Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats, mice and guinea pigs for the given test chemical. The LD50 value is 2000 mg/kg bw. The study concluded that 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 in “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 0.024 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

 

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats and rabbits for the test chemical. The study 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:
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:
According to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd, Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 11 Weeks
- Weight at study initiation: 176.30 to 193.98 g
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Fasting period before study: rats were fasted overnight (16 to 18 hours).
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- Diet (e.g. ad libitum): Hypro Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS, eight days for G2-FTS and ten days for G2-STS before treatment. Animals were observed once daily during acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24°C
- Humidity (%): 66 to 68%
- Air changes (per hr): air conditioned with adequate fresh air supply (12.4 to 13.0 air changes/hour).
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From: 18 April 2018 To: 28 August 2018
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSAGE PREPARATION (if unusual): Undiluted test item as supplied by the sponsor was administered based on the density of the test item i.e., 1.01 g/cm3 at 27°C (as per TIDS) and the
dose volume was 1.98 and 0.30 mL/kg body weight to attain the doses of 2000 and 300 mg/kg body weight as a single oral gavage.
Doses:
G1 (FTS) - 2000 mg/kg
G2 (FTS) - 300 mg/kg
G1 (STS) - 300 mg/kg
No. of animals per sex per dose:
G1 (FTS) - 2000 mg/kg - 3
G2 (FTS) - 300 mg/kg - 3
G1 (STS) - 300 mg/kg - 3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and pre-terminal deaths - At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.
Body weights - The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
- Necropsy of survivors performed: yes, the rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy. Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.
Statistics:
not specified
Preliminary study:
not specified
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg body weight (G1-FTS) one rat died at 4 hours post dose and the other rat was found dead on day 2.
At G2 - [300 mg/kg body weight - Treatment (FTS & STS)]: There was no mortality.
Clinical signs:
G1 - [2000 mg/kg body weight - Treatment (FTS)]: Clinical signs of recumbency and ataxia were observed in two rats at 30 minutes to 4 hours.
G2 - [300 mg/kg body weight - Treatment (FTS & STS)]: There were no clinical signs observed.
Body weight:
G1 - [2000 mg/kg body weight - Treatment (FTS and STS)]: The dead rats had lost body weight and the surviving rat gained bodyweight throughout the observation period.
G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: All the rats gained bodyweight throughout the observation period.
Gross pathology:
There were no gross pathological changes at necropsy.
Other findings:
not specified

TABLE 1.      Body weight, body weight change and pre-terminal deaths

Group and

Dose

(mg/kg

body weight)

Rat

No.

Sex

Body weight (g)

Day of Death

 (Time of Death)

No. dead/

 No. tested

Pre-terminal deaths

(%)

Initial

(Day 1)

8thday

Weight change

(day 8 – Initial)

15thday

Weight change          

(day 15 – Initial)

At Death

G1

(FTS)

2000

 

Rm9115

F

193.98

-

-

-

-

186.75

2 (8.55 AM)

2/3

66.66

Rm9116

F

182.88

-

-

-

-

177.78

1 (2.38 PM)

Rm9117

F

189.56

216.22

26.66

220.87

31.31

-

-

G2

(FTS)

300

 

Rm9118

F

190.53

197.13

6.6

199.87

9.34

-

-

0/3

0

Rm9119

F

187.80

191.75

3.95

198.35

10.55

-

-

Rm9120

F

189.20

198.65

9.45

207.10

17.9

-

-

G2

(STS)

300

 

Rm9121

F

181.96

203.94

21.98

207.53

25.57

-

-

0/3

0

Rm9122

F

176.30

198.66

22.36

202.16

25.86

-

-

Rm9123

F

186.62

188.08

1.46

191.57

4.95

-

-

F: Female        FTS: First Treatment Step            STS: Second Treatment Step             - : Nil         

 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the present study, The LD50 of the given test chemical is 2000 mg/kg. Thus, the test item is classified “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Globally Harmonized Classification system of Annex 2d of the Guideline, OECD 423 as there was two mortalities observed at 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity study was conducted to assess the toxicological profile of the test chemical in Wistar rats.

Undiluted test chemical was administered based on the density of the test item i.e., 1.01 g/cm3 at 27°C (as per TIDS) and the dose volume was 1.98 and 0.30 mL/kg to attain the doses of 2000 and 300 mg/kg body weight respectively.

The test item was administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 2000 mg/kg body weight. Clinical signs of Recumbency and ataxia were observed in two rats at 30 minutes to 4 hours, one rat died at 4 hours post dose and the other rat was found dead on day 2. The third rat was normal from day one till end of observation.

Hence as per Annex 2d, three female rats were tested at the next lower dose of 300 mg/kg body weight (G2-FTS). There were no clinical signs and there was no pre-terminal deaths observed. As per annex 2d of the guideline the treatment was continued with three additional rats at the same dose of 300 mg/kg bodyweight (0.30 mL/kg body weight) – G2-STS. There were no clinical signs and there was no pre-terminal deaths observed, as per the scheme – the Annex 2d of the guideline OECD 423, the dosing was stopped.

The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy.

Based on the results of the present study, The LD50 of the given test chemical is 2000 mg/kg. Thus, the test item is classified “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Globally Harmonized Classification system of Annex 2d of the Guideline, OECD 423 as there was two mortalities observed at 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
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:
study scientifically not necessary / other information available
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 study report.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The objective of this acute dermal toxicity study was to assess the toxicological profile of the test item on application as a single semi-occlusive dermal application to rats.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd., Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Females: 211.56 to 231.27 g
- Identification:By rat accession number. Identification of individual rats is by cage card and crystal violet colour body markings. The temporary body marking during acclimatization period was done with crystal violet. The rat accession numbers were allotted during the course of the study and was included in raw data and reported.
- Housing: Animals were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill. Additionally, polycarbonate rat huts were placed inside the cage as enrichment objects and were changed along with the cage once a week. Bedding: Steam sterilized corn cob was used and changed once a week along with the cage.
- Diet (e.g. ad libitum): Rat & Mice pellet feed, ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-DRF, eleven days for G2-DRF, thirteen days G3-DRF and fifteen days for G3-Main before treatment. Animals were observed once daily during acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24°C,
- Humidity (%): 66 to 68%,
- Air changes (per hr): air conditioned with adequate fresh air supply (12.4 to 13.0 air changes/hour).
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle

IN-LIFE DATES: From: 18 April 2018 To: 28 August 2018
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the hair on the dorsolateral thoracic surface of the skin was clipped (approximately 10 x 8 cm) with an electric clipper.
- % coverage: about 10% of body surface of the rat.
- Type of wrap if used: The applied area was covered with cotton gauze (size: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wound around the torso.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the applied area was washed with deionized water and wiped dry using clean towel.
- Time after start of exposure:24 hours
Duration of exposure:
24 hours
Doses:
Three treatment group
G1 – DRF - 200 mg/kg
G2 – DRF - 1000 mg/kg
G3 – DRF - 2000 mg/kg and G3-Main - 2000 mg/kg bw
No. of animals per sex per dose:
Three treatment group
G1 – DRF - 200 mg/kg - 1
G2 – DRF - 1000 mg/kg - 1
G3 – DRF - 2000 mg/kg - 1 and G3-Main - 2000 mg/kg bw - 2
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical examination and pre-terminal deaths - The animals were observed for clinical signs and pre-terminal deaths (mortality) once during first 30 minutes after application, and at hourly intervals for 6 hours after application on the day of treatment (day 1) and once daily during Days 2 to 15. In addition, treatment site at was observed 24, 48 and 72 hours after removal of test item using the Draize criteria (Refer Annexure 4 of this report). All rats were observed for changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

- Body weights - Individual body weights of animals were recorded on test days 1 (Pre-application), 8 (7 days post application), and 15 (14 days post application).

- Necropsy of survivors performed: yes, at the end of the observation period, all rats were euthanised and exsanguinated under isoflurane anesthesia and subjected to detailed necropsy by an experienced prosector and the findings were recorded. Microscopic examination was not carried out as no gross pathological changes were observed.
Statistics:
not specified
Preliminary study:
Dose range finding study - An initial starting dose of 200 mg/kg body weight was tested with 1 female rat (dose range finding study). As there was no mortality at this dose range finding study as per Annex 2 of the guideline the dose range finding study was continued with 1 female rat (dose range finding study) at the dose of 1000 mg/kg body weight. There was no mortality, hence the dose range finding study was continued with 1 female rat (dose range finding study) at the dose of 2000 mg/kg body weight, there was no mortality. The main study was conducted further with 2 female rats at the dose of 2000 mg//kg body weight to confirm the classification. There was no test item-related mortality. The subsequent dosing was done approximately 2, 4, 6 days after the previous dosing. The sequence was followed as per the details provided in the Annexure 3 of this report.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no pre-terminal deaths (mortality) observed during the study.
Clinical signs:
There were no clinical signs observed during the study.
Body weight:
All rats gained body weight throughout the observation period.
Gross pathology:
No abnormality was detected at necropsy.
Other findings:
not specified

TABLE 1.            Individual body weight, body weight changes and pre-terminal deaths

Group and

Dose

(mg/kg body weight)

Rat

No.

S

e

x

Body weight (g)

Pre-terminal deaths

Initial

(Day 1 - at treatment)

8th  

day

Weight change

(day 8 – Initial)

15th

day

Weight change

(day 15 – Initial)

G1 and

200

DRF

Rm9127

F

231.27

234.29

3.02

243.60

12.33

0

G2 and

1000

DRF

Rm9128

F

218.19

221.86

3.67

225.45

7.26

0

G3 and

2000

DRF

Rm9129

F

211.56

213.40

1.84

217.86

6.3

0

G3 and

2000

Main study

Rm9130

F

214.99

220.21

5.22

230.41

15.42

0

Rm9131

F

213.42

218.17

4.75

227.89

14.47

0

 DRF: Dose Range Finding   F: Female

 

 

   

Interpretation of results:
other: Not classified
Conclusions:
Based on the present study results, the acute dermal LD50 of the given test chemical is >2000 mg/kg body weight in female Wistar rats. The test item does not classified for acute dermal toxicity.
CLP classification "Not classified”.
Executive summary:

The acute dermal toxicity study was conducted as per OECD Guideline 402 (Acute Dermal Toxicity) tested in 5 females (3 females for dose range finding study followed by 2 females for main study) Wistar rats at the doses of 200, 1000 and 2000 mg/kg body weight.

Based on the individual body weight, the undiluted test item at the doses of 200 (0.20 mL/kg body weight), 1000 (0.99 mL/kg body weight) and 2000 (1.98 mL/kg body weight) - based on the density of the test item 1.01 g/cm3 (as per TIDS provided by the sponsor) was applied directly to the clipped skin of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wound around the torso. The test item contact period with the skin was for 24 hours. After the 24 hours contact period, the dressing was removed and the applied area was washed with deionized water and wiped dry using clean towels.

All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality. There was no skin reaction observed at test item applied area. Body weight was measured on days 1, 8 and 15 and all rats gained weight during experimental period. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy.

Based on the present study results, the acute dermal LD50 of the given test chemical is >2000 mg/kg body weight in female Wistar rats. The test item does not classified for acute dermal toxicity.

CLP classification "Not classified”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
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, 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 rats, mice and guinea pigs for test chemical. The studies are summarized as below –

 

The acute oral toxicity study was mentioned in study report and conducted to assess the toxicological profile of the test chemical in Wistar rats.

Undiluted test chemical was administered based on the density of the test item i.e., 1.01 g/cm3 at 27°C (as per TIDS) and the dose volume was 1.98 and 0.30 mL/kg to attain the doses of 2000 and 300 mg/kg body weight respectively.

The test item was administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 2000 mg/kg body weight. Clinical signs of Recumbency and ataxia were observed in two rats at 30 minutes to 4 hours, one rat died at 4 hours post dose and the other rat was found dead on day 2. The third rat was normal from day one till end of observation.

Hence as per Annex 2d, three female rats were tested at the next lower dose of 300 mg/kg body weight (G2-FTS). There were no clinical signs and there was no pre-terminal deaths observed. As per annex 2d of the guideline the treatment was continued with three additional rats at the same dose of 300 mg/kg bodyweight (0.30 mL/kg body weight) – G2-STS. There were no clinical signs and there was no pre-terminal deaths observed, as per the scheme – the Annex 2d of the guideline OECD 423, the dosing was stopped.

The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy.

Based on the results of the present study, The LD50 of the given test chemical is 2000 mg/kg. Thus, the test item is classified “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Globally Harmonized Classification system of Annex 2d of the Guideline, OECD 423 as there was two mortalities observed at 2000 mg/kg body weight.

 

The above study report is supported with another study mentioned in different publications, handbooks, authoritative databases and secondary database for the given test chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 1600 and 2000 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 2000 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 2000 mg/kg bw, with 95% confidence limits of 1700–2300 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

These studies are contradicted with the data available in publication and secondary report for the test chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 2.0-5.0 ml/kg bw. The given test chemical was dissolved in 20-45% Sunflower oil and administered via oral route. Animals were observed for mortality. 50% mortality was observed at 2675 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 2675 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

The above contradicted study data is supported with another study available in handbook, authoritative database and secondary report for the given test chemical and conducted on mice at the dose concentration of 2.0-5.0 ml/kg bw. The given test chemical was dissolved in 20-45% Sunflower oil and administered via oral route. Animals were observed for mortality. 50% mortality was observed at 2675 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 2675 mg/kg bw, when mice were treated with the given test chemical via oral route.

 

This study is further supported with the data available in handbook, authoritative database and secondary report for the given test chemical and conducted on guinea pigs at the dose concentration of 2.0-5.0 ml/kg bw (approximately equivalent to 2088-5020 mg/kg). The given test chemical was dissolved in 20-45% Sunflower oil and administered via oral route. Animals were observed for mortality. 50% mortality was observed at 2675 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 2675 mg/kg bw, when guinea pigs were treated with the given test chemical via oral route.

Thus, based on the above summarised studies on test chemical, it can be concluded that 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 in “Category 4” for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 0.024 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

 

Acute Dermal Toxicity:

In different studies, the given test chemical has 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 test chemical. The studies are summarized as below -

 

The acute dermal toxicity study was conducted as per OECD Guideline 402 (Acute Dermal Toxicity) tested in 5 females (3 females for dose range finding study followed by 2 females for main study) Wistar rats at the doses of 200, 1000 and 2000 mg/kg body weight.

Based on the individual body weight, the undiluted test item at the doses of 200 (0.20 mL/kg body weight), 1000 (0.99 mL/kg body weight) and 2000 (1.98 mL/kg body weight) - based on the density of the test item 1.01 g/cm3 (as per TIDS provided by the sponsor) was applied directly to the clipped skin of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wound around the torso. The test item contact period with the skin was for 24 hours. After the 24 hours contact period, the dressing was removed and the applied area was washed with deionized water and wiped dry using clean towels.

All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality. There was no skin reaction observed at test item applied area. Body weight was measured on days 1, 8 and 15 and all rats gained weight during experimental period. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy.

Based on the present study results, the acute dermal LD50 of the given test chemical is >2000 mg/kg body weight in female Wistar rats. The test item does not classify for acute dermal toxicity. CLP classification "Not classified”.

 

Another study mentioned in publications, authoritative databases and secondary report was carried out to determine the acute dermal toxicity dose by using the given test chemical in rabbits at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality and clinical signs. No mortality was observed at 5000 mg/kg bw in treated animals. The only clinical sign observed was anorexia. Hence, the LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

 

Thus, based on the above summarised studies for test chemical, it can be 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.

 

Justification for classification or non-classification

Based on the above studies for the test chemical, it can be concluded that LD50 value is between >300 - ≤ 2000 mg/kg bw, for acute oral toxicity and the LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this range and value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral toxicity and cannot be classified for acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.