Registration Dossier

Administrative data

Description of key information

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 1,4 divinyl benzene was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 1,4 divinyl benzene can be classified under the category “Not Classified”. 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
other: Weight of evidence based on similar chemicals
Justification for type of information:
Weight of evidence based on similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weigth of evidence based on similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of 1,4-Diethenylbenzene
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on similar chemicals
Specific details on test material used for the study:
- Name of test material: 1,4-Diethenylbenzene- Molecular formula: C10H10- Molecular weight: 130.189g/mol - Smiles notation: C(c1ccc(cc1)C=C)=C- InChl : 1S/C10H10/c1-3-9-5-7-10(4-2)8-6-9/h3-8H,1-2H2- Substance type: Organic- Physical state: Solid
Species:
other: humans, guinea pigs
Strain:
not specified
Sex:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
2%
Day(s)/duration:
no data available
Adequacy of induction:
not specified
Route:
intradermal
Vehicle:
not specified
Concentration / amount:
0.001 ug/ml
Adequacy of induction:
other: A moderately irritant concentration was selected for the intradermal induction concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
2%
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
0.0026 ug/ml
Day(s)/duration:
6 hours
Adequacy of challenge:
other: maximum non-irritant concentration
No. of animals per dose:
1. no data available2. 253. 10
Details on study design:
The study is based on weight of evidence approach from the read across values
Challenge controls:
no data available
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
No. with + reactions:
0
Clinical observations:
no sensitization reactions observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:
Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 1,4 divinyl benzene was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 1,4 divinyl benzene can be classified under the category “Not Classified”. 
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of 1,4 divinyl benzene.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 1,4 divinyl benzene. Based on estimation, no skin sensitization effects were known when 1,4 divinylbenzene was exposed to skin of humans and guinea pigs.Hence,1,4 divinyl benzene  can be considered not sensitizing to skin.

This is supported by the result of the human maximization test carried out to assess the dermal sensitization potential of the structurally similar read across chemical.

The test chemical 2% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of sensitization (duration of exposure, observation period not mentioned).

No skin sensitization reactions were observed in treated volunteers .Hence the test chemical was considered to be not sensitizing to humans.

These studies are further supported by the results of the Single Injection Adjuvant Test (SIAT) performed to assess the dermal sensitization potential of the structurally similar chemical.

10 guinea pigs were used and were housed in single sex pairs for the duration of the experiment in a room maintained at a constant temperature of 20°C.Tests were carried out on groups of 4 guinea-pigs to select the appropriate concentrations for induction and challenge. A moderately irritant concentration was selected for the intradermal induction concentration and Challenge was made using the maximum non-irritant concentration.

0.001 ug/mlsingle intradermal injection of the test substance in complete FCA was injected in the nuchal region of the test guinea pigs. After a rest period of 12 – 14 days, the guinea pigs were challenged with 0.0026 ug/ml of the test chemical applied on the razored flank of the guinea pigs under occlusion for 6 hours. Groups of 4 untreated control guinea pigs of similiar age and weight to the test guinea pigs were included in this challenge. Reactions were assessed 18 and 42 hours after removal of the chamber, according to the degree of erythema and edema.

The challenge was repeated at weekly intervals (3-4 challenges in total) on opposite flanks using further groups of untreated control guinea pigs at each challenge.

The test chemical failed to induce any signs of dermal sensitization in guinea pigs

Hence, it can be considered to be not sensitizing to guinea pigs.

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 1,4 divinyl benzene was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 1,4 divinyl benzene can be classified under the category “Not Classified”. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of 1,4 divinyl benzene.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 1,4 divinyl benzene. Based on estimation, no skin sensitization effects were known when 1,4 divinylbenzene was exposed to skin of humans and guinea pigs.Hence,1,4 divinyl benzene  can be considered not sensitizing to skin.

This is supported by the result of the human maximization test carried out to assess the dermal sensitization potential of the structurally similar read across chemical.

The test chemical 2% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of sensitization (duration of exposure, observation period not mentioned).

No skin sensitization reactions were observed in treated volunteers .Hence the test chemical was considered to be not sensitizing to humans.

These studies are further supported by the results of the Single Injection Adjuvant Test (SIAT) performed to assess the dermal sensitization potential of the structurally similar chemical.

10 guinea pigs were used and were housed in single sex pairs for the duration of the experiment in a room maintained at a constant temperature of 20°C.Tests were carried out on groups of 4 guinea-pigs to select the appropriate concentrations for induction and challenge. A moderately irritant concentration was selected for the intradermal induction concentration and Challenge was made using the maximum non-irritant concentration.

0.001 ug/mlsingle intradermal injection of the test substance in complete FCA was injected in the nuchal region of the test guinea pigs. After a rest period of 12 – 14 days, the guinea pigs were challenged with 0.0026 ug/ml of the test chemical applied on the razored flank of the guinea pigs under occlusion for 6 hours. Groups of 4 untreated control guinea pigs of similiar age and weight to the test guinea pigs were included in this challenge. Reactions were assessed 18 and 42 hours after removal of the chamber, according to the degree of erythema and edema.

The challenge was repeated at weekly intervals (3-4 challenges in total) on opposite flanks using further groups of untreated control guinea pigs at each challenge.

The test chemical failed to induce any signs of dermal sensitization in guinea pigs

Hence, it can be considered to be not sensitizing to guinea pigs.

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 1,4 divinyl benzene was estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, 1,4 divinyl benzene can be classified under the category “Not Classified”. 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 1,4-Diethenylbenzene can be not sensitizing to skin.

Hence by applying the weight of evidence approach, 1,4-Diethenylbenzene can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.