Registration Dossier

Administrative data

Description of key information

Several acute toxicity studies are available for all routes. Overall with sufficient reliability. 

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:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Charles River Albino (COBS)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
ranging from 0.6 to 2.0 g/kg bw
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Mortality:
see "Other results incl Tables"

The acute oral median lethal dose (LD50) was calculated using the techniques of Weil (1952), Thompson (1947), and Thompson and Weil (1952).

 

Acute Oral Toxicity Study with Albino Rates – Mortality and Body Weight Data

 

Dose*
(g/kg)

Animal Number and Sex

Individual Body Weights (grams) Test Day Number

Number Dead / Number Tested

Percent Dead

0

14

0.6

1-M

252

342

0/4

0

2-M

242

326

3-F

183

234

4-F

180

230

0.9

5-M

233

346

2/4

50

6-M

220

(2 days)

7-F

196

(3 days)

8-F

178

243

1.4

9-M

176

283

3/4

75

10-M

249

(6 days)

11-F

194

(2 days)

12-F

197

(2 days)

2.0

13-M

214

(3 days)

4/4

100

14-M

221

(3 days)

15-F

220

(3 days)

16-F

184

(6-22 hours)

Note: Figures in parentheses indicate time of death

* Benzonitrile ws administered undiluted.

Acute Oral LD50 = 1.0 g/kg

Standard Deviation of LD50 =±.2 g/kg

Summary of Reactions to the Acute Oral Toxicity Study of Albino Rats

Dose
(g/kg)

Reaction

Time of Onset following Dose Administration (hours)

Duration of Reaction (days)

Time of Death Following Dose Administration (days)

0.6

Hyperactivity

6-22

2

-

Muscular weakness

6-22

2

Ruffed fur

6-22

2

0.9

Hyperactivity

1

3

2-3

Muscular weakness

1

3

Ruffed fur

6-22

2

Prostration

6-22

2

1.4

Hyperactivity

1

4

2-6

Muscular weakness

1

4

Ruffed fur

6-22

4

Prostration

6-22

2

2.0

Hyperactivity

1

Until death

6 hours3 days

Muscular weakness

1

 

Ruffed fur

6-22

 

Prostration

6-22

 

Dyspnea

6-22

 

Lacrimation

1 day

 

 

 

Interpretation of results:
Toxicity Category IV
Conclusions:
The acute oral median lethal dose (LD50) for oral application of benzonitrile on rats was determined at: LD50= 1.0 g/kg.

Executive summary:

In an acute oral toxicity study 4 groups (2 male + 2 female each) of young Albino rats (body weight ranged from 176 to 252 grams) were given a single oral dose of undiluted benzonitrile at doses of 0.6, 0.9, 1.4 and 2.0 g/kg bw.  Animals were then observed for 14 days.

Oral LD50 Combined = 1.0 g/kg  bw (Standard Deviation of LD50 =±0.2 g/kg)

Benzonitrile is of slight toxicity based on the combined LD50. According (EC) 1272/2008 benzonitrile is classified as acute toxic Category 4.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 000 mg/kg bw
Quality of whole database:
good; none of the available studies indicate a more severe oral toxicity.

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:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
male/female
Details on test animals and environmental conditions:
Young adult albino rats with average body weight of 220 g were used as test animals.
The rats were housed individually in stock cages and maintained on a standard laboratory diet of Purina Rat Chow plus water ad libitum, except during inhalation exposure.
Each exposure of individual rat in specially constructed all-Plexiglass inhalation chamber (with a capacity of 70 L) ran for 240 min (4 h) during which time observations were made.
At the end of the exposure the rats were returned to their stock cages and observed for the following 14 days.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
Undiluted test material was passed through Ohio Ball-Jet Nebulizer using clean dry air (-40°C dew point), resulting air-aerosol stream mixed with clean dry air to desired aerosol concentration, introduced into the exposure chamber from the top (exhausted from the bottom).
Average aerosol concentrations were calculated by dividing the nebulizer weight loss by the total volume of air used during each inhalation exposure (see "any other information materials and methods").
Duration of exposure:
240 min
Concentrations:
0.8 mg/L and 8.0 mg/L air average aerosol concentration of undiluted benzonitrile
No. of animals per sex per dose:
5
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.8 mg/L air
Exp. duration:
4 h
Remarks on result:
other: no effect
Key result
Sex:
male/female
Dose descriptor:
LCLo
Effect level:
8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 3 of 10 dead
Interpretation of results:
GHS criteria not met
Conclusions:
The acute aerosol inhalation study performed on rats provided no effects at the low dose of 0.8 mg/L air and 3 out of 10 death at the high dose of 8.0 mg/L air.
Executive summary:

In an acute inhalation toxicity study, two groups of young adult Charles River albino rats (5 male + 5 female) were exposed by inhalation route to undiluted benzonitrile aerosol in a specially constructed all-Plexiglass inhalation chamber (with a capacity of 70 L). The exposure ran for 240 min (4 h) at concentrations of 0.8 mg/L and 8.0 mg/L. Animals then were observed for 14 days.

No effects were observed at low concentration. At 8 mg/L the mortality was 3 out of 10 (LD50 > 8 mg/L).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
8 000 mg/m³
Quality of whole database:
ambigous results. LC50 in rat range form 3.9 to 38.6 mg/L. Mice seem to be more sensitive with LD50 values in the range of 1.8 - 6 mg/L.

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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
other: 40 CFR Part 163.81-2
Principles of method if other than guideline:
EPA, Pesticides Programs, proposed guidelines for registering pesticides in the U.S., hazard evaluation: humans and domestic animals
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
2.0 g/kg, and thereafter 0.01, 0.05, 0.1, 0.5, and 1.0 g/kg,
No. of animals per sex per dose:
1 male + 1 female for range finding and 4 male + 4 female for LD50 determination

Control animals:
yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
95% CL:
1 - 1.8

Preliminary Range Finding Study:

Dose

Mortality

(g/kg)

 

0.01

0/2

0.05

0/2

0.1

0/2

0.5

0/2

1.0

0/2

 

Dose level, mortality data and LD50calculations:

 

Dose Level

Mortality

 

(g/kg)

Male

Female

Abraded Skin

Intact Skin

Total

Mortality

0.5

0/4

0/4

0/4

0/4

0/8

0.7

0/4

1/4

0/4

1/4

1/8

1.0

0/4

2/4

1/4

1/4

2/8

1.4

1/4

3/4

1/4

3/4

4/8

2.0

3/5

5/5

8/10

0/0

8/10

Control

(0/4)

(0/4)

(0/4)

(0/4)

(0/4)

LD50

 

1.8

1.0

1.55

1.05

1.4

95% Confidence Limit

 

1.2 to
2.4

0.6 to
1.4

1.15 to
1.95

0.65 to
1.45

1.0 to
1.8

 

Interpretation of results:
Toxicity Category IV
Conclusions:
The LD50 was calculated at 1.4 g/kg.
Executive summary:

In an acute dermal toxicity study, groups of 4 young adults New Zealand White rabbits/sex/dose were dermally exposed to Benzonitril (100 % a.i) for 24 hours to 10% of body surface area at doses of 0.5, 0.7, 1.0, 1.4 and 2.0 g/kg bw. Animals then were observed for 14 days.

 

Dermal LD50:

      Males =1.8 g/kg bw (95% C.I. 1.2 to 2.4 g/kg bw)

      Females = 1.0 g/kg bw (95% C.I. 0.6 to 1.4 g/kg bw.)

      Combined = 1.4 g/kg bw (95% C.I. 1.0 to 1.8 g/kg bw.)

  

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 400 mg/kg bw
Quality of whole database:
good; none of the available studies indicate a more severe dermal toxicity.

Additional information

Several acute toxicity studies report oral LD50 values between 690 - 1500 mg/kg in rat; up to 1400 mg/kg in mouse; 800 mg/kg in rabbit and 400-800 mg/kg in cat. The oral LD50 in rats is 800 mg/kg bw. For chemical safety assessement an LD50 of 1000 mg/kg (rat) is taken from Mastri et al. (1970).

Several acute toxicity studies are available for the inhalation route. No mortalities were reported after 4h exposure to saturated vapour (Zeller, 1969); an LC50 of above 8 mg/L was reported by Mastri (1970) and Cato (1974). LC50 in mouse range from 2.95 mg/L (MacEwen, 1974) to 6 mg/L (Agaev, 1975). Most reports do not present sufficient data to evaluate the method used for generation an exposure atmosphere. The most reliable description is presented by Mastri et al. (1970). The LC50 of > 8 mg/L (aerosol/mist) reported in this study does not lead to a classification according regulation (EC) 1272/2008. Mice seam more sensitive, but aren't the typical species used for classification. Therefore only results for rat are used for classification.

LD50 values form acute dermal toxicity studies were reported to be 1400 mg/kg (Auletta, 1980), 1200 mg/kg (Mastri, 1970), and 1250 mg/kg (Moreno, 1977). Zeller 1969 report an LD100 of 1500 mg/kg in rabbit and an LD0 or 200 mg/kg. Auletta (1980) was conducted according an US-EPA method and is considered the most reliable study. An LD50 of 1400 mg/kg is used for chemical safety assessment.


Justification for selection of acute toxicity – oral endpoint
most reliable study; similar to OECD 401

Justification for selection of acute toxicity – inhalation endpoint
most reliable study; similar to OECD 403

Justification for selection of acute toxicity – dermal endpoint
most reliable guideline study

Justification for classification or non-classification

Benzonitrile is classified Acute Tox. 4 with respect to oral (LD50 = 1000) and dermal (LD50 = 1400 mg/kg) exposure according to regulation (EC) 1272/2008. For the inhalation route a classification is not warranted based on an LC50 > 8 mg/L (aerosol/mist) with rat.