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Administrative data

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on mice for the test chemical. The LD50 value is between 300-2000 mg/kg bw for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified as “Category IV” for acute oral toxicity.

Acute Inhalation Toxicity:

This data was considered for waiver considering the low vapour pressure of this test chemical (0.3853 Pascal) as well as the particle size distribution. Majority of the particles were found to be more than 150 (72.33%) micrometer in size which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the test chemical is highly unlikely.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on experimental study conducted on rats for the test chemical. The studies concluded that LD50 value is >2000 mg/kg bw for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The acute toxicity of the test chemical by oral administration in mice was determined according to Weil (1952), using four animals per dosage level and four different doses.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
mouse
Strain:
other: ddY
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 29 ± 2.2 g body weight
- Housing: Plastic cages containing wooden flakes.
- Diet (e.g. ad libitum): laboratory chow ad libitum
- Water (e.g. ad libitum): water ad libitum
Route of administration:
oral: unspecified
Vehicle:
DMSO
Details on oral exposure:
no data available
Doses:
712.23 - 1233.7 mg/kg bw
No. of animals per sex per dose:
total:4 male mice
Control animals:
not specified
Details on study design:
no data available
Statistics:
The acute toxicity of the test compounds by oral administration in mice was determined according to Weil (1952).
Preliminary study:
no data available
Sex:
male
Dose descriptor:
LD50
Effect level:
941.174 mg/kg bw
Based on:
test mat.
95% CL:
712.23 - 1 233.7
Remarks on result:
other: 50% mortality was observed
Mortality:
50% Mortality was observed in treated mice at 941.174 mg/kg bw
Clinical signs:
no data available
Body weight:
no data available
Gross pathology:
no data available
Other findings:
no data available
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The lethal concentration (LD50) value for acute oral toxicity test was considered to be 914.174 mg/kg bw (95% confidence limit:712.23 - 1233.7 mg/kg),when 4 male ddy strain mice were treated with test chemical orally.
Executive summary:

Acute oral toxicity study was performed in 4 male ddy strain mice using test chemical at dose concentration of 712.23 - 1233.7 mg/kg bw.DMSO was used as vehicle.50% mortality was observed at dose 914.174 mg/kg bw (95% confidence limit:712.23 - 1233.7 mg/kg).Hence,LD50 value was considered to be 914.174 mg/kg bw,when mice were treated with test chemical orally.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
941.174 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from publication

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
The objective of the study was to assess the dermal toxicity of test chemical after single dose application by dermal route in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:In-House Bred at sa-Ford, Animal Facility
- Age at study initiation:N/A
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight (Prior to Treatment):Male: Minimum: 226 g and Maximum: 253 g , Female: Minimum: 233 g and Maximum: 244 g
- Fasting period before study:N/A
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding : All cages were provided with corn cobs.
- Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle : All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.
- Randomization : Animals were selected manually. No computer generated randomization program was used.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 20.40 °C and Maximum: 23.10 °C
- Humidity (%):Minimum: 38.40% and Maximum: 56.00%
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12:12

Type of coverage:
semiocclusive
Vehicle:
other: distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure:The test item was applied uniformly over clipped dorsal area of rat skin.
- % coverage:Approximately 10% body surface area of rats.
- Type of wrap if used:The porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using distilled water.
- Time after start of exposure:24-hour.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A limit dose of 2000 mg/ kg body weight of test item was applied.
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):0.2 ml distilled water
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
10 (Five per sex)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Daily
- Necropsy of survivors performed: yes
At the end of 14 day observation period, all the surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Other examinations performed:
- Clinical signs : After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.

- Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14.

other:
- Local Signs/Skin Reactions
All animals were observed once daily during days 1-14 (in common with clinical signs).

- Mortality
Animals were observed twice daily for any mortality during the experimental period.
Statistics:
No statistical analysis was performed since the study was terminated with limit test.
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:
No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.
Clinical signs:
No systemic or local signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period, except mild erythema from day 2 to 9 and scab from day 10 to 12 was observed in female animal no. 10
Body weight:
There was declined mean body weight gain of male (on day 7) and female animals (on day 7 and 14) was observed as compared to day 0, whereas only male animals were observed with body weight gain on day 14 as compared to day 0.
Gross pathology:
The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.
Other findings:
no data available

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.

Sex

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

Male

253

239

256

-5.53

1.19

2

246

238

276

-3.25

12.20

3

238

227

238

-4.62

0.00

4

226

217

221

-3.98

-2.21

5

247

238

255

-3.64

3.24

6

Female

233

226

227

-3.00

-2.58

7

244

246

247

0.82

1.23

8

242

234

243

-3.31

0.41

9

243

240

229

-1.23

-5.76

10

242

235

244

-2.89

0.83


Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

Animal No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

Male

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

65+

65+

65+

65+

65+

65+

65+

65+

146

146

146

1

1

Keys: 1 = Normal, 65 = Erytema, 146 = Scab, + = Mild


Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

1

Male

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

Female

No mortality and morbidity

No mortality and morbidity

7

No mortality and morbidity

No mortality and morbidity

8

No mortality and morbidity

No mortality and morbidity

9

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity

 

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw,when groups of 5 male and female wistar rats were semiocclusively treated with test chemical 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 test chemical in groups of 5 male and female wistar rats was done according to OECD Guideline 402 (Acute Dermal Toxicity)at dose concentration of 2000 mg/kg bw Distilled water was used as vehicle.Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Ratsfree from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment.On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area.This gauze patch was covered with a non-irritating adhesive tape.The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape.After the 24-hour application period, the dressings were removed and theskin was gently wiped with distilled water.The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.No mortality was observed in any animal till the end of the experimental period.No systemic or local signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period, except mild erythema from day 2 to 9 and scab from day 10 to 12 was observed in female animal no. 10.There was declined mean body weight gain of male (on day 7) and female animals (on day 7 and 14) was observed as compared to day 0, whereas only male animals were observed with body weight gain on day 14 as compared to day 0.The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence,The LD50 value was considered to be >2000 mg/kg bw,when male and female wistar rats were semiocclusively treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and from experimental study report

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in mice for test chemical. The studies are summarized as below –

Acute oral toxicity study was performed in 4 male ddy strain mice using test chemical at dose concentration of 712.23 - 1233.7 mg/kg bw.DMSO was used as vehicle.50% mortality was observed at dose 914.174 mg/kg bw (95% confidence limit:712.23 - 1233.7 mg/kg).Hence,LD50 value was considered to be 914.174 mg/kg bw,when mice were treated with test chemical orally.

The above study is supported with another study mentioned in publication and conducted on mice for the test chemical. Acute oral toxicity study was performed in 4 male ddy strain mice using test chemical at dose concentration of 568.2-1686.3 mg/kg bw.DMSO was used as vehicle.50% mortality was observed at dose1210 mg/kg bw(95% confidence limit:568.2-1686.3 mg/kg bw).Hence,LD50 value was considered to be 1210 mg/kg bw,when mice were treated with test chemical orally.

Both the above studies are further supported with the study mentioned in publication for the test chemical. Acute oral toxicity study was performed in 4 male ddy strain mice using test chemical at dose concentration of 333-672 .33 mg/kg bw.0.9% saline was used as vehicle.50% mortality was observed at dose 477 mg/kg bw(95% confidence limit:333-672.33 mg/kg bw).Hence,LD50 value was considered to be 477 mg/kg bw,when mice were treated with test chemical orally.

Also these results are further supported with another study mentioned in publication for test chemical. Acute oral toxicity study was performed in 4 male ddy strain mice using test chemical at dose concentration of 226.31-599.74 mg/kg bw.0.9% saline was used as vehicle.50% mortality was observed at dose 419 (95% confidence limit: 226.31-599.74 mg/kg bw)).Hence,LD50 value was considered to be 419 mg/kg bw,when mice were treated with test chemical orally.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified as “Category IV” for acute oral toxicity.

 

Acute Inhalation Toxicity:

This data was considered for waiver considering the low vapour pressure of this test chemical (0.3853 Pascal) as well as the particle size distribution. Majority of the particles were found to be more than 150 (72.33%) micrometer in size which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the test chemical is highly unlikely.

 

Acute Dermal Toxicity:

The acute dermal toxicity profile of test chemical in groups of 5 male and female wistar rats was done according to OECD Guideline 402 (Acute Dermal Toxicity) at dose concentration of 2000 mg/kg bw. Distilled water was used as vehicle.Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Ratsfree from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment.On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area.This gauze patch was covered with a non-irritating adhesive tape.The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape.After the 24-hour application period, the dressings were removed and theskin was gently wiped with distilled water.The skin reactions were assessed.The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.No mortality was observed in any animal till the end of the experimental period.No systemic or local signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period, except mild erythema from day 2 to 9 and scab from day 10 to 12 was observed in female animal no. 10.There was declined mean body weight gain of male (on day 7) and female animals (on day 7 and 14) was observed as compared to day 0, whereas only male animals were observed with body weight gain on day 14 as compared to day 0.The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence,The LD50 value was considered to be >2000 mg/kg bw,when male and female wistar rats were semiocclusively treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above summarised study on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.a

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral and >2000 mg/kg bw for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified as “Category IV” for acute oral toxicity and cannot be classified for acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.