Methanone, 1,1'-(1,4-phenylene)bis[1-(4-phenoxyphenyl)-

Endpoint summary

Description of key information

Acute oral Toxicity: 

The acute oral toxicity dose (LD50) for target chemical 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) was estimated based on QSAR prediction done using the Danish (Q)SAR Database. The LD50 value was estimated to be 1500 mg/kg bw in rats. The study concluded that the LD50 value is between 300-2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified in “Category 4” for acute oral toxicity. 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test substance 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1), which is reported to be 6.37E-14 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Acute dermal Toxicity: 

The acute dermal toxicity dose (LD50) for target chemical 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value was considered to be >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] 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:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Data is from Danish QSAR.

Qualifier:

according to guideline

Guideline:

other: Predicted data

Principles of method if other than guideline:

Prediction is done by using Danish QSAR

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]
- InChI: 1S/C32H22O4/c33-31(25-15-19-29(20-16-25)35-27-7-3-1-4-8-27)23-11-13-24(14-12-23)32(34)26-17-21-30(22-18-26)36-28-9-5-2-6-10-28/h1-22H
- Smiles: c1ccc(cc1)Oc2ccc(cc2)C(=O)c3ccc(cc3)C(=O)c4ccc(cc4)Oc5ccccc5
- Molecular formula:C32H22O4
- Molecular weight :470.5218 g/mole
- Substance type:Organic

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

1500 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 1500 mg/kg bw, when rats were treated with 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) via oral route.

Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1). The LD50 was estimated to be 1500 mg/kg bw with Reliability Index 0.51 (0.5-0.75 = moderate prediction quality), when rats were treated with 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) via oral route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 500 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Danish QSAR.

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 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 two 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:

- IUPAC Name: 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]
- InChI: 1S/C32H22O4/c33-31(25-15-19-29(20-16-25)35-27-7-3-1-4-8-27)23-11-13-24(14-12-23)32(34)26-17-21-30(22-18-26)36-28-9-5-2-6-10-28/h1-22H
- Smiles: c1ccc(cc1)Oc2ccc(cc2)C(=O)c3ccc(cc3)C(=O)c4ccc(cc4)Oc5ccccc5
- Molecular formula :C32H22O4
- Molecular weight:470.5218 g/mole
- Substance type:Organic

Species:

other: 1. rat 2. rabbit

Strain:

other: 1. Sprague-Dawley 2. not specified

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 223.3 to 258.7 grams at initiation of dosing.
Body weights at the start : Male Mean : 256.06 g (= 100 %); Minimum : 252.7 g (- 1.31 %); Maximum : 258.7 g (+ 1.03 %)
Female Mean: 227.60 g (= 100 %); Minimum : 223.3 g (- 1.89 %); Maximum : 231.4 g (+ 1.67 %)
- 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): 20.1 to 22.5 degree centigrade.
- Humidity (%): 56.3% to 58.8%
- 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: 08-06-2017 to 23-06-2017
2. not specified

Type of coverage:

other: 1. semiocclusive 2. Dermal

Vehicle:

other: 1. water 2. not specified

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: Yes
2. not specified

Duration of exposure:

1. 24 hours
2. not specified

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. 5000 mg/kg bw

No. of animals per sex per dose:

1. 10 (5/sex).
2. not specified

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. not specified

Statistics:

1. not specified
2. not specified

Preliminary study:

1. not specified
2. 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 wasw observed

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 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 5000 mg/kg bw

Clinical signs:

other: 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 resul

Gross pathology:

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

Other findings:

1. - 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.
2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation, the test chemical 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) 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 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1). The studies are as mentioned below:

1. The acute dermal toxicity profile of given test chemical was conducted in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity). Distilled water was used as vehicle. 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 given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight.

2. Acute dermal toxicity study of the given test chemical was conducted in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) 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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] 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: 

In different studies, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] along with the data available for the structurally and functionally similar read across chemicals. The predicted data using Danish (Q)SAR Database has also been compared with the experimental study. The studies are summarized as below –

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1). The LD50 was estimated to be 1500 mg/kg bw with Reliability Index 0.51 (0.5-0.75 = moderate prediction quality), when rats were treated with 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) via oral route.

The above prediction study is supported with the data available for the structurally and functionally similar read across chemical and mentioned in authoritative database. The acute oral toxicity study of test chemical was conducted in rats at the dose concentration of 1340 mg/kg bw. Animals were observed for clinical signs. 50% mortality was observed in treated rats. Changes in liver were observed. Hence, LD50 value was considered to be 1340 mg/kg bw, when rats were treated with test chemical via oral route.

These studies are further supported with data available for the structurally and functionally similar read across chemical. The acute oral toxicity study of test chemical was conducted in rats at the dose concentration of 1400 mg/kg bw. 50% mortality was observed in treated rats. Hence, LD50 value was considered to be 1400 mg/kg bw, when rats were treated with test chemical via oral route.

Thus, based on the above summarised studies, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified in “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test substance 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1), which is reported to be 6.37E-14 mmHg. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.

Acute dermal Toxicity: 

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1). The studies are as mentioned below:

1. The acute dermal toxicity profile of given test chemical was conducted in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity). Distilled water was used as vehicle. 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 given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight.

2. Acute dermal toxicity study of the given test chemical was conducted in rabbits at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) 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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] (CAS no.: 54299-17-1) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity and LD50 value is >2000 mg/kg bw for acute dermal toxicity. Thus, comparing these values with the criteria of CLP regulation, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified in “Category 4” for acute oral toxicity and cannot be classified for acute dermal toxicity. For acute inhalation toxicity wavier were added so, not possible to classify.