1-chloro-2,4-dinitrobenzene

Immunotoxicity

Administrative data

Endpoint:

immunotoxicity: short-term dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: The study is not relevant for safety evaluation of DNCB because it investigates the mechansims of reduced sensitivity after dermal sensitisation

Data source

Reference

Reference Type:

publication

Title:

Local and systemic desensitization induced by repeated epicutaneous hapten application

Author:

Boerrigter, G.H.; Scheper, R.J.

Year:

1987

Bibliographic source:

J. Invest. Dermatology 88:3-7 (1987)

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Guinea pigs were treated repeatedly dermally with DNCB to sensitize and lateron desensitize there immune system

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-2,4-dinitrobenzene

EC Number:

202-551-4

EC Name:

1-chloro-2,4-dinitrobenzene

Cas Number:

97-00-7

Molecular formula:

C6H3ClN2O4

IUPAC Name:

1-chloro-2,4-dinitrobenzene

Details on test material:

no data

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

female

Administration / exposure

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

Sensitisation: 100 µl 1% solution in ethanol, epicutaneous, ear,
Desensitisation: 3 days after sensitisation, 24x / 8 weeks, 50 µl 0.2% in ethanol, right flank or ears,
Challenge: 2 days after final desensitisation treatment, 20 µl 0.3% in ethanol contralateral flank

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Intermittent treatement for ca. 9 weeks

No. of animals per sex per dose:

5

Details on study design:

Animals were sensitised by dermal exposure to 1% DNCB solution (ear) and afterwards desesensitised by repeated treatment with 0.1 % solutions (24 x in 8 weeks). 24 h after each treatment the local (site of application) skin reaction was evaluated and found to drecrease steadily. A further challenge test on the contralateral site was performed at the end of the 8 week period, which showed reduced sensitivity also at distant skin sites.

Examinations

Observations and clinical examinations performed and frequency:

Parameters evaluated: erythema and skin thickness at site of application, reactions on the contralateral skin (systemic sensitisation), formation of anti-dinitrophenyl antibodies in an ELISA, histopathology of treated skin,

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Gross pathological findings:

not examined

Specific immunotoxic examinations

Specific cell-mediated immunity:

effects observed, treatment-related

Any other information on results incl. tables

Animals were sensitised by dermal exposure to 1% DNCB solution (ear) and afterwards desesensitised by repeated treatment with 0.1 % solutions (24 x in 8 weeks, flank). 24 h after each treatment the local (site of application) skin reaction was evaluated and found to drecrese steadily. A further challenge test on the contralateral site was performed at the end of the 8 week period, which showed macroscopically reduced sensitivity also at distant skin sites compared to animals sensitised but not treated repeatedly.

Histopathological examination of the sites of treatement showed an increase of the number of inflammatory cells with increasing number of treatments although the visible reaction decreased.

Desensitisation reveresd when animals were left untreated for 5 weeks and reactions were comparable to those of freshly sensitised animals.

Applicant's summary and conclusion

Conclusions:

The continuous dermal treatment of guinea pigs with DNCB can reduce local as well as systemic responsiveness to the agent. However, as this effect is reversible it has no relevance for the risk assessment of DNCB