2-methyl-m-phenylene diisocyanate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from publication

Data source

Reference

Reference Type:

publication

Title:

Concentration-Dependent Elicitation of Dermal Sensitization in Guinea Pigs Treated with 2,4-Toluene Diisocyanate

Author:

FRANCIS J. KOSCHIER, EDWARD J. BURDEN, CINDY S. BRUNKHORST, AND MARVIN A. FRIEDMAN

Year:

1983

Bibliographic source:

TOXICOLCCY AND APPLIED PHARMACOLOGY 67,401-407 (1983)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

An open epicutaneous test was performed on guinea pigs to evaluate the significance of dermal hypersensitization of 2, 4-Toluene diisocyanate (TDI).

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,4-Toluene diisocyanate

IUPAC Name:

2,4-Toluene diisocyanate

Constituent 2

Reference substance name:

4-methyl-m-phenylene diisocyanate

EC Number:

209-544-5

EC Name:

4-methyl-m-phenylene diisocyanate

Cas Number:

584-84-9

IUPAC Name:

2,4-diisocyanato-1-methylbenzene

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Toluene diisocyanate (TDI)
- Molecular formula: C9H6N2O2
- Molecular weight: 174.1584 g/mol
- Substance type: Organic
- Physical state: liquid
-Smiles: Cc1ccc(cc1N=C=O)N=C=O
- InChI: 1S/C9H6N2O2/c1-7-2-3-8(10-5-12)4-9(7)11-6-13/h2-4H,1H3

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Inc. (Scottdale. Pa.) Or Camm Breeding Laboratories, Inc. (Wayne, N.J.).
- Age at study initiation: young guinea pigs
- Weight at study initiation: no data
- Housing: housed individually in stainless-steel cages with wire-mesh bottoms
- Diet (e.g. ad libitum): Certified Guinea Pig Chow 5026 (Ralston Purina Co. ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): (21 ± 2°C)
- Humidity (%): 40-60%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): Twelve hours of continuous fluorescent lighting was provided daily.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, open

Vehicle:

other: n-Butyl ether was the solvent because of its versatility in preparation of liquid or solid diisocyanates.

Induction 2

Concentration / amount:

Induction concentration:0, 8, 20, or 40%
Challenge concentration: 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: n-Butyl ether was the solvent because of its versatility in preparation of liquid or solid diisocyanates.

Challenge 2

Concentration / amount:

Induction concentration:0, 8, 20, or 40%
Challenge concentration: 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%

No. of animals per dose:

5 guinea pigs/ group

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: 24 hours
- Test groups: 5 guinea pigs
- Control group: 5 guinea pigs
- Site: The animals in each induction group received a total application of 50.0 µl of solution with each animal receiving two 25 µl amounts on separate sites.
- Frequency of applications: no data
- Duration:5 days
- Concentrations: 0, 8, 20, or 40%

B. CHALLENGE EXPOSURE
- No. of exposures: each guinea pig received six challenge applications of TDI in 25 µl aliquots.
- Day(s) of challenge: Five days later induction
- Exposure period: 24 hours
- Test groups: 5 guinea pigs
- Control group: 5 guinea pigs
- Site: The challenge applications were on virgin sites and consisted of one n-butyl ether application and five TDI concentrations
- Concentrations: 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%
- Evaluation (hr after challenge): 24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures: each guinea pig received six challenge applications of TDI in 25 µl aliquots.
- Day(s) of challenge: 14 days after induction
- Exposure period: 24 hours
- Test groups: 5 guinea pigs
- Control group: 5 guinea pigs
- Site: The challenge applications were on virgin sites and consisted of one n-butyl ether application and five TDI concentrations
- Concentrations: 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%
- Evaluation (hr after challenge): 24 hours

OTHER: The hair on the dorsum was clipped 24 hr before the induction concentration was applied.

Challenge controls:

Yes concurrent vehicle

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%

No. with + reactions:

5

Total no. in group:

5

Clinical observations:

100% of the animals had dermal reactions when challenged with 0.1 to 0.4% TDI.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4%. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: 100% of the animals had dermal reactions when challenged with 0.1 to 0.4% TDI. .

Any other information on results incl. tables

All challenge applications except the 0.0% solution elicited a positive response in 75 to 100% of the animals, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material 2, 4-Toluene diisocyanate (CAS No: -584-84-9) was considered to be sensitizing on guinea pigs by open epicutaneous test

Executive summary:

Skin sanitization study was conducted on guinea pigs via open epicutaneous test for test chemical2, 4-Toluene diisocyanate(CAS No: -584-84-9) for exposure period of 24 hours and skin reactions were scored.

 

This study was designed to determine the concentration-dependent elicitation of dermal sensitization in guinea pigs treated with TDI. In this study, young adult guinea pigs received two open, epicutaneous induction applications (25 µL) of 8, 20, or 40% TDI in n-butyl ether on two separate areas.During induction at 20 and 40%concentrations, both the 24- and 48-hr readings (2.0) were much greater than those for the solvent group.

 

 Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4% TDI (25 µL per concentration site). The vehicle application did not produce any significant reactions at challenge. On the other hand, 0.025 to 0.4% TDI produced mean scores of 2.0 to 4.2 in all three TDI groups.All challenge applications except the 0.0% solution elicited a positive response in 75 to 100% of the animals.

 

Fourteen days after induction, the 8, 20, and 40% groups were rechallenged and the 0% group was challenged. Control animals did not respond with dermal hypersensitivity reactions when challenged with applications of n-butyl ether or TDI. For the TDI-induction groups, 100% of the animals had dermal reactions when challenged with 0.1 to 0.4% TDI, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application.

 

Based upon the observations the test material2, 4-Toluene diisocyanate(CAS No: -584-84-9)was considered to be sensitizing on guinea pigs.