a 4 hour exposure to a fine dispersion of 2-Chlorobenzonitrile at a concentration of 440 mg/m³ of air produced no mortality or grossly visible injury. As it is unlikely that the substance will occur at higher concentrations in practice, this results indicates that the product presents little acut inhalation hazard.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

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

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

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").

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

2-chlorobenzonitrile was administered by gavage in a single dose of 125, 200, 320, 500 and 800 mg/kg to 10 female rats per dose (Hoechst, 1973). Animals were observed for 14 consecutive days. Mortality occurred in the test groups receiving >= 200 mg/kg bw. The LD50 was calculated to be 396 mg/kg bw.

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. The dermal LD50 of 2-Chlorobenzonitrile in propylene glycol 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").

No mortality was observed in rats when exposed to a fine dispersion of 2-chlorobenzonitrile (440 mg/m3) for 4h (TNO, 1974).

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 the classification Acute Tox. 4 is warranted based on an oral LD50 of 396 mg/kg bw.

For the dermal route the classification Acute Tox. 4 is warranted because enhencement of glycol was considered in the given test.

There is no acute toxicity reported for the inhalatory route up the maximum achievable concentration of 440 mg/m³ bw.