Trisodium 8-hydroxypyrene-1,3,6-trisulphonate

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats and mice for the test chemical. The LD50 value is >15000 mg/kg bw. The study concluded that LD50 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 2.48E-023 Pa at 25°C. 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 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

Study period:

14.08.1972 to 31.08.1972

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Data is from study report.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute toxicology study was conducted by using the given test chemical in male Wistar rats.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

TNO/W.70, SPF

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: Adult, about 7 to 40 weeks old
- Weight at study initiation: average initial weight of 181 g (5000 mg/kg) or 134 g (15000 mg/kg).
- Housing: caged in groups of 5 males
- Diet (e.g. ad libitum): "Altromin 1324 - Housing Diet of Rats and Mouse "in pellet form
- Water (e.g. ad libitum): tap water ad libitum (drink bottles).
- Acclimation period: several days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%):50 ± 10%
- Air changes (per hr): about 10-fold air changes per hour
- Photoperiod (hrs dark / hrs light): twelve-fold He11 / Dunke1 rhythm (artificial lighting).

IN-LIFE DATES: From: 14.08. 1972 To: 31.08.1972

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

0.5% aqueous solution of methylcelulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5000 mg/kg and 15000 mg/kg
- Amount of vehicle (if gavage): 20 and 30 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 15000 mg/kg bw

Doses:

5000 and 15000 mg/kg bw

No. of animals per sex per dose:

10 male rats per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (14- (5000 mg / kg) or 7- (15000 mg / kg) -day)
- Frequency of observations and weighing: On the day of the application, twice a day (once on weekends during non-public holidays).
Body weight – Animals were weighed, before the application, after one week and at the end of the observation period in groups.
- Necropsy of survivors performed: yes, all died during the trial and all at the end of the trial, sacrificed in deep diethyl ether narcosis were pathologically anatomically assessed.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal of dose group 5000 mg/kg bw died within the first 24 hours after application. Due to of the lack of mortality in the high dose of 15000 mg/kg bw, a connection between the death of this animal and the administration of the test substance appears unlikely.

Clinical signs:

other: No symptoms were observed after single doses of 5000 and 15000 mg/kg.

Gross pathology:

Indications of fatty liver was observed in 5000 and 15000 mg/kg bw.

Other findings:

In the high dose group organs and muscles were colored by the substance.

Interpretation of results:

other: Not classified

Conclusions:

The acute oral toxicity dose (LD50) was considered to be >15000 mg/kg bw, when 10 per dose male Wistar TNO/W.70, SPF rats were treated with the given test chemical via oral gavage route.

Executive summary:

The acute oral toxicity study was conducted by using the given test chemical in 10 per dose male Wistar TNO/W.70, SPF rats at the dose concentrations of 5000 and 15000 mg/kg bw.

The given test chemical was dissolved in 0.5% aqueous solution of methylcellulose and administered as 20 and 30 ml/kg bw via oral gavage route.

Animals were observed for mortality, on the day of the application, twice a day (once on weekends during non-public holidays). Animals were weighed, before the application, after one week and at the end of the observation period in groups. Necropsy of survivors performed. All animals that died during the trial and all at the end of the trial, sacrificed in deep diethyl ether narcosis were pathologically anatomically assessed.

One animal of dose group 5000 mg/kg bw died within the first 24 hours after application. Due to of the lack of mortality in the high dose of 15000 mg/kg bw, a connection between the death of this animal and the administration of the test substance appears unlikely. No symptoms were observed after single doses of 5000 and 15000 mg/kg. Growth was not delayed in either treatment group. Indications of fatty liver was observed in 5000 and 15000 mg/kg bw. In the high dose group organs and muscles were colored by the substance.

Under the condition of the study, the LD50 value was considered to be >15000 mg/kg bw, when 10 per dose male Wistar TNO/W.70, SPF rats were treated with the given test chemical via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

15 000 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data from various test chemicals

Justification for type of information:

Data is summarized based on the available information from various test chemicals.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on 3 acute dermal toxicity studies as- WoE 2, WoE 3 and WoE 4.
Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

2. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight ranges of approximately 239.1 to 272.5 grams at initiation of dosing were used.
Body weights at the start : Maln Mean: 269.94 g (= 100 %); Minimum : 266.4 g (- 1.31 %); Maximum : 272.5 g (+ 0.95 %)
Female Mean: 244.56 g (= 100 %); Minimum : 239.1 g (- 2.23 %); Maximum : 250.4 g (+ 2.39 %)
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.3 degree centigrade.
- Humidity (%): 55.7% to 59.6%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 30-09-2016 to 15-10-2016
3. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight ranges of approximately 210.2 to 245.4 grams at initiation of dosing were used.
Body weights at the start : Male Mean: 240.40 g (= 100 %); Minimum : 234.6 g (- 2.41 %); Maximum : 245.4 g (+ 2.08 %)
Female Mean: 215.98 g (= 100 %); Minimum : 210.2 g (- 2.68 %); Maximum : 220.6 g (+ 2.14 %)
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at 20.1 to 21.9 degree centigrade.
- Humidity (%): Room humidity was maintained at 55.5% to 59.2%.
- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
4. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: [no]
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight ranges of approximately 201.4 to 232.7 grams at initiation of dosing were used.
Body weights at the start : Male Mean: 222.62 g (= 100 %); Minimum : 216.7 g (- 2.66 %); Maximum : 232.7 g (+ 4.53 %)
Female Mean: 207.88 g (= 100 %); Minimum : 201.4 g (- 3.12 %); Maximum : 218.1 g (+ 4.92 %)
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at 20.1 to 21.9 degree centigrade.
- Humidity (%): Room humidity was maintained at 55.5% to 59.2%.
- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

Type of coverage:

occlusive

Vehicle:

other: 2. water 3. water 4. unchanged (no vehicle)

Details on dermal exposure:

2. TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes
3. TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw.
4. TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

2. 24 hours
3. 24 hours
4. 24 hours

Doses:

2. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
3. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
4. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).

No. of animals per sex per dose:

2. 10 (5/sex).
3. 10 (5/sex).
4. 10 (5/sex).

Control animals:

not specified

Details on study design:

2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.
Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.
Gross Pathology: Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
3. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.
Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.
Gross Pathology: Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
4. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.

The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

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

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

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

Statistics:

2. not specified
3. not specified
4. not specified

Preliminary study:

2. not specified
3. not specified
4. not specified

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
Sex : Female Group I – Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
3. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
Sex : Female Group I – Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
4. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
Sex : Female Group I – Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.

Clinical signs:

other: 2. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not resul

Gross pathology:

2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
3. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
4. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.

Other findings:

2. - Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
3. - Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
4. - Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.

Executive summary:

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 designed and conducted to determine the acute dermal toxicity profile of the given test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

The above study is supported with another study mentioned in report and performed as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats 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 toxicity by the dermal route.

Both the above studies are further supported with the study mentioned in study report for the test chemical. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats 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 test chemical does not exhibits acute toxicity by the dermal route.

 

Thus, based on the above summarised studies on 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from 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 and mice for test chemical. The studies are summarized as below -

 

The reported acute oral toxicity study was mentioned in study report and conducted by using the given test chemical in 10 per dose male Wistar TNO/W.70, SPF rats at the dose concentrations of 5000 and 15000 mg/kg bw.

The given test chemical was dissolved in 0.5% aqueous solution of methylcellulose and administered as 20 and 30 ml/kg bw via oral gavage route.

Animals were observed for mortality, on the day of the application, twice a day (once on weekends during non-public holidays). Animals were weighed, before the application, after one week and at the end of the observation period in groups. Necropsy of survivors performed. All animals that died during the trial and all at the end of the trial, sacrificed in deep diethyl ether narcosis were pathologically anatomically assessed.

One animal of dose group 5000 mg/kg bw died within the first 24 hours after application. Due to of the lack of mortality in the high dose of 15000 mg/kg bw, a connection between the death of this animal and the administration of the test substance appears unlikely. No symptoms were observed after single doses of 5000 and 15000 mg/kg. Growth was not delayed in either treatment group. Indications of fatty liver was observed in 5000 and 15000 mg/kg bw. In the high dose group organs and muscles were colored by the substance.

Under the condition of the study, the LD50 value was considered to be >15000 mg/kg bw, when 10 per dose male Wistar TNO/W.70, SPF rats were treated with the given test chemical via oral gavage route.

The above study report is supported with another study mentioned in publication for the given test chemical. In acute oral toxicity study, rats were treated with the given test chemical at the dose concentration of 15000 mg/kg bw orally. Animals were observed for mortality. No mortality was observed in treated rats at 15000 mg/kg bw. Therefore, the LD50 value was considered to be >15000 mg/kg bw, when rats were treated with the given test chemical orally.

 

These studies are supported with the data available in secondary report for the test chemical. In an acute oral toxicity study, rats were treated with the given test chemical at the dose concentration of 16000 mg/kg bw orally. Animals were observed for mortality. 50% mortality was observed in treated rats at 16000 mg/kg bw. Therefore, the LD50 value was considered to be 16000 mg/kg bw, when rats were treated with the given test chemical orally.

 

All the above studies are further supported with the study mentioned in report for the given test chemical. In an acute oral toxicity study, mice were treated with the given test chemical at the dose concentration of 10500 mg/kg bw orally. Animals were observed for mortality. 50% mortality was observed in treated mice at 10500 mg/kg bw. Therefore, the LD50 value was considered to be 10500 mg/kg bw, when mice were treated with the given test chemical orally.

 

Thus, based on the above summarised studies 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 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 2.48E-023 Pa at 25°C. 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 designed and conducted to determine the acute dermal toxicity profile of the given test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

The above study is supported with another study mentioned in report and performed as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats 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 toxicity by the dermal route.

Both the above studies are further supported with the study mentioned in study report for the test chemical. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats 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 test chemical does not exhibits acute toxicity by the dermal route.

 

Thus, based on the above summarised studies on 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 on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral 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.