Registration Dossier

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 >5000 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 dose (LC50) was considered based on different studies conducted on rats and mice for the test chemical. The studies concluded that the LC50 value is >5 mg/L (>5000 mg/m3), for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

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 studies concluded that the 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.

Reference

Endpoint:: acute toxicity: oral
Type of information:: experimental study
Adequacy of study:: key study
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: data from handbook or collection of data
Justification for type of information:: Data from authoritative database
Qualifier:: equivalent or similar to guideline
Guideline:: other: As mentioned below
Principles of method if other than guideline:: Acute oral toxicity study of test chemical was performed in rats
GLP compliance:: not specified
Test type:: other: not specified
Limit test:: yes
Species:: rat
Strain:: not specified
Sex:: male/female
Details on test animals or test system and environmental conditions:: No data available
Route of administration:: oral: unspecified
Vehicle:: unchanged (no vehicle)
Details on oral exposure:: No data available
Doses:: As mentioned in table below
No. of animals per sex per dose:: Total :10
male:5
female:5
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: No data available
- Other examinations performed: clinical signs and postmortem examination
Were performed
Statistics:: No data available
Preliminary study:: No data available
Sex:: male/female
Dose descriptor:: LD50
Effect level:: > 5 000 mg/kg bw
Based on:: test mat.
Remarks on result:: other: No mortality was observed
Mortality:: No mortality was observed
Clinical signs:: other: No data available
Gross pathology:: No data available
Other findings:: Acute oral studies indicate that LD50 values of test chemical in the rat are proportional to their free test substance content.
Interpretation of results:: other: Not classified
Conclusions:: The LD50 value was considered to be >5000 mg/kg,when male and female rats were treated with test chemical orally.
Executive summary:: Acute oral toxicity test was carried out for different grades of test chemical. Groups of five male and five female rats were given single oral doses of the test materials. The animals were observed at frequent intervals for the first day and then at least daily over a 14-day observation period. All the animals dying during this period and the surviving animals, which were killed on day 14, were subjected to a post mortem examination to note any microscopic abnormalities.Administration of different grades of test chemical in male and female rat resulted in no or minimum, sign of toxicity at doses up to 5000 mg/kg. Hence,The LD50 value was considered to be >5000 mg/kg,when male and female rats were treated with test chemical orally.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Reference

Endpoint:

acute toxicity: inhalation

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 of various test substances

Justification for type of information:

Data for the test chemical is summarized based on the various chemicals

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 2 acute inhalation toxicity studies as - WoE-2 and WoE-3
Acute Inhalation 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:

other: 1. mouse 2. rat

Strain:

other: 1. not specified 2. not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

1. not specified
2. not specified

Route of administration:

other: 1. inhalation: vapour 2. inhalation

Type of inhalation exposure:

other: 1. not specified 2. not specified

Vehicle:

other: 1. not specified 2. not specified

Remark on MMAD/GSD:

1. not specified
2. not specified

Details on inhalation exposure:

1. not specified
2. not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

2 h

Remarks on duration:

not specified

Concentrations:

1. Range between 2,000 and 17,000 mg/m³
2. 5 mg/l in air (5000 mg/m3)

No. of animals per sex per dose:

1. not specified
2. not specified

Control animals:

not specified

Details on study design:

1. - Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for mortality and clinical signs.
2. not specified

Statistics:

1. not specified
2. not specified

Preliminary study:

1. not specified
2. not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

7 570 mg/m³ air

Based on:

test mat.

Exp. duration:

2 h

Remarks on result:

other: 50% mortality was observed

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

1. 50% mortality was observed
2. No mortality was observed at dose 5 mg/l in air in treated rats

Clinical signs:

other: 1. Initially all animals exhibited slight inflammations of the eyes and the respiratory tract as well as agitation, followed by a loss of activity. After exposures to values up to 4,000 mg/m³ these symptoms were reversible after the termination of the exp

Body weight:

1. not specified
2. not specified

Gross pathology:

1. The dissection revealed injuries in several organs (vascularisation, bleeding, dystrophic changes).
2. not specified

Other findings:

1. not specified
2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation the test chemical cannot be classified for acute inhalation toxicity, as the LC50 value is >5 mg/L (>5000 mg/m3).

Executive summary:

In different studies, the given test chemical has been investigated for acute inhalation 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 acute inhalation toxicity study was conducted by using test chemical in mice at the concentration range between 2,000 and 17,000 mg/m³. Animals were observed for mortality and clinical signs. Necropsy was performed. 50% mortality was observed in treated mice at 7570 mg/m³ when exposed for 2 hours. Initially all animals exhibited slight inflammations of the eyes and the respiratory tract as well as agitation, followed by a loss of activity. After exposures to values up to 4,000 mg/m³ these symptoms were reversible after the termination of the exposure. Higher concentrations caused further CNS and neuromuscular symptoms (weak reflexes, unsteady gait, respiratory disorders, and tonic-clonic spasms). The dissection revealed injuries in several organs (vascularisation, bleeding, dystrophic changes). Therefore, LC50 was considered to be 7570 mg/m³, when mice were exposed to test chemical via inhalation by vapour for 2 hour exposure.

The above study is supported with another study conducted on rats for the test chemical. The acute inhalation toxicity study was conducted by using test chemical in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with test chemical by inhalation route.

Thus, based on the above summarised studies on test chemical, it can be concluded that LC50 value is >5 mg/L (>5000 mg/m3). Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

7 570 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from authoritative database

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study of test chemical was performed in rats

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

24hr

Doses:

As mentioned in table below

No. of animals per sex per dose:

Total :10
male:5
female:5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: No data available
- Other examinations performed: clinical signs, body weight, histopathology were observed

other: To prevent the animals from gaining access to the sites of application (and hence
Probably ingesting the test material) acetate collars were placed around each rat's neck for a further 24 hours.

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was not observed at given dose

Mortality:

Mortality observed only for test chemical In IHS (7. 5%).
At 2000 mg/kg- 3/10
At 2500 mg/kg - 9/10
At 3000 mg/kg - 9/10
At 4000 mg/kg - 10/10

Clinical signs:

other: As mentioned in table below

Gross pathology:

No data available

Other findings:

No data available

SR.NO	Resin type	Clinical signs
1	Unground Phenol Formaldehyde resol	Slight sedation and ruffled fur. Mild redness swelling on test site.
2	Resorcinol Phenol Formaldehyde Novolak In IHS (7. 5%)	Sedation and ruffled fur. mild redness swelling on test site
3	Phenol Formaldehyde Resol In Ethanol (43%)	Nothing abnormal detected
4	Phenol Formaldehyde Resol In IHS (19. 7%)	Slight sedation and ruffled fur. and curved posture
5	Phenol Formaldehyde liquid Resol	Sedation and ruffled fur. mild redness swelling on test site
6	Phenol Formaldehyde liquid Resol	Nothing abnormal detected. Skin stained at test site
7	Water Dilutable Phenol Formaldehyde Liquid Resol	Nothing abnormal detected. Well depend redness on test site on female animals for 24 hrs following patches removal.

Interpretation of results:

other: Not classified

Conclusions:

The LD50 value was considered to be >2000mg/kg bw, when rats were treated with test chemical by dermal application

Executive summary:

Acute dermal toxicity test was carried out for different grades of test chemical. Groups of five male and five female rats were exposed to single doses of selected resin applied to the skin under occlusion for 24 hours.A similar group, exposed to the patches alone, served as controls.The animals were observed for 14 days following exposure for signs of toxicity.No fatalities occurred, except at the higher treatment levels with test chemical in ethanol containing 23% free phenol, during the observation period although evidence of irritancy was noted with certain grades. Bodyweight gain was essentially similar in treated and control animals and no significant macroscopic changes were seen in the organs at autopsy.Dermal LD values for all the grades examined under the conditions of exposure, considered to exceed 2000 mg/kg. Hence, The LD50 value was considered to be >2000mg/kg bw, when rats were treated with test chemical by dermal application.

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 authoritative database.

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 –

Acute oral toxicity test was carried out for different grades of test chemical. Groups of five male and five female rats were given single oral doses of the test materials. The animals were observed at frequent intervals for the first day and then at least daily over a 14-day observation period. All the animals dying during this period and the surviving animals, which were killed on day 14, were subjected to a post mortem examination to note any microscopic abnormalities. Administration of different grades of test chemical in male and female rat resulted in no or minimum, sign of toxicity at doses up to 5000 mg/kg. Hence, the LD50 value was considered to be >5000 mg/kg, when male and female rats were treated with test chemical orally.

The above study is supported with another study for the test chemical. The acute oral toxicity test was conducted on rat to evaluate the lethal dose of test chemical. The Sprague dawley rats were dosed orally with dose concentration of 2510, 3160, 3980 and 5010 mg/kg to 20 male and female rats for 14 days. Body weight, mortality, clinical signs and gross pathology changes were observed. Mortality was observed on day 1. Weight loss in survivors, increasing weakness, salivation, ocular discharge, dyspnes, collapse and death occurred in the animals during study period. In gross pathology, Hemorrhagic lungs, liver discoloration, and acute gastrointestinal inflammation observed.50% mortality was observed at dose 2900 mg/kg. Hence, based on mortality, LD50 value was considered to be 2900 mg/kg bw, when rats were treated with test chemical orally.

These studies are supported with the study mentioned in database for the test chemical. The acute oral toxicity study was performed by using test chemical in male albino rats at the dose concentrations of 2150, 3160, 4640, 6810 and 10000 mg/kg bw. The given test chemical was dissolved as 0.5% solution of methylcellulose and administered via oral gavage route. The animals were observed for mortality and clinical signs for 7 days. Necropsy of survivors performed. Thompson moving average method was used to calculate LD50 value.

Death was preceded by coma. Animals at all dosage levels appeared depressed and exhibited lachrymation; ataxia; sprawling of the hind limbs; prone positions; depressed or absent placement, pain, and righting reflexes; tachycardia; and rapid and labored respiration. In addition, salivation was observed among the animals at the four higher dosage levels. The surviving animals appeared slightly depressed and exhibited slight lacrimation 24 hours following oral administration. At 48 hours, and daily thereafter, the surviving animas appeared normal. Gross pathology revealed the following observation, hemorrhagic lungs, irritation of the gastrointestinal tract and peritoneous, and congested kidneys and adrenals. Under the condiction of this, the lethal concentration (LD50) value for acute oral toxicity test was considered to be 3830 mg/kg bw (95% CI: 2930-5000 mg/kg bw), when male albino rats were treated with test chemical orally via gavage.

All the above studies are further supported with the study mentioned in database for the test chemical. The acute oral toxicity study of test chemical was conducted on mouse at the dose concentration of 9000 mg/kg bw. The test chemical was administered via oral route. All animals were maintained under close observation for recording toxic signs and time of death. Mortality was observed at a dose of 9000 mg/kg bw. Therefore, LD50 value was considered to be 9000 mg/kg bw, when mouse were treated with test chemical via oral route.

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:

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 mice for test chemical. The studies are summarized as below -

The acute inhalation toxicity study was conducted by using test chemical in mice at the concentration range between 2,000 and 17,000 mg/m³. Animals were observed for mortality and clinical signs. Necropsy was performed. 50% mortality was observed in treated mice at 7570 mg/m³ when exposed for 2 hours. Initially all animals exhibited slight inflammations of the eyes and the respiratory tract as well as agitation, followed by a loss of activity. After exposures to values up to 4,000 mg/m³ these symptoms were reversible after the termination of the exposure. Higher concentrations caused further CNS and neuromuscular symptoms (weak reflexes, unsteady gait, respiratory disorders, and tonic-clonic spasms). The dissection revealed injuries in several organs (vascularisation, bleeding, dystrophic changes). Therefore, LC50 was considered to be 7570 mg/m³, when mice were exposed to test chemical via inhalation by vapour for 2 hour exposure.

The above study is supported with another study conducted on rats for the test chemical. The acute inhalation toxicity study was conducted by using test chemical in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with test chemical by inhalation route.

Thus, based on the above summarised studies on test chemical, it can be concluded that LC50 value is >5 mg/L (>5000 mg/m3). Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

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 –

Acute dermal toxicity test was carried out for different grades of test chemical. Groups of five male and five female rats were exposed to single doses of selected resin applied to the skin under occlusion for 24 hours. A similar group, exposed to the patches alone, served as controls. The animals were observed for 14 days following exposure for signs of toxicity. No fatalities occurred, except at the higher treatment levels with test chemical in ethanol containing 23% free phenol, during the observation period although evidence of irritancy was noted with certain grades. Body weight gain was essentially similar in treated and control animals and no significant macroscopic changes were seen in the organs at autopsy. Dermal LD50 values for all the grades examined under the conditions of exposure, considered to exceed 2000 mg/kg. Hence, The LD50 value was considered to be >2000mg/kg bw, when rats were treated with test chemical by dermal application.

The above study is supported with another study conducted on rabbits for the test chemical. The acute dermal toxicity test was conducted on rabbit to evaluate the lethal dose of test chemical .The New Zealand albino rabbits were dosed dermally with dose concentration of 3160, 5010 and 7940 mg/kg to 4 male and female rats for 14 days. Body weight, mortality, clinical signs and gross pathology changes were observed. Mortality was seen in two days. Weight loss in survivors, increasing, collapse and death occurred in the animals during study period. In gross pathology, Hemorrhagic areas of the lungs, discoloration of liver, kidneys and spleen, enlarged gall bladder, and gastrointestinal inflammation observed. No mortality was observed at dose 5010 mg/kg. Hence, Based on mortality, LD50 value was considered to be >5010 mg/kg. When rabbits were treated with test chemical by dermal application.

These studies are supported with the study mentioned in database for the test chemical.In acute dermal toxicity study, male and female new Zealand white rabbits were treated with test chemical in the concentration of 3160, 5010 and 7940 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 3160 and 5010 mg/kg bw. Clinical signs like gastrointestinal peritonitis; behavioural food intake and somnolence (general depressed activity)(2 -3 days in survivors);increasing weakness, collapse and death were observed. Lungs and liver hypermia, kidney discoloration and gastrointestinal inflammation were observed in gross pathological observations. Therefore, LD50 value was considered to be >5010 mg/kg bw, when rabbits were treated with test chemical by dermal application.

All the above studies are further supported with the study mentioned in database for the test chemical. The acute dermal toxicity study of test chemical was conducted on rabbits at the dose concentration of 5010 mg/kg bw and 7940 mg/kg bw. The test chemical was administered dermally as a 40% suspension in corn oil. All animals were maintained under close observation for recording toxic signs and time of death .Clinical signs like reduced appetite was observed. No mortality was observed at a dose of 5010 and 7940 mg/kg bw. Therefore, LD50 value was considered to be >7940 mg/kg bw, when rabbits were treated with test chemical via dermal application.

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 dermal toxicity.

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; and LC50 value is >5 mg/L (>5000 mg/m3), for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral, acute inhalation and acute dermal toxicity.

SR.NO	Resin type	Clinical signs
1	Phenol Formaldehyde Novolak Ground With Hexamine (6%)	Tremors and convulsion in animal subsequent prostration with twitching and staining around the mouth & chin.
2	Phenol Formaldehyde Novolak Ground With Hexamine (9.1%)	Nothing abnormal detected.
3	Ground Phenol Formaldehyde Novolak Without Hexamine	Nothing abnormal detected.
4	Cashew Modified Phenol Formaldehyde Novolak Ground With Hexamine (7. 9%)	Slight Tremors in 4 animals. Salivation and resultant fur staining with evidence of gastro-intestinal disturbance.
5	Spray Dried Phenol Formaldehyde Resol	Seadation, Ruffled fur and arched posture.
6	Resorcinol Phenol Formaldehyde Novolak In Ethanol (7. 5%)	Seadation and convulsion with Ruffled fur and arched posture.
7	Phenol Formaldehyde Resol In Ethanol (43%)	Nothing abnormal detected.
8	Phenol Formaldehyde Resol In Ethanol (19. 7%)	Seadation and convulsion with Ruffled fur and arched posture.
9	Phenol Formaldehyde Resol In Ethanol (30%)	Transient salivation and transient staining.
10	Water Dilutable Phenol Formaldehyde Liquid Resol	Transient salivation (with associated staining) and body Tremors at all dose level. Some staining in urogenital region.
11	Phenol Formaldehyde Liquid Resol	Seadation, Ruffled fur, arched posture. Some convulsion at highest dose level
12	Phenol Formaldehyde Liquid Resol	Transient salivation and associated staining slight body tumor in one animal.
13	Phenol Formaldehyde Liquid Resol	Tumors and convulsion with prostration and twitching at both dose level. Salivation was seen in almost all animals. No treatment related microscopic change at autopsy in all surviving animals