Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity,LD50 value for target substance was considered to be > 200<= 2000 mg/kg of body weight (MLD value),500 mg/kg bw,1050 mg/kg bw in male rats and 930 mg/kg bw in female rats,1126 mg/kg bw,1600 mg/kg bw and 1200 mg/kg bw in rats;1070 mg/kg bw,540 mg/kg bw and 900 mg/kg bw in mouse;1700 mg/kg bw in rabbits.All these studies concluded that the LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, test chemical can be classified as “Category IV” for acute oral toxicity.

 

Acute Inhalation Toxicity: 

test chemical has very low vapor pressure, so the potential for the generation of inhalable forms is low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and therefore no inhalation test was performed and therefore the acute inhalation toxicity end point was considered for waiver.

 

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value for target substance  was considered to be >2000 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, 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
Study period:
August 1989-September 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from experimental report
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Acute Oral toxicity test was carried out to study the effects of test chemical on 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:
no data available
Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
no data available
Doses:
200,2000 mg/kg bw
No. of animals per sex per dose:
3 male/female (200 mg/kg)
3 male(2000 mg/kg)
Control animals:
not specified
Details on study design:
no data available
Statistics:
no data available
Preliminary study:
no data available
Sex:
male/female
Dose descriptor:
other: MLD
Effect level:
200 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
other: MLD
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: mortality was observed
Mortality:
all male rats died at dose 2000 mg/kg bw
Clinical signs:
no data available
Body weight:
no data available
Gross pathology:
no data available
Other findings:
no data available

 

 

Number of treated animals

Number of animals died

 

 

Female

Male

Female

Male

1

Test dose: 2000 mg

Test step 1

Test step 2

 

-

-

 

3

-

 

-

-

 

3

-

2

Test dose: 200 mg

Test step 1

Test step 2

 

-

3

 

3

-

 

-

0

 

0

-

Interpretation of results:
Toxicity Category IV
Conclusions:
The mean lethal dose (MLD) of test chemical in male and female wistar rat was considered to be > 200<= 2000 mg/kg of body weight. Acute oral toxicity of test chemical to rat by oral route indicates that test chemical exhibits acute toxicity by the oral route in the Category 4.
Executive summary:

The mean lethal dose (MLD) of test chemical in male and female wistar rat was considered to be > 200<= 2000 mg/kg of body weight. Acute oral toxicity of test chemical to rat by oral route indicates that test chemical exhibits acute toxicity by the oral route in the Category 4.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and from 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:
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from study report
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity test was carried out to study the effects of test chemical on rats.
GLP compliance:
no
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
- Age at study initiation: Healthy young adult were used.Females were nulliparous and non pregnant.
- Weight at study initiation: Male: Minimum: 218 g and Maximum: 261 g
(Prior to Treatment) Female:Minimum: 210 g and Maximum: 221 g

- Fasting period before study: no data
- Housing:
Bedding : All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 25/2014
Husbandry : The animals were housed individually in polycarbonate cages.
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): animals were provided conventional laboratory rodent diet ad libitum
- Water : Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: All animals were acclimatized to the test conditions for 6 days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.90 °C Maximum: 23.30 °C
- Humidity (%): Minimum: 52.30% Maximum: 66.50%
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: Approx. 10% of body surface area of rat
- Type of wrap if used: porous gauze dressing and non-irritating tape

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 ml
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
total:10 animals
2000 mg/kg bw:male 5 and female:5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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 for clinical signs, teice daily for mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
no data available
Preliminary study:
no data available
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:
All the animals were observed with normal clinical signs throughout the experimental period
Body weight:
In males and females, mean body weight was observed with gain on day 7 and 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

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

222

232

248

4.50

11.71

2

237

243

256

2.53

8.02

3

261

279

314

6.90

20.31

4

255

276

297

8.24

16.47

5

218

229

232

5.05

6.42

6

Female

214

231

244

7.94

14.02

7

212

222

228

4.72

7.55

8

221

237

253

7.24

14.48

9

210

222

241

5.71

14.76

10

213

220

232

3.29

8.92

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

1

Male

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

1

1

1

1

 

Animal

No.

Sex

Day

8

9

10

11

12

13

14

1

Male

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

Key: 1 = Normal

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

Summaryof Animal Body Weight (g) and Body Weight Changes (%)

Dose:2000 mg/kg body weight

Sex

Body Weight (gram)

Body Weight Changes (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

Male

Mean

238.60

251.80

269.40

5.44

12.59

SD

19.19

24.06

34.59

2.20

5.80

n

5

5

5

5

5

Female

Mean

214.00

226.40

239.60

5.78

11.95

SD

4.18

7.30

9.91

1.88

3.43

n

5

5

5

5

5

Keys:SD= Standard deviation, n = Number of animals

GrossNecropsyObservation

 Dose:2000 mg/kg body weight                                               Mode of Death:Terminal Sacrifice

Animal No.

Sex

Gross Observation

External

Internal

1

Male

No abnormality detected

No abnormality detected

2

No abnormality detected

No abnormality detected

3

No abnormality detected

No abnormality detected

4

No abnormality detected

No abnormality detected

5

No abnormality detected

No abnormality detected

6

Female

No abnormality detected

No abnormality detected

7

No abnormality detected

No abnormality detected

8

No abnormality detected

No abnormality detected

9

No abnormality detected

No abnormality detected

10

No abnormality detected

No abnormality detected

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw,when male and female wistar rats were occlusively treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).
Executive summary:

Acute dermal Toxicity Study of test chemical in Rats was performed as per OECD No. 402 (Acute Dermal Toxicity) . Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free 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 directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area.This porous gauze dressing was covered with a non-irritating tape.After the 24-hour application period, the dressings were removed and theskin was gently wiped with distilled water.The skin reactions were assessed. 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. All the animals shows normal clinical signs, mean body weight was observed with gain on day 7 and 14. Gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.Thus, The LD50 value was considered to be >2000 mg/kg bw,when male and female  wistar rats were occlusively treated with test chemical (54-21-7)  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 study report

Additional information

Acute Oral Toxicity: 

In different studies, test chemical 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 test chemical. The studies are summarized as below –

 

In experimental study conducted by Sustainability Support Service (Europe) AB (study number: 10A0263/89 1050, 1989-09-25) for the target substance test chemical.

The mean lethal dose (MLD) of test chemical in male and female wistar rat was considered to be > 200<= 2000 mg/kg of body weight. Acute oral toxicity of sodium salicylate to rat by oral route indicates that test chemical exhibits acute toxicity by the oral route in the Category 4.

 

In another experimental study conducted by Sustainability Support Service (Europe) AB (study number: IIRT-350, 2012-11-23) for the target substance .The acute oral toxicity profile of test chemical in female wistar albino rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).The test substance was dissolved in Distilled water to obtain final concentration of 30 and 200 mg/ml which was administered by oral route by using oral cannula. Body weight, mortality and clinical signs were observed in treated animals at dose level 300 mg/kg bw,Test compound did not produce any clinical signs of intoxication throughout the observation period of 14 days.atdose level 2000 mg/kg bw,Test compound produced high to sever signs of intoxication viz; abdominal respiration, convulsion, tremor and hind leg paralysis and finally death after 4 hrs.All the animals treated with CAS No. 54-21-7 at the dose level of 300 mg/kg bw showed decrease in normal gain in body weight on day 7th as compared to control group. Whereas, on day 14th all the rats showed normal gain weight as compared to control group. Hence, The lethal concentration (LD50) cut-off value for acute oral toxicity test was considered to be 500 mg/kg bw, when female wistar albino rats were treated with test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

 

The study is further supported by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017); IFA GESTIS (Gestis Substance Database ,2018) and RTECS database (RTECS (registry of toxic effect of chemical substance database ), 2018) for the target substance.Acute oral toxicity study was performed in groups of 10 fasted wistar rats using test material.50% mortality was observed at dose 1050 and 930 mg/kg bw. Clinical signs like behavioral muscle contraction or spasticity and convulsions or effect on seizure threshold were observed.Hence,LD50 value was considered to be 930 mg/kg bw in females and 1050 mg/kg bw in males, when groups of 10 fasted wistar rats were treated with test chemical orally.

The above study is further supported by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003) for the target substance test chemical.Acute oral toxicity study was performed in male Fischer 344 rats using test material .50% mortality was observed at dose 1126 mg/kg bw. Hence,LD50 value was considered to be 1126 mg/kg bw,when male Fischer 344 rats were treated with test chemical orally.

 

In another experimental study conducted by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003) and E. ROSS HART (Journal of Pharmacology and Experimental Therapeutics March 1947, 89 (3) 205-209)for the target substance.Acute oral toxicity study was performed in rats using test material.50% mortality was observed at dose 1600 mg/kg bw. Hence, LD50 value was considered to be 1600 mg/kg bw, when rat were treated with test chemical orally.

 

Also the above study is further supported by Richard J. Lewis, Sr. (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012)for the target substance.Acute oral toxicity study was performed in rats using test material.50% mortality was observed at dose 1200 mg/kg bw. Hence, LD50 value was considered to be 1200 mg/kg bw, when rats were treated with test chemical orally.

 

The above study is further supported by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003)for the target substance Acute oral toxicity study was performed in mouse using test material.50% mortality was observed at dose 1070 mg/kg bw. Hence, LD50 value was considered to be 1070 mg/kg bw, when mouse were treated with test chemical orally.

 

Also these results are further supported by the experimental study conducted by Richard J. Lewis, Sr. (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS database (RTECS (registry of toxic effect of chemical substance database ), 2018) for the target substance.Acute oral toxicity study was performed in mouse using test material.50% mortality was observed at dose 540 mg/kg bw. Hence, LD50 value was considered to be 540 mg/kg bw,when mouse were treated with test chemical orally.

 

The study is further supported by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003) and E. ROSS HART (Journal of Pharmacology and Experimental Therapeutics March 1947, 89 (3) 205-209)for the target substance.Acute oral toxicity study was performed in mouse using test material .50% mortality was observed at dose 900 mg/kg bw. Hence, LD50 value was considered to be 900 mg/kg bw,when mouse were treated with test chemical orally.

 

Also these results are further supported by the experimental study conducted by Cosmetics Ingredient Review Expert Panel(International Journal of Toxicology, 22(Suppl. 3):1–108, 2003); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS database (RTECS (registry of toxic effect of chemical substance database ), 2018) for the target substance. Acute oral toxicity study was performed in rabbits using test material .50% mortality was observed at dose 1700 mg/kg bw. Hence, LD50 value was considered to be 1700 mg/kg bw, when rabbit were treated with test chemical orally.

 

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

 

Acute Inhalation Toxicity: 

Test chemical has very low vapor pressure, so the potential for the generation of inhalable forms is low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and therefore no inhalation test was performed and therefore the acute inhalation toxicity end point was considered for waiver.

 

Acute Dermal Toxicity:

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

 

In experimental study conducted by Sustainability Support Services (Europe) AB (study number:14_49_066) for the target substance. Acute dermal Toxicity Study of test chemical in Rats was performed as per OECD No. 402 (Acute Dermal Toxicity) . Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free 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 directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. 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. All the animals shows normal clinical signs, mean body weight was observed with gain on day 7 and 14. Gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Thus, The LD50 value was considered to be >2000 mg/kg bw, when male and female  wistar rats were occlusively treated with test chemical  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

 

The above study was further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 17, Supplement, December 1979, Pages 873-874); HPVIS (HPVIS,2018); IFA GESTIS (Gestis Substance Database ,2018) and U.S. National Library of Medicine(Chemidplus Database,U.S. National Library of Medicine,2017).No mortality was observed in treated rabbits at dose 5000 mg/kg bw.Therefore, LD50 value was considered to be >5000 mg/kg bw,when rabbits were topically treated with test chemical.

 

Also these results are further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and IFA GESTIS (Gestis Substance Database ,2018). In acute dermal toxicity study, rabbits were treated with test chemical in the concentration of 10000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 10000 mg/kg bw. Therefore, LD50 value was considered to be >10000 mg/kg bw, when rats were treated with test chemical by dermal application.  

 

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

Justification for classification or non-classification

Based on the above experimental studies on test chemical it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity and greater than 2000 mg/kg bw for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, 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.