Benzimidazole

Endpoint summary

Description of key information

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Benzimidazole (CAS No: 51-17-2). The studies are as mentioned below:

 

The skin sensitization study was conducted by Magnusson and Kligman method in Dunkin Hartley guinea pig for read across chemical. In test group 20 animals were as in negative control 10 animals were used. In induction phase,1stapplication by intradermal injections of 0.1ml Freund’s complete adjuvant in water, test material 1% w/v in arachis oil, and Freund’s + test material 1% w/v in arachis oil (1:1) was given at 3 different site. The 2ndinduction application given after 1 week as a single occlusive patch of0.2-0.3ml of test material 50% w/w in arachis oil for 48hr .The challenge was given on 21 day after 1stinduction application with concentration 0.1-0.2ml of test material 25 and 10w/w in arachis oil. No reaction were observed in any animals, hence it is considered that the test chemical was not skin sensitizing in guinea pig.

 

The above result was further supported by a close patch repeated insult dermal sensitization study (modified Buehler test) performed in Hartley albino guinea pig using 5 male and 5 female for another read across chemical. The hair was clipped short before induction and challenge application in each animal. In induction phase test material and positive control agent in 0.3ml volume was applied directly on to the test site and covered with patch (hilltop chamber) and then with by impermeable plastic covered by elastic adhesive bandage for 6hr, extra material form test site was removed. Total 3 exposures were given in a week. After that challenge application was performed in same manner. The chemical 1-chloro-2, 4-dinitro benzene was used as positive control. No sensitization was observed in any treated animal .Hence the test chemical was considered as not skin sensitizing on guinea pigs.

 

 Based on the above summarized studies for target chemical Benzimidazole (CAS No: 51-17-2) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it 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:

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 2 skin sensitization studies as- WoE-2 and WoE-3.
Skin sensitization of test chemical was determined by performing tests on guinea pigs.

GLP compliance:

not specified

Type of study:

other: 1.guinea pig maximisation test 2.

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name of test material: Benzimidazole
Molecular formula: C7H6N2
Molecular weight: 118.1384 g/mol
Smiles notation: c12c(nc[nH]1)cccc2
InChl: 1S/C7H6N2/c12476(31)8597/h15H,(H,8,9)
Substance Type: Organic
Physical State: Solid

Species:

guinea pig

Strain:

other: 1.Dunkin-Hartley 2.Hartley

Sex:

male

Details on test animals and environmental conditions:

1.not specified
2.Details on test animal
TEST ANIMALS
- Source: Hazelcon-dutchland laboratory animals Denver.PA.
- Age at study initiation: No data available

- Weight at study initiation:301-384g
- Housing: No data available

- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: No data available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available

- Humidity (%):No data available

- Air changes (per hr): No data available

- Photoperiod (hrs dark / hrs light): No data available


IN-LIFE DATES: From: To: No data available

Route:

other: 1.intradermal and epicutaneous

Vehicle:

arachis oil

Concentration / amount:

For intradermal injection 1%w/v
For topical application -0.2-0.3ml of test material 50% w/w in arachis oil

Day(s)/duration:

48hr

Adequacy of induction:

not specified

Route:

other: 2.epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

0.3ml

Day(s)/duration:

6 hour

Adequacy of induction:

not specified

No.:

#1

Route:

other: 2.epicutaneous, occlusive

Vehicle:

arachis oil

Concentration / amount:

0.1-0.2ml test material 25 and 10 w/w in arachis oil

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No.:

#1

Route:

other: 2.epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

0.3mL

Day(s)/duration:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

1. Total :30
Test:20
Negative control:10

2.Total :10
Male :5
Female: 5

Details on study design:

1.MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:2
- Exposure period:48hr
- Test groups:20
- Control group: No data available

- Site: 3 separate site

- Frequency of applications: on 1st day and after 1 week

- Duration: 1week
- Concentrations: For intradermal injection : 1%w/v in arachis oil
For topical application :0.2-0.3ml of test material 50% w/w in arachis oil
OTHER: intradermal injections of 0.1ml Freund’s complete adjuvant in water, test material 1% w/v in arachis oil, and Freund’s + test material 1% w/v in arachis oil (1:1)

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: After 20 days
- Exposure period: No data available
- Test groups: 20
- Control group: No data available
- Site: No data available

- Concentrations: 0.1-0.2ml of test material 25 and 10 w/w in arachis oil
- Evaluation (hr after challenge): No data available

2.A. INDUCTION EXPOSURE
- No. of exposures:3
- Exposure period:6hr
- Test groups:10
- Control group: No data available

- Site: No data available

- Frequency of applications: No data available

- Duration: 1week
- Concentrations:0.3ml

CHALLENGE EXPOSURE
- No. of exposures: No data available

- Day(s) of challenge: No data available
- Exposure period: No data available
- Test groups: 10
- Control group: No data available

- Site: No data available

- Concentrations: 0.3ml
- Evaluation (hr after challenge): No data available

Challenge controls:

No data available.

Positive control substance(s):

yes

Remarks:

2.1-chloro-2,4-dinitro benzene

Reading:

other: 1.1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1-0.2ml of test material 25 and 10 w/w in arachis oil

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No sensitization reaction was observed

Remarks on result:

no indication of skin sensitisation

Reading:

other: 2.1st reading

Group:

test chemical

Dose level:

0.3ml

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization reaction was observed

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No sensitization reaction was observed

Interpretation of results:

other: not sensitizing

Conclusions:

The test material Benzimidazole (CAS No: 51-17-2) was considered to be not sensitizing to the skin of guinea pigs.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Benzimidazole (CAS No: 51-17-2). The studies are as mentioned below:

 

The skin sensitization study was conducted by Magnusson and Kligman method in Dunkin Hartley guinea pig for read across chemical. In test group 20 animals were as in negative control 10 animals were used. In induction phase,1stapplication by intradermal injections of 0.1ml Freund’s complete adjuvant in water, test material 1% w/v in arachis oil, and Freund’s + test material 1% w/v in arachis oil (1:1) was given at 3 different site. The 2ndinduction application given after 1 week as a single occlusive patch of0.2-0.3ml of test material 50% w/w in arachis oil for 48hr .The challenge was given on 21 day after 1stinduction application with concentration 0.1-0.2ml of test material 25 and 10w/w in arachis oil. No reaction were observed in any animals, hence it is considered that the test chemical was not skin sensitizing in guinea pig.

 

The above result was further supported by a close patch repeated insult dermal sensitization study (modified Buehler test) performed in Hartley albino guinea pig using 5 male and 5 female for another read across chemical. The hair was clipped short before induction and challenge application in each animal. In induction phase test material and positive control agent in 0.3ml volume was applied directly on to the test site and covered with patch (hilltop chamber) and then with by impermeable plastic covered by elastic adhesive bandage for 6hr, extra material form test site was removed. Total 3 exposures were given in a week. After that challenge application was performed in same manner. The chemical 1-chloro-2, 4-dinitro benzene was used as positive control. No sensitization was observed in any treated animal .Hence the test chemical was considered as not skin sensitizing on guinea pigs.

 

 Based on the above summarized studies for target chemical Benzimidazole (CAS No: 51-17-2) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Benzimidazole (CAS No: 51-17-2). The studies are as mentioned below:

 

The skin sensitization study was conducted by Magnusson and Kligman method in Dunkin Hartley guinea pig for read across chemical. In test group 20 animals were as in negative control 10 animals were used. In induction phase,1stapplication by intradermal injections of 0.1ml Freund’s complete adjuvant in water, test material 1% w/v in arachis oil, and Freund’s + test material 1% w/v in arachis oil (1:1) was given at 3 different site. The 2ndinduction application given after 1 week as a single occlusive patch of0.2-0.3ml of test material 50% w/w in arachis oil for 48hr .The challenge was given on 21 day after 1stinduction application with concentration 0.1-0.2ml of test material 25 and 10w/w in arachis oil. No reaction were observed in any animals, hence it is considered that the test chemical was not skin sensitizing in guinea pig.

 

The above result was further supported by a close patch repeated insult dermal sensitization study (modified Buehler test) performed in Hartley albino guinea pig using 5 male and 5 female for another read across chemical. The hair was clipped short before induction and challenge application in each animal. In induction phase test material and positive control agent in 0.3ml volume was applied directly on to the test site and covered with patch (hilltop chamber) and then with by impermeable plastic covered by elastic adhesive bandage for 6hr, extra material form test site was removed. Total 3 exposures were given in a week. After that challenge application was performed in same manner. The chemical 1-chloro-2, 4-dinitro benzene was used as positive control. No sensitization was observed in any treated animal .Hence the test chemical was considered as not skin sensitizing on guinea pigs.

 

 Based on the above summarized studies for target chemical Benzimidazole (CAS No: 51-17-2) and its structurally and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance Benzimidazole (CAS No: 51-17-2) and its structurally and functionally similar read across substanceswere observed in various studies. From the results obtained from these studies it is concluded that the chemical Benzimidazole (CAS No: 51-17-2) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.