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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-02-11 - 1997-03-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
4-bromobenzonitrile
EC Number:
210-764-9
EC Name:
4-bromobenzonitrile
Cas Number:
623-00-7
Molecular formula:
C7H4BrN
IUPAC Name:
4-bromobenzonitrile
impurity 1
Chemical structure
Reference substance name:
2-bromobenzonitrile
EC Number:
218-045-1
EC Name:
2-bromobenzonitrile
Cas Number:
2042-37-7
Molecular formula:
C7H4BrN
IUPAC Name:
2-bromobenzonitrile
impurity 2
Chemical structure
Reference substance name:
3-bromobenzonitrile
EC Number:
230-127-9
EC Name:
3-bromobenzonitrile
Cas Number:
6952-59-6
Molecular formula:
C7H4BrN
IUPAC Name:
3-bromobenzonitrile
impurity 3
Chemical structure
Reference substance name:
Benzonitrile
EC Number:
202-855-7
EC Name:
Benzonitrile
Cas Number:
100-47-0
Molecular formula:
C7H5N
IUPAC Name:
benzonitrile
impurity 4
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Water
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, GER
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx 6 w
- Weight at study initiation: within +/- 20 % of the sex mean
- Fasting period before study: over night prior to dosing until 3 - 4 h after adminstration
- Housing: 3 animals per sex per cage, polycarbonate cages, purified sawdust
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 50 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1 % Aq.
Doses:
200 mg/kg BW (m+f)
2000 mg/kg BW (m)
No. of animals per sex per dose:
3
Control animals:
no

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw: 1 m dead on day 2
1 m killed in extremis on day 4
Clinical signs:
200 mg/kg bw: Hunched posture, uncoordinated movements
2000 mg/kg bw: Lethargy, ventro-lateral recumbency, hunched posture, uncoordinated movements, piloerection, swelling of the abdomen, pale skin, red staining of the periorbital region, ptosis of an eye.
Surviving animals have recovered from the symptoms by day 2 (200 mg/kg bw) or by day 14 (2000 mg/kg bw).
Body weight:
Surviving male dosed at 2000 mg/kg bw showed reduced bw gain over the first week, which improved over the 2nd week. The bw gain shown by the other survivig animals over the study period was considered to be similar to that expected of normal untreated anmals of the same age and strain.
Gross pathology:
Enlarged adrenal glands, with hemorrhages, and thymis reduced in size were found in the male that was killed in extremis during the study.
Macroscopic post mortem examination of the other animal that died during the study and of the surviving animals at termination did not reval any abnormalities that are not occasionally noted among rats of this age and strain or were considered toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of 4-Bromobenzonitrile in Wistar rats was established to be within the range of 200-2000 mg/kg bw.
According to GHS criteria 4-Bromobenzonitrile must be classified as hamful and requires the hazardous statement H302 "Harmful if swallowed".
Executive summary:

Assessment of the acute oral toxicity with 4 -Bromobenzonitrile in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute toxic Class Method" and OECD No. 423

"Acute Oral Toxicity - Acute toxic Class Method"

Initially, 4 -Bromobenzonitrile was adminstered by oral gavage th three m Wistar rats at 200 mg/kg bw. In a stepwise procedure additional groups of animals were dosed at 200 (f) and 2000 (m) mg/kg bw. All animals were subjected to daily observations ans weekly determination of bw. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 15).

At a dose level of 2000 mg/kg bw one male was found dead on day 2 and another male was killed in extremis on day 4.

Clincal singns observed during the study period were as follows:

200 mg/kg bw: Hunched posture, uncoordinated movements

2000 mg/kg bw: Lethargy, ventro-lateral recumbency, hunched posture, uncoordinated movements, piloerection, swelling of the abdomen, pale skin, red staining of the periorbital region, ptosis of an eye.

Surviving animals have recovered from the symptoms by day 2 (200 mg/kg bw) or by day 14 (2000 mg/kg bw).

Surviving male dosed at 2000 mg/kg bw showed reduced bw gain over the first week, which improved over the 2nd week. The bw gain shown by the other survivig animals over the study period was considered to be similar to that expected of normal untreated anmals of the same age and strain.

Enlarged adrenal glands, with hemorrhages, and thymis reduced in size were found in the male that was killed in extremis during the study.

Macroscopic post mortem examination of the other animal that died during the study and of the surviving animals at termination did not reval any abnormalities that are not occasionally noted among rats of this age and strain or were considered toxicologically significant.

The oral LD50 value of 4-Bromobenzonitrile in Wistar rats was established to be within the range of 200-2000 mg/kg bw.

According to GHS criteria 4-Bromobenzonitrile must be classified as hamful and requires the hazard statement H302 "Harmful if swallowed".

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