Methyl 5-nitrohydrogen.isophthalate

Endpoint summary

Description of key information

Eventhough the estimated result for the test chemical indicates that the test chemical has the potential to cause sensitization to skin, but the remaining experimental results suggest otherwise. Therefore by applying the weight of evidence approach, the test chemical can be estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be considered to be “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:

data from handbook or collection of data

Remarks:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals. The study 2,3,4 are referred to as study 1,2,3

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach based on various test chemicals

Justification for non-LLNA method:

not specified

Species:

other: humans

Strain:

not specified

Sex:

not specified

Route:

other: not specified

Vehicle:

not specified

Adequacy of induction:

not specified

Route:

intradermal and epicutaneous

Vehicle:

other: acetone-polyethylene glycol 400 (70:30, v/v)].

Concentration / amount:

Intradermal- 1.0%
EPicutaneous, occlusive

Day(s)/duration:

48 h

Adequacy of induction:

other: Preliminary irritation tests were carried out to determine the concentrations of the test substances suitable for induction of sensitization and for sensitization challenge.

Route:

epicutaneous, occlusive

Vehicle:

other:

Concentration / amount:

3ml of a 30% (w/w) solution in dimethylsulfoxide (DMSO

Adequacy of induction:

not specified

No.:

#1

Route:

other: not applicable

Vehicle:

not specified

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: acetone-polyethylene glycol 400 (70:30, v/v)].

Concentration / amount:

10% in acetone-polyethylene glycol 400 (70:30, v/v)].

Day(s)/duration:

24 hours

Adequacy of challenge:

other: maximum non irritant concentration of test chemical

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

DMSO

Concentration / amount:

0.3 ml of a 70% (w/w) aqueous DMSO solution.

Adequacy of challenge:

not specified

No. of animals per dose:

1. no data available
2. 6+
10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

Eventhough the estimated result for the test chemical indicates that the test chemical has the potential to cause sensitization to skin, but the remaining experimental results suggest otherwise. Therefore by applying the weight of evidence approach, the test chemical can be estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be considered to be “Not Classified”.

Executive summary:

Various studies have been reviewed to determine the degree of dermal sensitization caused by the test chemical in living organisms. These include in vivo experimental studies along with the estimated data for the test chemicals. The results are summarized below:

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, positive skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be sensitizing.

The Magnusson and Kligman guinea-pig maximization test was performed to determine the dermal sensitization potential of the test chemical.

Preliminary irritation tests were carried out to determine the concentrations of the test substances suitable for induction of sensitization and for sensitization challenge. Albino Dunkin- Hartley guinea-pigs weighing approximately 350 g at the start of the study.

Guinea-pigs were treated by a series of six intradermal injections[1.0%] in the shoulder region to induce sensitization. After 6-8 days, sensitization was boosted by a 48-hr occluded patch [25.0% in acetone-polyethylene glycol 400 (70:30, v/v)] placed over the injection site. After a rest period of 12-14 days, the animals were challenged on one flank by a 24-hr occluded patch at the maximum non-irritant concentration [10% inacetone-polyethylene glycol 400 (70:30, v/v)].

Challenge sites were scored for erythema (scale 0-3) and oedema 24 and 48 hr after removal of the patches.

No dermal reactions were observed in the induction and challenge phase. Hence the test chemical was considered to be not sensitizing to skin.

These results are further supported by a Buehler Test conducted on ten male guinea pigs for chemical to assess its skin sensitization potential. 

The test chemical was applied once a week at a dose of 0.3ml of a 30% (w/w) solution in dimethylsulfoxide (DMSO) to the shaved backs of ten male guinea pigs during an induction period of three weeks. Another group of 10 male guinea pigs served as a vehicle control and was similarly dosed with 0.3ml of undiluted DMSO. A third group of ten sham control guinea pigs was handled in the same manner, but was not treated with test article or vehicle. Two weeks following application of the third induction dose, the treated andsham control guinea pigs each received a challenge dose of 0.3 ml of the 30% test article/DMSO solution; the vehicle control guinea pigs each received a challenge dose of 0.3 ml of a 70% (w/w) aqueous DMSO solution. All guinea pigs were scored for erythema approximately 24 and 48 hours following application of the first induction dose and the challenge dose.

Positive erythema reactions (i.e., a score >= 2) were observed in only one test article–treated guinea pig, compared to no vehicle or sham control guinea pigs during the challenge phase. 

Since no sensitization reactions were observed in majority of treated animals, the chemical was considered as not sensitizing to the skin of guinea pigs.

Eventhough the estimated result for the test chemical indicates that the test chemical has the potential to cause sensitization to skin, but the remaining experimental results suggest otherwise. Therefore by applying the weight of evidence approach, the test chemical can be estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be considered to be “Not Classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies have been reviewed to determine the degree of dermal sensitization caused by the test chemical in living organisms. These include in vivo experimental studies along with the estimated data for the test chemicals. The results are summarized below:

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, positive skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be sensitizing.

The Magnusson and Kligman guinea-pig maximization test was performed to determine the dermal sensitization potential of the test chemical.

Preliminary irritation tests were carried out to determine the concentrations of the test substances suitable for induction of sensitization and for sensitization challenge. Albino Dunkin- Hartley guinea-pigs weighing approximately 350 g at the start of the study.

Guinea-pigs were treated by a series of six intradermal injections[1.0%] in the shoulder region to induce sensitization. After 6-8 days, sensitization was boosted by a 48-hr occluded patch [25.0% in acetone-polyethylene glycol 400 (70:30, v/v)] placed over the injection site. After a rest period of 12-14 days, the animals were challenged on one flank by a 24-hr occluded patch at the maximum non-irritant concentration [10% inacetone-polyethylene glycol 400 (70:30, v/v)].

Challenge sites were scored for erythema (scale 0-3) and oedema 24 and 48 hr after removal of the patches.

No dermal reactions were observed in the induction and challenge phase. Hence the test chemical was considered to be not sensitizing to skin.

These results are further supported by a Buehler Test conducted on ten male guinea pigs for chemical to assess its skin sensitization potential. 

The test chemical was applied once a week at a dose of 0.3ml of a 30% (w/w) solution in dimethylsulfoxide (DMSO) to the shaved backs of ten male guinea pigs during an induction period of three weeks. Another group of 10 male guinea pigs served as a vehicle control and was similarly dosed with 0.3ml of undiluted DMSO. A third group of ten sham control guinea pigs was handled in the same manner, but was not treated with test article or vehicle. Two weeks following application of the third induction dose, the treated andsham control guinea pigs each received a challenge dose of 0.3 ml of the 30% test article/DMSO solution; the vehicle control guinea pigs each received a challenge dose of 0.3 ml of a 70% (w/w) aqueous DMSO solution. All guinea pigs were scored for erythema approximately 24 and 48 hours following application of the first induction dose and the challenge dose.

Positive erythema reactions (i.e., a score >= 2) were observed in only one test article–treated guinea pig, compared to no vehicle or sham control guinea pigs during the challenge phase. 

Since no sensitization reactions were observed in majority of treated animals, the chemical was considered as not sensitizing to the skin of guinea pigs.

Eventhough the estimated result for the test chemical indicates that the test chemical has the potential to cause sensitization to skin, but the remaining experimental results suggest otherwise. Therefore by applying the weight of evidence approach, the test chemical can be estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be considered to be “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Eventhough the estimated result for the test chemical indicates that the test chemical has the potential to cause sensitization to skin, but the remaining experimental results suggest otherwise. Therefore by applying the weight of evidence approach, the test chemical can be estimated to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be considered to be “Not Classified”.