Registration Dossier

Administrative data

Description of key information

Acute oral Toxicity: 

In Acute oral toxicity,LD50 value for target substance diphenylacetonitrile (CAS no 86-29-3) was considered to be 5000 mg/kg bw (cut-off value) and 3500 mg/kg bw.All the studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, diphenylacetonitrile (CAS no 86-29-3) cannot be classified for acute oral toxicity.

Acute inhalation toxicity: 

The study does not needs to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size (exposure considerations).

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value for target substance diphenylacetonitrile (CAS no 86-29-3) was considered to be >2000 mg/kg bw.The study concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, diphenylacetonitrile (CAS no 86-29-3) cannot be classified for acute dermal toxicity.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Test Item: Diphenyl acetonitrile (CAS No. 86-29-3)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: 0001
- Manufacturing Date: May; 2016
- Expiration date of the lot/batch: November; 2022
- Purity test date: No data
- Consistency: Solid, powder

RADIOLABELLING INFORMATION (not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item and prepared formulation(s) were stored at ambient temperature.
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in 0.5% aqueous Carboxy Methyl Cellulose. The formulation was prepared fresh on the day of dosing.
- Preliminary purification step (if any): No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid:No data available

FORM AS APPLIED IN THE TEST (if different from that of starting material) : No data available

OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 194.2 to 203.8 grams.
Body weights at the start :
Female
Mean : 198.84 g (= 100 %)
Minimum : 194.2 g (- 2.33 %)
Maximum : 203.8 g (+ 2.49 %)
Total No. of animals : 12
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.1 degree centigrade.
- Humidity (%): 56.6% to 61.1%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 10-07-2017 to 29-07-2017
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% aqueous
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle:
1) One of the recommended vehicle for the test.
2) Test item was insoluble in water. Uniformly dispersed suspension of the test item was possible in 0.5% Aqueous Carboxy Methyl Cellulose.
3) Extremely safe with LD50 = 27000 mg/kg body weight.
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data available
Doses:
Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
Dose Group II : 2000 mg/kg

No. of animals per sex per dose:
Three females were used at each step.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Body weights:
Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.

Gross Pathology:
Necropsy was performed on all animals at the end of the study period on day 15. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique.

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:
No data
Preliminary study:
no data
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight. All animals survived through the study period of 14 days.

Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.

Group II
Step I :
Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Group II
Step II :
Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Clinical signs:
Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Group II
Step I :
Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Group II
Step II :
Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Body weight:
Group I
Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 10.13% and 18.92% respectively.

Group I
Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.23% and 17.70% respectively.

Group II
Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.15% and 17.43% respectively.

Group II
Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.96% and 15.21% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
No data available

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Female

Group I :   

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

300

No clinical signs observed

3

1,2,3

Day 0 - Day 14

0/3

 

Group I :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

300

No clinical signs observed

3

4,5,6

Day 0 - Day 14

0/3

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

2000

No clinical signs observed

3

7,8,9

Day 0 - Day 14

0/3

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

2000

No clinical signs observed

3

10,11,

12

Day 0 - Day 14

0/3

 

 

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

300

Mean

197.17

217.17

10.13

234.50

7.98

18.92

± SD

3.42

6.85

1.63

7.28

0.22

1.66

 

 

Group I :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

300

Mean

198.47

214.83

8.23

233.63

8.74

17.70

± SD

3.32

6.50

1.85

8.27

0.85

2.32

 

 

Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

197.93

216.07

9.15

232.47

7.58

17.43

± SD

3.31

5.72

1.26

6.85

0.41

1.60

 

 

Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

2000

Mean

201.80

215.87

6.96

232.53

7.70

15.21

± SD

2.05

5.68

1.73

8.62

1.17

3.10

 

 

Table No.III

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Female

Group I :

 

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

300

1 - 3

TS

No abnormality detected

 

Group I :

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

300

4 - 6

TS

No abnormality detected

 

 Group II :

Step No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

7 - 9

TS

No abnormality detected

 

  

Group II :

Step No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

2000

10 - 12

TS

No abnormality detected

                     

TS = Terminal Sacrifice

Interpretation of results:
other: not classified
Conclusions:
The lethal concentration (LD50-Cut-off value) value for acute oral toxicity test was considered to be 5000 mg/kg bw,when female Sprague Dawley rats were treated with Diphenyl acetonitrile (CAS No. 86-29-3) orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).
Executive summary:

The acute oral toxicity profile of Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.Hence, The lethal concentration (LD50-Cut-off value) value for acute oral toxicity test was considered to be 5000 mg/kg bw,when female Sprague Dawley rats were treated with Diphenyl acetonitrile (CAS No. 86-29-3) orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Data is Kimicsh 1 and from experimental study report

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Quality of whole database:
Waiver

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity study of Diphenyl acetonitrile (CAS No. 86-29-3) was performed in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Test Item: Diphenyl acetonitrile (CAS No. 86-29-3)
- Source of test material: Sustainability Support Services (Europe) AB
- Batch No.of test material: 0001
- Manufacturing Date: May; 2016
- Expiration date of the lot/batch: November; 2022
- Purity test date: No data available
- Consistency: Solid, powder

RADIOLABELLING INFORMATION (Not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient Temperature
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was grounded to fine powder prior to application. The particulates were moistened
with distilled water before application.
- Preliminary purification step (if any):No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available

FORM AS APPLIED IN THE TEST: Paste

OTHER SPECIFICS:
Safety Precautions : Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 221.6 to 253.6 grams at initiation of dosing.
Body weights at the start :
Male
Mean : 249.82 g (= 100 %)
Minimum : 243.1 g (- 2.69 %)
Maximum : 253.6 g (+ 1.51 %)
Total No. of animals : 5
Female
Mean : 225.64 g (= 100 %)
Minimum : 221.6 g (- 1.79 %)
Maximum : 228.8 g (+ 1.40 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.5 degree centigrade.
- Humidity (%): 53.2% to 58.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 22-05-2017 to 04-08-2017
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
(Distilled water)
Details on dermal exposure:
TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No data available
- For solids, paste formed: Yes

VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Duration of exposure:
24 hours
Doses:
A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
No. of animals per sex per dose:
10 (5/sex).
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction:
Dermal reaction was observed daily for study period of 14 days.

Body weights:
Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.


Statistics:
No data
Preliminary study:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Clinical signs:
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Body weight:
Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.27% and 18.53% respectively.

Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.80% and 10.55% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
Other findings:
- Other observations:
Evaluation of Dermal Reaction
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.


Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Male

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

5

1 - 5

Day 0 - Day 14

0/5

 

Sex : Female

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

5

6 - 10

Day 0 - Day 14

0/5

 

  

Table No. II

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Male 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

1 - 5

Day 0 - Day 14

0/5

 

Sex : Female

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

6 - 10

Day 0 - Day 14

0/5

 

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Male

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

249.82

272.98

9.27

296.10

8.48

18.53

± SD

4.13

7.21

2.44

6.16

1.02

2.18

 

Sex : Female

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

225.64

236.50

4.80

249.46

5.49

10.55

± SD

3.02

6.99

1.97

6.14

0.62

1.69

 

Table No.IV

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Male

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

1 - 5

TS

No abnormality detected

 

Sex : Female

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

6 - 10

TS

No abnormality detected

        

TS = Terminal Sacrifice

 

Interpretation of results:
other: Not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with Diphenyl acetonitrile (CAS No. 86-29-3) by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).
Executive summary:

The acute dermal toxicity profile of Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity).

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.Animals exhibited normal body weight gain through the study period of 14 days.Gross pathological examination did not reveal any abnormalities attributable to the treatment.Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with Diphenyl acetonitrile (CAS No. 86-29-3)  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Endpoint conclusion
Endpoint conclusion:
no study available
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Kimicsh 1 and from experimental study report

Additional information

Acute Oral Toxicity: 

In different studies, diphenylacetonitrile (CAS no 86-29-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experimental data in rodents, i.e. most commonly in rats for diphenylacetonitrile (CAS no 86-29-3). The studies are summarized as below –

The experimental study mentioned in study report (2017) for the target chemical diphenylacetonitrile (CAS no 86-29-3)was designed and conducted for acute oral toxicity.The acute oral toxicity profile of Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.Hence, The lethal concentration (LD50-Cut-off value) value for acute oral toxicity test was considered to be 5000 mg/kg bw,when female Sprague Dawley rats were treated with Diphenyl acetonitrile (CAS No. 86-29-3) orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The above study is supported by another experimental study mentioned in handbook (1965) for the Diphenyl acetonitrile (CAS No. 86-29-3).Acute oral toxicity study was performed in rats using Diphenylacetonitrile(86-29-3) .50% mortality was observed at dose 3500 mg/kg bw.Hence,LD50 value was considered to be 3500 mg/kg bw,when rats were treated with Diphenylacetonitrile(86-29-3) orally.

Thus, based on the above summarised studies on target diphenylacetonitrile(CAS no 86-29-3), it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, diphenylacetonitrile(CAS no 86-29-3) cannot be classified for acute oral toxicity.

Acute inhalation toxicity: 

The study does not needs to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size (exposure considerations).

Acute Dermal Toxicity:

In different experimental studies diphenylacetonitrile(CAS no 86-29-3) have been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and rabbits for diphenylacetonitrile(CAS no 86-29-3). The studies are summarized as below -

The experimental study mentioned in study report (2017) for the target chemicaldiphenylacetonitrile (CAS no 86-29-3)was designed and conducted for acute dermal toxicity.The acute dermal toxicity profile of Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity). The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.Animals exhibited normal body weight gain through the study period of 14 days.Gross pathological examination did not reveal any abnormalities attributable to the treatment.Hence, The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with Diphenyl acetonitrile (CAS No. 86-29-3)  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above summarised studies on Diphenyl acetonitrile (CAS No. 86-29-3), it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Diphenyl acetonitrile (CAS No. 86-29-3)cannot be classified for acute dermal toxicity

Justification for classification or non-classification

Based on the above experimental studies on Diphenyl acetonitrile (CAS No. 86-29-3), it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity.Thus, comparing this value with the criteria of CLP regulation, Diphenyl acetonitrile (CAS No. 86-29-3)cannot be classified for acute oral and dermal toxicity.For Acute inhalation toxicity wavier was added so, not possible to classify.