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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
See the full article in the attachement.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Mouse Ear Swelling Test:
Dose dependent contact hypersensitivity responses to both DCC and DIC were demonstrated by the MEST. Sensitizing concentrations as low as 0.006% DCC produced significant ear swelling 24 and 48 hr after application compared to the background control group (Fig 4). Similarly, sensitization with concentrations as low as 0.3% DIC produced a significant increase in percent ear swelling 24 hrs post challenge. By 48 hrs post challenge, 1.5% DIC was the lowest concentration producing a statistically significant response (Fig 5). No significant differences were seen in body weight changes between animals dosed with vehicle or test article in any of the MEST studies. The positive control groups experienced a significant increase in percent ear swelling as compared to the background positive at both the 24 and 48 hr time points (representative studies are shown in Figs 4 and 5).
GLP compliance:
not specified
Type of study:
mouse ear swelling test
Justification for non-LLNA method:
Furthermore, the MEST was a more effective indicator of sensitization potential than the LLNA in these studies. In conducting this battery of assays for numerous years, no pattern has occurred with regards to the sensitivity of LLNA vs. the MEST. There has been a positive correlation between these assays at highly sensitizing concentrations, but at lower concentrations the sensitivity of these assays varies,between chemicals. For these carbodiimides, the murine models of irritation and hypersensitivity used in this study correlate well with reported human case studies.

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N'-methanetetraylbis(1-methylethylamine)
EC Number:
211-743-7
EC Name:
N,N'-methanetetraylbis(1-methylethylamine)
Cas Number:
693-13-0
Molecular formula:
C7H14N2
IUPAC Name:
(propan-2-yl)({[(propan-2-yl)imino]methylidene})amine
Test material form:
liquid

In vivo test system

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female
Details on test animals and environmental conditions:
no data

Study design: in vivo (non-LLNA)

Details on study design:
The Mouse Ear Swelling Test (MEST) followed the original procedure described by Gad et all0 with only minor modifications. Prior to dosing, mice were weighed, tattooed, and anesthetized so the dorsal lumbar area of each mouse could be shaved. Initial concentrations of DCC and DIC evaluated were the O.lMNC, OSMNC, and MNC. Lower concentrations were tested when necessary to elicit a no-effect level (Table I). Beginning on day I, 50 p1 of test article or vehicle was applied to the shaved site of each animal. The same procedures were repeated for two more days and then the mice were left untreated for four days (days 4-7). On day 8, right ear thickness of each mouse was measured in duplicate and averaged prior to challenge. After measurement, mice were challenged with 12.5 pl of vehicle or test article (MIC concentration) on the dorsal and ventral surfaces of the right ear pinna. The right ear then was measured in duplicate 24 and 48 hours (i2 hr) after challenge and averaged. The percent ear swelling was calculated for each time point as described for the imtancy assay. Mean percent ear swelling for each dose group was compared to the mean percent ear swelling for the background control (BC, sensitization with acetone and challenge with MIC) for significance and dose response. The BC group was used as the control to account for swelling caused by irritation.
Challenge controls:
After measurement, mice were challenged with 12.5 pl of vehicle or test article (MIC concentration) on the dorsal and ventral surfaces of the right ear pinna.
Positive control substance(s):
yes
Remarks:
1-fluoro-2,4 dinitrobenzene

Results and discussion

In vivo (non-LLNA)

Results
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.03%, 0.15%, 0.3%, 1.5%, 3%
Clinical observations:
Sensitization with concentrations as low as 0.3% DIC produced a significant increase in percent ear swelling 24 hrs post challenge
Remarks on result:
positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Skin Sens 1 H317
Dose dependent contact hypersensitivity responses to DIC were demonstrated by the Mouse Ear Swelling Test (MEST).
Executive summary:

Skin Sens 1 H317

Sensitizing concentrations as low as 0.006% DCC produced significant ear swelling 24 and 48 hr after application compared to the background control group (Fig 4). Similarly, sensitization with concentrations as low as 0.3% DIC produced a significant increase in percent ear swelling 24 hrs post challenge. By 48 hrs post challenge, 1.5% DIC was the lowest concentration producing a statistically significant response (Fig 5). No significant differences were seen in body weight changes between animals dosed with vehicle or test article in any of the MEST studies. The positive control groups experienced a significant increase in percent ear swelling as compared to the background positive at both the 24 and 48 hr time points (representative studies are shown in Figs 4 and 5).