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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
Study period:
April - May 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
e.g. readings were performed 24 and 48 h after start of challenge application, no data on test substance purity, no information on stability testing in the vehicle used

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
e.g. readings were performed 24 and 48 hours after start of challenge application (no 48 and 72-hour value)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test performed prior to LLNA guideline.

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-methylenedicyclohexyl diisocyanate
EC Number:
225-863-2
EC Name:
4,4'-methylenedicyclohexyl diisocyanate
Cas Number:
5124-30-1
Molecular formula:
C15H22N2O2
IUPAC Name:
1,1'-methylenebis(4-isocyanatocyclohexane)
Details on test material:
- Purity: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Strain: Pirbright, Hoe: DHPK (SPF - LAC.) /Boe.
- Sex: no data
- Source: Lippische Versuchstierzucht, Extertal, Germany
- Age at study initiation: no data
- Weight at study initiation (mean): 280 g
- Housing: in groups of 2 per cage, Makrolon type III-cages (14 cm x 25 cm x 42 cm)
- Diet and Water: ad libitum
- Acclimation period: approx. 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 45-55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
paraffin oil
Concentration / amount:
10 % / 0.05 mL
Day(s)/duration:
Day 0
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % / 0.5 mL
Day(s)/duration:
Day 7 / exposure 48 h
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
100 % / 0.5 mL
Day(s)/duration:
after 3 weeks / exposure 24 h
No. of animals per dose:
20 test animals / 20 controls
Details on study design:
RANGE FINDING TESTS: For range finding 0.5 mL test substance formulation at 100, 75 , and 50 % (in paraffin oil) was applied once on 2 animals. Primary irritation was not detected in any of the concentrations tested.

MAIN STUDY
Prior to treatment the fur of the shoulder region was shorn (ca. 8 x 5 cm).

A. INDUCTION EXPOSURE
Day 0: Intradermal induction - pairwise injections in the shoulder region of 0.05 mL
1) test substance 10 % in vehicle
2) test substance 10 % in FCA (FCA diluted 1:1 in oleum arachidis)
3) FCA diluted 1:1 in aqua dest.
Control animals received 1) FCA undiluted 2) paraffin oil 10 % in in FCA (FCA diluted 1:1 in oleum arachidis) and 3) paraffin oil undiluted.

Day 7: Topical induction - 0.5 mL undiluted test substance or vehicle were applied on the same sites used for intradermal injection; closed patch treatment for 48 hours

B. CHALLENGE EXPOSURE
3 weeks after dermal induction: challenge - 0.5 mL undiluted test substance is applied on the left flank and 0.5 mL vehicle on the right flank, closed patch treatment for 24 hours, readings after patch removal, i.e. 24 hours after challenge start and at 48 hours after challenge.

Assessment scheme:
0 = no skin reaction   
0.5 = slight, spotted (i.e. irregular) erythema
1 = slight, confluent, or moderately spotted erythema   
2 = moderate erythema    
3 = severe erythema or edema
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
20
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
19
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
20

Any other information on results incl. tables

24 and 48 hours after challenge start animals exhibited slight up to moderate erythema (24 hours after challenge start: 20/20 positive, mean score 1.18; 48 hours after challenge: 19/20 positive, mean score 1.10)

The negative control group that received the vehicle alone for challenge showed no skin reactions.

Applicant's summary and conclusion

Executive summary:

The potential for skin sensitization of 4,4´-Methylenedicyclohexyl diisocyanate was tested in a guinea pig maximization test similar to OECD 406. The test item was administered at a concentration of 10 % intradermally (with FCA, in paraffin oil) and 100 % epidermally (occlusive) to 20 guinea pigs. After challenge at a 100 % concentration slight to merked erythema was observed in 20/20 animals 24 hours after challenge and in 19/20 animals 48 hours after challenge. No skin reactions were observed for control animals. Thus, a sensitising potential of the test substance can be concluded.