Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) for Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is >2000 mg/kg bw.Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride cannot be classified for acute oral toxicity. 

Acute Inhalation toxicity: 

Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride has very low vapour pressure (1.23E-19 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) for Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is >2000 mg/kg bw.Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride 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:

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 read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally and functionally similar read across 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 oral toxicity studies as - WoE-2 and WoE-3. Acute Oral 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

Specific details on test material used for the study:

- Name of test material : Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride- Molecular formula : C35H46ClN5O4- Molecular weight : 636.232 g/mol- Smiles notation : C(CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O)[N+](C)(C)CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O.[ClH-]- InChl : 1S/C35H46N5O4.ClH/c1-7-38(8-2)32-16-12-28(13-17-32)24-30(26-36)34(41)43-22-11-20-40(5,6)21-23-44-35(42)31(27-37)25-29-14-18-33(19-15-29)39(9-3)10-4;/h12-19,24-25H,7-11,20-23H2,1-6H3;1H/q+1;/p-1/b30-24+,31-25+;- Substance type: Organic- Physical state: Liquid

Species:

rat

Strain:

other: 1. Wistar 2. not specified

Sex:

female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS- Source: In-house animals, bred at Animal House, sa-FORD.- Age at study initiation:10-11 weeks at the time of dosing.- Weight at study initiation: Minimum: 142 g Maximum: 180 g (Individual body weights were within ± 20 % prior to treatment after overnight fasting)- Fasting period before study: overnight fasting- Housing: The animals were housed individually in polycarbonate cages (size 37 [cm] x 21 [cm], height 20 [cm]). Bedded with corn cobs (Sparconn Life Sciences Bangalore) SPAR – 32 /2016 and marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number, experimental start, dosing date and completion date.experimental room floor and work tops were swept and mopped with disinfectant solution every day. 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 Nos.: 040316 and 040416.- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles- Acclimation period: Animal nos. 01-03 were acclimatized for 6 days, 04-06 for 12 days, 07-09 for 17 days and 10-12 for 6 days prior to administration of the test item. ENVIRONMENTAL CONDITIONS- Temperature (°C): Minimum: 19.30 °C, Maximum: 23.10 °C- Humidity (%):Minimum, 43.30% Maximum: 67.00%- Air changes (per hr): More than 12 changes per hour- Photoperiod (hrs dark / hrs light):12 hour light and 12 hour dark2. not specified

Route of administration:

other: 1. oral: gavage 2. oral: unspecified

Vehicle:

other: 1. corn oil 2. not specified

Details on oral exposure:

1. Details on exposureVEHICLE- Concentration in vehicle: 300 and 2000 mg/kg body weight- Amount of vehicle (if gavage): 10 ml/kg body weight- Justification for choice of vehicle: Corn oil (Batch No- MR020116-MP Biomedicals) was selected as a vehicle based on solubility testing.- Lot/batch no. (if required):MR020116-MP MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight DOSAGE PREPARATION (if unusual): The test item formed a homogenous suspension in corn oil and hence, it was selected as a vehicle. The desired quantity of the test item (300 mg and 2000 mg) was added to the mortar and triturated using pestle. The vehicle (corn oil) was added to the mortar slowly and mixed well. The formulation was then transferred to a calibrated measuring cylinder. The stock concentration of 200 mg/ml and 30 mg/ml was achieved by making up the volume to 10 ml in the measuring cylinder. CLASS METHOD (if applicable)- Rationale for the selection of the starting dose:The starting dose level was that, which most likely to produce mortality in some of the dosed animals. The starting dose level was selected as 300 mg/kg body weight as no information available in the pesticide manual. The time interval between treatment groups was determined by the onset, duration, and severity of toxic signs. Treatment of animals at the next dose was delayed until confidence of survival of the previously dosed animals is attained.2. not specified

Doses:

1. 300 and 2000 mg/kg body weight2. 10000 mg/kg

No. of animals per sex per dose:

1. Total: 12; 300 mg/kg bw (Step -I): 4; 300 mg/kg bw (Step -II): 4; 2000 mg/kg bw (Step -III): 4; 2000 mg/kg bw (Step -IV): 42. not specified

Control animals:

not specified

Details on study design:

1. Details on study design- Duration of observation period following administration: 14 days - Frequency of observations and weighing: Recorded on day 0 (prior to dosing) 7 and 14. - Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight and gross pathology were examined. 2. not specified

Statistics:

1. No data available 2. not specified

Preliminary study:

1. No data available 2. not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

1. No mortality was observed during the entire experimental period in treated female rats. 2. No mortality was observed at 10000 mg/kg bw

Clinical signs:

1. No clinical sign of toxicity was observed in 300 and 2000 mg/kg bw treated female rats. 2. not specified

Body weight:

1. Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 300 and 2000 mg/kg bw treated female rats. 2. not specified

Gross pathology:

1. No external and Internal gross pathological abnormalities were observed in 300 and 2000 mg/kg bw treated female rats. 2. not specified

Other findings:

1. No data available 2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation the test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl] oxy]ethyl]-N,N-dimethyl- & chloride cannot be classified for acute oral toxicity, as the LD50 value is >2000 mg/kg bw.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride. The studies are as mentioned below:

1. The acute oral toxicity study of test chemical was conducted according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in 12 Wistar female rats at the concentration of 300 and 2000 mg/kg bw and administered via oral gavage route. The given test chemical (100% pure) dissolved as a homogenous suspension in corn oil and hence, it was selected as a vehicle. The desired quantity of the test item (300 mg and 2000 mg) was added to the mortar and triturated using pestle. The vehicle (corn oil) was added to the mortar slowly and mixed well. The formulation was then transferred to a calibrated measuring cylinder. The stock concentration of 200 mg/ml and 30 mg/ml was achieved by making up the volume to 10 ml in the measuring cylinder. The animals were observed for mortality and clinical signs on day 0 (prior to dosing) 7 and 14. Necropsy was performed.No mortality was observed during the entire experimental period in treated female rats.No clinical sign of toxicity was observed in 300 and 2000 mg/kg bw treated female rats.Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 300 and 2000 mg/kg bw treated female rats.No external and internal gross pathological abnormalities were observed in 300 and 2000 mg/kg bw treated female rats. Therefore, the acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when Wistar female rats were treated with test chemical via oral gavage route. Thus, comparing this value with the criteria of CLP regulation, given test chemical cannot be classified for acute oral toxicity.

2. The acute oral toxicity of test chemical was tested in rats at the dose concentration of 10000 mg/kg bw. No mortality was observed. Hence, LD50 value was considered to be >10000 mg/kg bw, when rats were treated with test chemical via oral route.

Thus, based on the above summarised studies, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride cannot be classified for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from database.

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 of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally and functionally similar read across 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 dermal toxicity studies as - WoE-2 and WoE-3. 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

Specific details on test material used for the study:

- Name of test material : Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride- Molecular formula : C35H46ClN5O4- Molecular weight : 636.232 g/mol- Smiles notation : C(CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O)[N+](C)(C)CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O.[ClH-]- InChl : 1S/C35H46N5O4.ClH/c1-7-38(8-2)32-16-12-28(13-17-32)24-30(26-36)34(41)43-22-11-20-40(5,6)21-23-44-35(42)31(27-37)25-29-14-18-33(19-15-29)39(9-3)10-4;/h12-19,24-25H,7-11,20-23H2,1-6H3;1H/q+1;/p-1/b30-24+,31-25+;- Substance type: Organic- Physical state: Liquid

Species:

rat

Strain:

other: 1. Sprague-Dawley 2. Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS- Source: National Institute of Biosciences, Pune.- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.- Weight at study initiation: The weight range of approximately 215.0 to 254.3 grams at initiation of dosing. Body weights at the start : Male Mean: 246.28 g (= 100 %); Minimum : 240.9 g (- 2.18 %); Maximum : 254.3 g (+ 3.26 %)Female Mean: 219.02 g (= 100 %); Minimum : 215.0 g (- 1.84 %); Maximum : 223.4 g (+ 2.00 %)- Identification: Each rat was individually identified by the cage number.- Fasting period before study: No data available- 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): 19.6 to 21.6 degree centigrade.- Humidity (%): 55.0% to 58.4%.- 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: 12-06-2017 to 27-06-20172. TEST ANIMALS- Source: In-House Bred at sa-FORD, Animal Facility (CPCSEA Registration No. 1256/bc/09/CPCSEA)- Weight at study initiation: Male:Minimum: 240 g and Maximum: 280 g , Female:Minimum: 222 g and Maximum: 239 g - Housing: Animals were housed three per polycarbonate cage of size 37 [cm] x 21 [cm], height 20 [cm] and identified by toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start date, dosing date and completion date.- Diet (e.g. ad libitum): conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No: 040316., ad libitum - Water (e.g. ad libitum): Aqua guard filtered tap water, ad libitum - Acclimation period:7 days ENVIRONMENTAL CONDITIONS- Temperature (°C):Minimum: 19.80 °C - Maximum: 22.80 °C- Humidity (%):Minimum: 47.10% - Maximum: 68.60%- Air changes (per hr):12 hour light and 12 hour dark- Photoperiod (hrs dark / hrs light):More than 12 changes per hour IN-LIFE DATES: From: April 19, 2016 To:May 03, 2016

Type of coverage:

other: 1. semiocclusive 2. occlusive

Vehicle:

other: 1. water 2. distilled water

Details on dermal exposure:

1. TEST SITE - Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area) - % coverage: Approximately 10% of the 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: Yes2. TEST SITE - Area of exposure: the fur of dorsal area of the trunk - % coverage: greater than 10% body surface area - Type of wrap if used: Test item was held in contact with the skin with a porous gauze dressing (Approx. 10% of body surface area of rat) and non-irritating tape throughout a 24-hour exposure period. It was ensured that the animals cannot ingest the test item. REMOVAL OF TEST SUBSTANCE - Washing (if done): At the end of the exposure period, 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): The test item was applied uniformly over clipped dorsal area of rat skin. - Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water. VEHICLE - Amount(s) applied (volume or weight with unit): 0.2 ml distilled water

Duration of exposure:

1. 24 hours2. 24-hour

Doses:

1. 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).2. 2000 mg/kg body weight

No. of animals per sex per dose:

1. 10 (5/sex). 2. 5 amle, 5 femlae

Control animals:

not specified

Details on study design:

1. - 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.2. Details on study design- Duration of observation period following administration: 14 days (or other?): 14 day observation period - Frequency of observations and weighing:: at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing) and once a day during the 14 day observation period. - Necropsy of survivors performed: yes - Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Yes

Statistics:

1. not specified2. No statistical analysis was performed since the study was terminated with limit test

Preliminary study:

1. not specified2. 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.

Remarks on result:

other: No mortality was observed

Mortality:

1. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.2. No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period

Clinical signs:

1. 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 result in any signs of toxicity during the study period of 14 days. 2. No systemic signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period No local signs of toxicity (e.g.: Abrasion, Alopecia, Erythema, Oedema, Scale Formation etc.) were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period

Body weight:

1. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.10% and 17.97% respectively. Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.25% and 9.81% respectively. 2. Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0

Gross pathology:

1. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.2. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Other findings:

1. - Other observations: Evaluation of Dermal ReactionSex : 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. 2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation the test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen -1-yl]oxy]ethyl]-N,N-dimethyl- & chloride cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride. The studies are as mentioned below:

1. The study was designed and conducted to determine the acute dermal toxicity profile of 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 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”.

2. The acute dermal toxicity profile of test chemical in 10 male and female Wistar rats according to OECD Guideline 402 (Acute Dermal Toxicity) at the concentration of 2000 mg/kg bw. The given test chemical (100% pure) was moistened with 0.2 ml distilled water and applied by single dermal application on intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1, 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs/Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period.No systemic signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period. No local signs of toxicity (e.g.: Abrasion, Alopecia, Erythema, Oedema, Scale Formation etc.) were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period. Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Therefore, the acute dermal toxicity dose (LD50) was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with test chemical by dermal application over the clipped dorsal area of rat skin. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute dermal toxicity.

Thus, based on the above summarised studies, Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride 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 study report.

Additional information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride. The studies are as mentioned below:

1. The acute oral toxicity study of test chemical was conducted according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in 12 Wistar female rats at the concentration of 300 and 2000 mg/kg bw and administered via oral gavage route. The given test chemical (100% pure) dissolved as a homogenous suspension in corn oil and hence, it was selected as a vehicle. The desired quantity of the test item (300 mg and 2000 mg) was added to the mortar and triturated using pestle. The vehicle (corn oil) was added to the mortar slowly and mixed well. The formulation was then transferred to a calibrated measuring cylinder. The stock concentration of 200 mg/ml and 30 mg/ml was achieved by making up the volume to 10 ml in the measuring cylinder. The animals were observed for mortality and clinical signs on day 0 (prior to dosing) 7 and 14. Necropsy was performed.No mortality was observed during the entire experimental period in treated female rats.No clinical sign of toxicity was observed in 300 and 2000 mg/kg bw treated female rats.Gain in body weight were observed on day 7 and 14, as compared to day 0 body weight, weighed prior to dosing in 300 and 2000 mg/kg bw treated female rats.No external and internal gross pathological abnormalities were observed in 300 and 2000 mg/kg bw treated female rats. Therefore, the acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when Wistar female rats were treated with test chemical via oral gavage route. Thus, comparing this value with the criteria of CLP regulation, given test chemical cannot be classified for acute oral toxicity.

2. The acute oral toxicity of test chemical was tested in rats at the dose concentration of 10000 mg/kg bw. No mortality was observed. Hence, LD50 value was considered to be >10000 mg/kg bw, when rats were treated with test chemical via oral route.

Thus, based on the above summarised studies, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride has very low vapour pressure (1.23E-19 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride. The studies are as mentioned below:

1. The study was designed and conducted to determine the acute dermal toxicity profile of 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 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”.

2. The acute dermal toxicity profile of test chemical in 10 male and female Wistar rats according to OECD Guideline 402 (Acute Dermal Toxicity) at the concentration of 2000 mg/kg bw. The given test chemical (100% pure) was moistened with 0.2 ml distilled water and applied by single dermal application on intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1, 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs/Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period.No systemic signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period. No local signs of toxicity (e.g.: Abrasion, Alopecia, Erythema, Oedema, Scale Formation etc.) were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period. Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Therefore, the acute dermal toxicity dose (LD50) was considered to be >2000 mg/kg bw, when male and female Wistar rats were treated with test chemical by dermal application over the clipped dorsal area of rat skin. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute dermal toxicity.

Thus, based on the above summarised studies, Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 1-​Propanaminium, 3-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​-​N-​[2-​[[2-​cyano-​3-​[4-​(diethylamino)​phenyl]​-​1-​oxo-​2-​propen-​1-​yl]​oxy]​ethyl]​-​N,​N-​dimethyl-​ & chloride cannot be classified for acute oral and dermal toxicity. For acute inhalation toxicity wavier were added so, not possible to classify.