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EC number: 237-198-5 | CAS number: 13684-56-5
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1987-07-27 to 1988-10-11
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- Magnusson and Kligman test (1970)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- Magnusson and Kligman test (1970)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Some exceptions. During the acclimation period emaciation was observed in four female guinea pigs, but these females remained in the main study. The test of the positive control group treated with DNCB was not run under GLP-conditions in 1987.
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The study was performed prior to adoption of the OECD test guideline for the LLNA (OECD 429, 2010).
Test material
- Reference substance name:
- Desmedipham
- EC Number:
- 237-198-5
- EC Name:
- Desmedipham
- Cas Number:
- 13684-56-5
- Molecular formula:
- C16 H16 N2 O4
- IUPAC Name:
- ethyl 3´-phenylcarbamoyloxycarbanilate
- Test material form:
- solid: particulate/powder
- Details on test material:
- The test material is Desmedipham.
Constituent 1
- Specific details on test material used for the study:
- The test material is in a white powder form.
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- Test system: Dunkin-Hartley albino guinea pigs
Rationale: Recognised by the international guidelines as the recommended test system
Total number of animals: 15 males animals 15 females
Age at Pretest: 7 - 8 weeks
Body weight at pre-test: Males: 406 - 412 g Females: 391 - 479 g
Identification: By unique cage number and corresponding ear tags.
Randomization: Randomly selected at time of delivery.
Acclimation: One week under test conditions after veterinary examination.
A control group is tested twice a year as a sensitivity check of the guinea pig strain. The most recent test was run during July 1987.
Standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour and hourly monitored environment with temperature 22 + -3 degrees centigrade, relative humidity 40-70%, 12 hours artificial fluorescent light/12 hours dark, music/light period.
Accommodation
Individually in Makrolon type-3 cages with standard softwood bedding.
Diet
Pelleted standard Kliba 342, Batch 37/87 guinea pig breeding/ maintenance diet ad libitum.
Water
Community tap mater from Itingen, ad libitum. Results of analysis for contaminants are included in this report.
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal
- Vehicle:
- other: Mixture of polyethyleneglycol (PEG 400) and physiological saline (7:3)
- Concentration / amount:
- 0.5%
- Day(s)/duration:
- Single intradermal injection
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Mixture of polyethyleneglycol (PEG 400) and physiological saline (7:3)
- Concentration / amount:
- 25%
- Day(s)/duration:
- Single topical induction
- Adequacy of induction:
- other: No signs of irritation
Challengeopen allclose all
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Concentration / amount:
- 25%
- Day(s)/duration:
- Single topical exposure
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Mixture of polyethyleneglycol (PEG 400) and physiological saline (7:3)
- Concentration / amount:
- 25%
- Day(s)/duration:
- Single topical application
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 5 males, 5 females for the vehicle control group and 10 males, 10 females for the test article group.
- Details on study design:
- Preliminary study
Desmedipham caused slight erythema (grade 1) and slight edema (grade 1) at all tested concentrations (0.5, 1, 3, and 5%) administered by intradermal injection. After the epicutaneous application no skin reactions were observed on the shaved flanks of four guinea pigs at the tested concentrations of 3, 5, 10, 25% desmedipham in the vehicle. Desmedipham was diluted in polyethylene glycol (PEG 400) and physiological saline (7:3). The concentrations of the test article selected were 0.5% for intradermal injections and 25% for topical applications in the main study.
Main study
The skin sensitisation potential of technical desmedipham was assessed in 20 (10 males/10 females) Dunkin Hartley albino guinea pigs, weighing from 391 to 492 g. Additionally 10 animals (5 males/5 females) were used as a vehicle control group. The mixture of polyethyleneglycol (PEG 400) and physiological saline (7:3) was used as a dosing vehicle. DNCB (2,4-dinitro-1-clorobenzene) was used as a positive control article.
During the induction, three double intradermal injections of 0.1 ml volume were administered in the shoulder region of the test animals. The intradermal injections were a) Freund’s complete adjuvant plus the vehicle in the ratio 50:50, b) 0.5% solution of desmedipham in the vehicle, c) 0.5% desmedipham emulsified in 50:50 mixture of Freund’s complete adjuvant and the vehicle. One week later, the same area was dermally treated with desmedipham 25% in the vehicle and covered with occlusive dressings for 48 hours. The control animals were treated as above with the omission of the test article.
The challenge phase was conducted 2 weeks later. Topical applications were made with a) a 25% concentration of desmedipham in the vehicle placed on the left flank and b) with the vehicle alone placed on the right flank. The occlusive dressings were removed approximately 24 hours later. The control animals were treated in the same way as above. The second challenge was performed two weeks later using a similar method to the first challenge with the exception that the solutions (25% desmedipham, vehicle) were applied to the opposite flank. The control animals were treated with vehicle alone. The challenge site was evaluated immediately and then 24 and 48 hours after removal the patch. The Exact Fisher test for comparison of the basic probability was used in the statistical analysis. - Positive control substance(s):
- yes
- Remarks:
- DNCB (2,4-dinitro-1-clorobenzene) was used as a positive control. The positive control test with DNCB was conducted in July 1987, when 100% of the test group animals (15) reacted positively.
Results and discussion
- Positive control results:
- DNCB (2,4-dinitro-1-clorobenzene) was used as a positive control. The positive control test with DNCB was conducted in July 1987, when 100% of the test group animals (15) reacted positively.
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- negative control
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: Overall results (24 +48 hours)
- Group:
- positive control
- No. with + reactions:
- 15
- Total no. in group:
- 15
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- DNCB (2,4-dinitro-1-clorobenzene) was used as a positive control. The positive control test with DNCB was conducted in July 1987, when 100% of the test group animals (15) reacted positively
Any other information on results incl. tables
No deaths occured during the test. During acclimation, emaciation was observed in 3/5 control female guinea pigs and 1/10 test female guinea pigs. With the exception of these females, the body weight gain of all other animals was not affected during the test procedure. Erythema, edema, necroses and exfoliation around the injection sites were noted in the control and test animals during the induction phase. After the first and second challenge applications, there were no skin responses in the vehicle control and test animals (0/10 and 0/20, respectively). Desmedipham technical was considered to possess no skin sensitizing potential in albino guinea pigs.
Positive erythema reactions after first challenge procedure.
| After 24 h | After 48 h | |||
| positive | negative | positive | negative | |
| Desmedipham technical | 0 | 20 | 0 | 20 |
| % positive reaction. | 0 | - | 0 | - |
| Vehicle control | 0 | 10 | 0 | 10 |
| % positive reaction. | 0 | - | 0 | - |
Positive erythema reactions after second challenge procedure.
| After 24 h | After 48 h | |||
| positive | negative | positive | negative | |
| Desmedipham technical | 0 | 20 | 0 | 20 |
| % positive reaction. | 0 | - | 0 | - |
| Vehicle control | 0 | 10 | 0 | 10 |
| % positive reaction. | 0 | - | 0 | - |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Desmedipham technical (99.2%) was not found to be a dermal sensitizer in the guinea pig maximisation test. In general testing should be performed using healthy animals and in this study emaciation was observed in four females already during acclimation and then during the test period.
- Executive summary:
With the procedures used in this experiment, no differences between the test group and the vehicle-treated controls were evident after the first and second epidermal challenge application of DESMEDIPHAM TECHNICAL.
DESMEDIPHAM TECHNICAL is considered to possess no skin sensitizing (contact allergenic) potential in albino guinea pigs.
No toxic symptoms were evident in the guinea pigs of either the control nor test group.
No death occurred.
The study does not meet the GHS criteria.
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