Registration Dossier

Acute oral Toxicity:

The acute oral toxicity dose (LD50) for 1,4-Diethenylbenzene (CAS no.: 105-06-6) was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity dose (LC50) for 1,4-Diethenylbenzene (CAS no.: 105-06-6) was considered based on data available for the structurally and functionally similar read across chemicals. The LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene cannot be classified for acute inhalation toxicity.

Acute dermal Toxicity:

The acute dermal toxicity dose (LD50) for 1,4-Diethenylbenzene (CAS no.: 105-06-6) 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, 1,4-Diethenylbenzene cannot be classified for acute dermal toxicity.

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 two acute oral toxicity studies as- WoE-2 and WoE-3Acute 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:

- IUPAC Name: 1,4-diethenylbenzene- Mol. formula: C10H10- Molecular Weight: 130.189 g/mole- InChI: 1S/C10H10/c1-3-9-5-7-10(4-2)8-6-9/h3-8H,1-2H2- Smiles: C(c1ccc(cc1)C=C)=C- Physical state: solid

Species:

rat

Strain:

other: 1. CD rat 2. not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS- Age at study initiation: 4 week-old- Fasting period before study: fasted overnight2. not specified

Route of administration:

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

Vehicle:

other: 1. corn oil 2. unchanged (no vehicle)

Details on oral exposure:

1. not specified2. not specified

Doses:

1. 700, 1000, 1429, 2014 mg/kg2. 1600 mg/kg

No. of animals per sex per dose:

1. groups of 5 rats of each sex2. Total = 10

Control animals:

not specified

Details on study design:

1. - Duration of observation period following administration: 14 days - Necropsy of survivors performed: yes, survivors were killed and necropsied.- Other examinations performed: Animals were observed for mortality and clinical signs.2. - Duration of observation period following administration: 14 days- Other examinations performed: Animals were observed for mortality and body weight changes.

Statistics:

1. not specified2. not specified

Preliminary study:

1. not specified2. not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 732 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 503 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

2 027 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Based on:

test mat.

Mortality:

1. Mortality occurred within 3 days of administration.2. Mortality was observed with 1 day.

Clinical signs:

1. Clinical signs at dose levels of 1000 mg/kg and above were severe but did not suggest any specific mechanism of toxicity.2. not specified

Body weight:

1. not specified2. Body weight change was observed.

Gross pathology:

1. Necropsy of decedents revealed altered stomach contents and occasionally dark thymus, dark areas on the gastric mucosa and body surface staining.2. not specified

Other findings:

1. not specified2. not specified

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to CLP regulation, the test chemical 1,4-diethenylbenzene (CAS no.: 105-06-6) can be classified as "Category 4" for acute oral toxicity, as the LD50 value is between 300-2000 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 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute oral toxicity study was conducted by using test chemical in groups of 5 CD rats of each sex at the dose concentration of 700, 1000, 1429, 2014 mg/kg bw. The test chemical was dissolved incorn oil and administered via oral gavage route. Animals were observed for mortality and clinical signs for 14 days after administration of the test substance and survivors were killed and necropsied. Decedents were necropsied as soon as possible after death. Mortality occurred within 3 days of administration. Clinical signs at dose levels of 1000 mg/kg and above were severe but did not suggest any specific mechanism of toxicity. Necropsy of decedents revealed altered stomach contents and occasionally dark thymus, dark areas on the gastric mucosa and body surface staining. Hence, LD50 value was considered to be 1732 mg/kg in both male and female; 1503 mg/kg in males; and 2027 mg/kg in females, when groups of 5 CD rats of each sex were treated with test chemical via oral gavage route.

2. Acute oral toxicity study was conducted by using test chemical (Undiluted) in 10 male rats at the dose concentration of 1600 mg/kg. Animals were observed for mortality and body weight changes for 14 days. Mortality was observed with 1 day. Body weight change was observed. Therefore, LD50 value was considered to be 1600 mg/kg bw, when 10 male rats were treated with test chemical via oral route.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene can be classified as “Category 4” for acute oral toxicity.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 732 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 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 two acute inhalation toxicity studies as- WoE-2 and WoE-3Acute 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

Specific details on test material used for the study:

- IUPAC Name: 1,4-diethenylbenzene- Mol. formula: C10H10- Molecular Weight: 130.189 g/mole- InChI: 1S/C10H10/c1-3-9-5-7-10(4-2)8-6-9/h3-8H,1-2H2- Smiles: C(c1ccc(cc1)C=C)=C- Physical state: solid

Species:

other: 1. rat 2. mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

1. not specified2. not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remark on MMAD/GSD:

1. not specified2. not specified

Details on inhalation exposure:

1. not specified2. not specified

Analytical verification of test atmosphere concentrations:

not specified

Remarks on duration:

1. 7 h 2. 4 h

Concentrations:

1. 645 ppm (645000 mg/m3)2. 54000 mg/m3

No. of animals per sex per dose:

1. not specified2. not specified

Control animals:

not specified

Details on study design:

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

Statistics:

1. not specified2. not specified

Preliminary study:

1. not specified2. not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

645 000 mg/m³ air

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: 50% mortality was observed

Sex:

not specified

Dose descriptor:

LC50

Effect level:

54 000 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed

Mortality:

1. 50% mortality was observed at 645000 mg/m32. 50% mortality was observed at 54000 mg/m3

Clinical signs:

other: 1. Toxic effects were not observed.2. not specified

Body weight:

1. not specified2. not specified

Gross pathology:

1. not specified2. not specified

Other findings:

1. not specified2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation, the test chemical 1,4-diethenylbenzene (CAS no.: 105-06-6) cannot be classified for acute inhalation toxicity, as the LC50 value is >5 mg/L.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute inhalation toxicity of the test chemical 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute Inhalation toxicity study was conducted by using test chemical in rats at the concentration of 645 ppm by inhalation route via vapors for 7 hours. Animals were observed for mortality and clinical signs. 50% mortality was observed. Toxic effects were not observed. Hence, LC50 value was considered to be 645 ppm (645000 mg/m3), when rats were exposed with test chemical via inhalation route by vapors for 7 hrs.

2. Acute Inhalation toxicity study was conducted by using test chemical in rats at the concentrations of 54000 mg/m3 by inhalation route via vapors for 4 hours. 50% mortality was observed. Hence, LC50 value was considered to be 54000 mg/m3, when mice were exposed with test chemical via inhalation route by vapors for 4 hrs.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) and it’s structurally and functionally similar read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene cannot be classified for acute inhalation toxicity.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

645 000 mg/m³

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

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 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-diethenylbenzene- Mol. formula: C10H10- Molecular Weight: 130.189 g/mole- InChI: 1S/C10H10/c1-3-9-5-7-10(4-2)8-6-9/h3-8H,1-2H2- Smiles: C(c1ccc(cc1)C=C)=C- Physical state: solid

Species:

other: 1. rat 2. rabbit

Strain:

other: 1. CD rat 2. not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. not specified2. not specified

Type of coverage:

other: 1. occlusive 2. dermal

Vehicle:

other: 1. unchanged (no vehicle) 2. not specified

Details on dermal exposure:

1. TEST SITE - Area of exposure: clipped skin - % coverage: The material was spread over a 5 x 5 cm area - Type of wrap if used: The material was covered with gauss and then an impermeable bandage. REMOVAL OF TEST SUBSTANCE - Washing (if done): The dressing was removed and the remaining material removed with a wet towel. - Time after start of exposure:24 hours 2. not specified

Duration of exposure:

1. 24 hours 2. not specified

Doses:

1. 2000 mg/kg2. 5000 mg/kg bw

No. of animals per sex per dose:

1. groups of 5 rats of each sex2. Total = 4 rabbits

Control animals:

not specified

Details on study design:

1. - Duration of observation period following administration: 14 days - Necropsy of survivors performed: yes, animals were sacrificed on the 14th day after removal of the test substance, and submitted to a necropsy for detection of possible macroscopic effects on the major organs.- Other examinations performed: Animals were observed for mortality, clinical signs and body weight changes.2. Details on study design:- Other examinations performed: Animals were observed for mortality and clinical signs

Statistics:

1. not specified2. not specified

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:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

1. No mortality was observed at 2000 mg/kg bw.2. 1/4 animal died at 5000 mg/kg bw.

Clinical signs:

1. No adverse clinical signs were reported and the application site was free of local irritation throughout the 14 day observation period. 2. No clinical signs were reported other than skin irritation which was graded as slight to moderate redness and moderate edema.

Body weight:

1. Animals gained bodyweight normally.2. not specified

Gross pathology:

1. All organs appeared normal on necropsy.2. not specified

Other findings:

1. not specified2. not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation the test chemical 1,4-diethenylbenzene (CAS no.: 105-06-6) cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw

Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute dermal toxicity study was conducted by using test chemical in groups of 5 CD rats of each sex at the dose concentration of 2000 mg/kg bw. The material (neat) was spread over a 5 x 5 cm area of clipped skin and covered with gauss and then an impermeable bandage. The material was left on the skin for 24 hours after which the dressing was removed and the remaining material removed with a wet towel. Animals were observed for 14 days after removal of the dressing, were sacrificed on the 14thday after removal of the test substance, and submitted to a necropsy for detection of possible macroscopic effects on the major organs. No mortality was observed at 2000 mg/kg bw. No adverse clinical signs were reported and the application site was free of local irritation throughout the 14 day observation period. Animals gained bodyweight normally. All organs appeared normal on necropsy. Hence, LD50 value was considered to be >2000 mg/kg bw, when groups of 5 CD rats of each sex were treated with test chemical by dermal application occlusively.

2. Acute dermal toxicity study was conducted in 4 rabbits at the dose concentration of 5000 mg/kg bw by dermal application. Animals were observed for mortality and clinical signs. 1/4 animal died at 5000 mg/kg bw. No clinical signs were reported other than skin irritation which was graded as slight to moderate redness and moderate edema. Therefore, LD50 value was considered to be >5000 mg/kg bw, when 4 rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) 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-Diethenylbenzene cannot be classified for acute dermal toxicity.

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 peer-reviewed journal.

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 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute oral toxicity study was conducted by using test chemical in groups of 5 CD rats of each sex at the dose concentration of 700, 1000, 1429, 2014 mg/kg bw. The test chemical was dissolved incorn oil and administered via oral gavage route. Animals were observed for mortality and clinical signs for 14 days after administration of the test substance and survivors were killed and necropsied. Decedents were necropsied as soon as possible after death. Mortality occurred within 3 days of administration. Clinical signs at dose levels of 1000 mg/kg and above were severe but did not suggest any specific mechanism of toxicity. Necropsy of decedents revealed altered stomach contents and occasionally dark thymus, dark areas on the gastric mucosa and body surface staining. Hence, LD50 value was considered to be 1732 mg/kg in both male and female; 1503 mg/kg in males; and 2027 mg/kg in females, when groups of 5 CD rats of each sex were treated with test chemical via oral gavage route.

2. Acute oral toxicity study was conducted by using test chemical (Undiluted) in 10 male rats at the dose concentration of 1600 mg/kg. Animals were observed for mortality and body weight changes for 14 days. Mortality was observed with 1 day. Body weight change was observed. Therefore, LD50 value was considered to be 1600 mg/kg bw, when 10 male rats were treated with test chemical via oral route.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute inhalation toxicity of the test chemical 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute Inhalation toxicity study was conducted by using test chemical in rats at the concentration of 645 ppm by inhalation route via vapors for 7 hours. Animals were observed for mortality and clinical signs. 50% mortality was observed. Toxic effects were not observed. Hence, LC50 value was considered to be 645 ppm (645000 mg/m3), when rats were exposed with test chemical via inhalation route by vapors for 7 hrs.

2. Acute Inhalation toxicity study was conducted by using test chemical in rats at the concentrations of 54000 mg/m3 by inhalation route via vapors for 4 hours. 50% mortality was observed. Hence, LC50 value was considered to be 54000 mg/m3, when mice were exposed with test chemical via inhalation route by vapors for 4 hrs.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) and it’s structurally and functionally similar read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1,4-Diethenylbenzene cannot be classified for acute inhalation toxicity.

Acute dermal Toxicity:

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical 1,4-Diethenylbenzene (CAS no.: 105-06-6). The studies are as mentioned below:

1. Acute dermal toxicity study was conducted by using test chemical in groups of 5 CD rats of each sex at the dose concentration of 2000 mg/kg bw. The material (neat) was spread over a 5 x 5 cm area of clipped skin and covered with gauss and then an impermeable bandage. The material was left on the skin for 24 hours after which the dressing was removed and the remaining material removed with a wet towel. Animals were observed for 14 days after removal of the dressing, were sacrificed on the 14thday after removal of the test substance, and submitted to a necropsy for detection of possible macroscopic effects on the major organs. No mortality was observed at 2000 mg/kg bw. No adverse clinical signs were reported and the application site was free of local irritation throughout the 14 day observation period. Animals gained bodyweight normally. All organs appeared normal on necropsy. Hence, LD50 value was considered to be >2000 mg/kg bw, when groups of 5 CD rats of each sex were treated with test chemical by dermal application occlusively.

2. Acute dermal toxicity study was conducted in 4 rabbits at the dose concentration of 5000 mg/kg bw by dermal application. Animals were observed for mortality and clinical signs. 1/4 animal died at 5000 mg/kg bw. No clinical signs were reported other than skin irritation which was graded as slight to moderate redness and moderate edema. Therefore, LD50 value was considered to be >5000 mg/kg bw, when 4 rabbits were treated with test chemical by dermal application.

Thus, based on the above summarised studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) 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-Diethenylbenzene cannot be classified for acute dermal toxicity.

Based on the above studies, 1,4-Diethenylbenzene (CAS no.: 105-06-6) 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; LC50 value is >5 mg/L for acute inhalation 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-Diethenylbenzene can be classified as “Category 4” for acute oral toxicity and cannot be classified for acute dermal and inhalation toxicity.