2-chlorobenzonitrile

Acute Toxicity: dermal

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

Test material information

Constituent 1

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:

other: 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 pupi

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").