α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats for the given test chemical. The studies concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified 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 2.01E-17 mm Hg. 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 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

The aim of this study was to assess the toxicity potential of the given test chemical after single oral administration in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation:8- 10 weeks at the time of dosing.
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight at study initiation:Minimum: 131 g Maximum: 160 g (Individual body weights were within ± 7% prior to treatment after overnight fasting)
- Fasting period:were fasted for 16 to 18 hours, prior to dosing .
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding:All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 25/2014.
- 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. Batch No 400004..
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period:Animal nos. 1-3 were acclimatized for 5 days and 4-6 for 11 days prior to administration of the test item..

ENVIRONMENTAL CONDITIONS
-Temperature: Minimum: 19.80°C Maximum: 23.20°C
-Relative humidity:Minimum: 48.70 % Maximum: 69.20 %
-Light-dark-rhythm:12:12
-Air Changes: More than 12 changes per hour

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage):10 ml

Doses:

G1 = 2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
AAt the end of 14 day observation period, all surviving rats were euthanised by overdose of CO2 for external and internal observations.
- Other examinations performed: Clinical Observation - After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the six animals were observed once a day during the 14 day observation period.
Mortality - All the animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight - All the rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.
Pathology - At the end of 14 day observation period, all surviving rats were euthanised by overdose of CO2 for external and internal observations

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed througout the experimentation period

Clinical signs:

other: At 2000 mg/kg, animal no. 1 and 4 were observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours and on day 1 post dosing while additionally, animal no. 1 was observed with mild lethargy on day 2 and animal no. 4 was observed with mild diarrhea at 1 and

Gross pathology:

No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice

Other findings:

not specified

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

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	G1/ 2000	135	160	177	18.52	31.11
2		146	180	199	23.29	36.30
3		137	143	172	4.38	25.55
4		147	166	182	12.93	23.81
5		160	190	206	18.75	28.75
6		131	161	183	22.90	39.69

Key:- = Not Applicable

 

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

Sex:Female

Group/ Dose (mg/kg)		Rats Body Weight (g)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ 2000	Mean	142.67	166.67	186.50	16.79	30.87
	SD	10.56	16.49	13.19	7.15	6.17
	n	6	6	6	6	6

Keys:SD = Standard Deviation, n = Number of Animals

Keys:- = Not applicable, 1 = Normal, 2 = Found dead, 4 = Abdominal breathing, 145 = Salivation,      155 = Sternal recumbency, 166 = Tremors, + = Mild, ++ = Moderate

Interpretation of results:

other: Not classified

Conclusions:

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibits acute oral toxicity in as per CLP criteria of classification

Executive summary:

Acute oral toxicity study was performed as per OECD No. 423 by using the given test chemical in Rats. Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all six animals was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, animal no. 1 and 4 were observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours and on day 1 post dosing while additionally, animal no. 1 was observed with mild lethargy on day 2 and animal no. 4 was observed with mild diarrhea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 2 was observed with normal clinical signs at 30 minutes, mild lethargy at 1, 2, 3 and 4 hours and mild diarrhoea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 3 was observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours, day 1, 2 and 3 and mild diarrhoea at 2 hours, followed by normal clinical signs till day 14. Animal no. 5 was observed with mild lethargy at 30 minutes, 1, 2, 3 and 4 hours and mild diarrhoea at 1, 2, 3 and 4 hours, followed by normal clinical signs till day 14. Animal no. 6 was observed normal clinical signs at 30 minutes, 1, 2, 3 and 4 hours and mild lethargy on day 1 and 2, followed by normal clinical signs till day 14.

No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifce.

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibits acute oral toxicity in as per CLP criteria of classification

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.

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

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 the given test chemical after single dose application by dermal route in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility.
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight (Prior to Treatment)::Male:Minimum: 242 g and Maximum: 262 g (Prior to Treatment)Female:Minimum: 221 g and Maximum: 249 g
- 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:Minimum: 19.80 °C Maximum: 23.20 °C
-Relative humidity:Minimum: 50.60% Maximum: 61.10%
-Light-dark-rhythm:12:12
-Air Changes:More than 12 changes per hour

Type of coverage:

occlusive

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 rat.
- Type of wrap if used:The test item was held in the contact with the skin with a 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

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

10 (Five per sex)

Control animals:

not specified

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.
-Mortality - Animals were observed twice daily for any mortality during the experimental period
- Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14..
other: -Pathology
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.

Statistics:

No statistical analysis was performed since the study was terminated with limit test.

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Non toxic to animals

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:

other: All animals were observed with normal clinical signs throughout the experimental period.

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Other findings:

not specified

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	262	260	289	-0.76	10.31
2		242	258	281	6.61	16.12
3		251	269	300	7.17	19.52
4		260	271	302	4.23	16.15
5		258	274	310	6.20	20.16
6	Female	228	231	240	1.32	5.26
7		221	219	225	-0.90	1.81
8		249	241	246	-3.21	-1.20
9		224	216	218	-3.57	-2.68
10		230	231	240	0.43	4.35

                                                                                                   

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
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

Keys: 1 = Normal

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:

Under the condition of the study, the acute dermal median lethal dose (LD50) of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.

Executive summary:

Acute dermal toxicity study was performed as per OECD No. 402 by using the given test chemical in Wistar Rats. 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 by single dermal application and observed for 14 days after treatment. On test day 0, anamount oftestitem 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.

All the animals were observed with normal clinical signs throughout the experimental period. No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.

In males, mean body weight was observed with increase on day 7 and 14, as compared to day 0. In females, mean body weight was observed with decrease on day 7 and increase 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.

Under the condition of the study, the acute dermal median lethal dose (LD50) of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals. 

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 for the given test chemical. The studies are summarized as below –

 

The reported study was mentioned in study report and conducted to assess the toxicological profile of the test chemical as per OECD No. 423 in Rats. Six female Wistar rats were selected for acute oral toxicity study.

The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all six animals was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, animal no. 1 and 4 were observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours and on day 1 post dosing while additionally, animal no. 1 was observed with mild lethargy on day 2 and animal no. 4 was observed with mild diarrhoea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 2 was observed with normal clinical signs at 30 minutes, mild lethargy at 1, 2, 3 and 4 hours and mild diarrhoea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 3 was observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours, day 1, 2 and 3 and mild diarrhoea at 2 hours, followed by normal clinical signs till day 14. Animal no. 5 was observed with mild lethargy at 30 minutes, 1, 2, 3 and 4 hours and mild diarrhoea at 1, 2, 3 and 4 hours, followed by normal clinical signs till day 14. Animal no. 6 was observed normal clinical signs at 30 minutes, 1, 2, 3 and 4 hours and mild lethargy on day 1 and 2, followed by normal clinical signs till day 14.

No external and internal gross pathological examination was seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice.

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibits acute oral toxicity in as per CLP criteria of classification

 

The above study report is supported with the data available in another study report and the study was conducted by using the given test chemical with the compliance of OECD Guideline-423 for testing of chemicals. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test compound and vehicle control group each having three animals.

The study was conducted stepwise as follow: Starting dose 2000 mg/kg body weight: Step-I - The test compound was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10 ml/kg) to three female rats. However; vehicle control group treated with the distilled water at the dose level of 10 ml/kg b.wt.  The treated animals were closely observed for clinical signs of intoxication during first four hours of test compound administration. Thereafter, all the animals were observed periodically at one hour interval for 24 hrs and once daily for a period of 14 days.  The necropsy was performed on all animals at the termination of the study.

All the Wistar albino rats which were treated with the test compound observed normal without any mortality and clinical signs of toxicity. Furthermore, No clinical signs and mortality were observed in vehicle control group. The necropsy finding did not reveal any gross pathological changes. Furthermore, no gross pathological change was observed in vehicle control group.

In Step -II: After 72 hrs, the result of step-I was confirmed by administration of same dose level (2000 mg/kg. b.wt) of test compound in additional three animals of same sex (OECD-423 guidelines). The test compound administered at the dose level of 2000 mg/kg b.wt did not produce any mortality and clinical sign of intoxication throughout the observation period of 14 days in treated Wistar albino rats. The test compound did not elicit any gross pathological changes in animals sacrificed at the end of experimentation. Based on the results obtained from present investigation, it can be concluded that the test compound is non- toxic to Wistar albino rats at the dose level of 2000 mg/kg b.wt.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified 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 2.01E-17 mm Hg. 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 for test chemical. The studies are summarized as below -

 

The reported study was mentioned in study report and was performed to determine acute dermal toxicity dose as per OECD No. 402 by using the given test chemical in Wistar Rats. 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 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 porous gauze dressing was put on to the intact skin of clipped area.

All the animals were observed with normal clinical signs throughout the experimental period. No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.

In males, mean body weight was observed with increase on day 7 and 14, as compared to day 0. In females, mean body weight was observed with decrease on day 7 and increase 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.

Under the condition of the study, the acute dermal median lethal dose (LD50) of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals. 

 

Another study mentioned in study report was carried out to determine the acute dermal toxicity dose by using the given test chemical according to OECD guideline 402 for testing of chemicals on Wistar albino rats.

The summary of the study was as follows- LIMIT TEST (2000 mg/kg b.wt): Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound was applied dermally at the dose level of 2000 mg/kg b.wt to each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals at the termination of the study.

The test compound applied at the dose level of 2000 mg/kg b.wt in Wistar albino rats did not show any mortality as well as clinical signs of toxicity throughout the observation period of 14 days. The necropsy was conducted on all the animals at the end of observation period did not show any gross pathological changes.  

CONFIRMATORY TEST: After 72 hrs, confirmatory test was conducted in same species of animals to confirm result obtained from the limit test (OECD-402 guidelines for testing of chemicals). Ten healthy Wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test drug was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals at termination of the study.

No mortality was recorded after administration of test compound at the dose level of 2000 mg/kg b.wt. The test compound did not elicit any clinical signs of toxicity during the entire observation period. No skin reaction was observed after 24th hrs. of patch removal. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase in weight.

Based on the results obtained from present investigation, it can be concluded that the acute dermal LD50 was considered to be >2000 mg/kg b.wt. when Wistar albino rats was treated with the given test compound applied by dermal route.

 

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 >2000 mg/kg bw, for acute oral toxicity and acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral and acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.