Registration Dossier

Administrative data

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:
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 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:
not specified
Body weight:
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
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:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
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 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:
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. not specified
Body weight:
1. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 10.03% and 18.99% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.51% and 11.11% respectively.
2. not specified
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
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.