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Diss Factsheets

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.10.2010-10.11.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Justification for type of information:
Hypothesis: Eye irritation of the category substances is driven by the rapid reaction of NCO group on bioaccessible MDI with extracellular biological nucleophiles such as glutathione and protein, resulting in ocular irritation and an acute inflammatory response. All substances will be classified as Category 2 eye irritants according to the worst case substances (mMDI and pMDI).

Justification: Although eye irritation studies are not available for all substances of the MDI category, on the basis of a general consistency of effects in the data matrix and a common MoA, it can be assumed with high confidence that all MDI substance are eye irritants.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-methylenediphenyl diisocyanate
EC Number:
219-799-4
EC Name:
2,2'-methylenediphenyl diisocyanate
Cas Number:
2536-05-2
Molecular formula:
C15H10N2O2
IUPAC Name:
1,1'-methylenebis(2-isocyanatobenzene)
Details on test material:
- Name of test material (as cited in study report): MDI 22
- Physical state: solid
- Purity: approx. 100 % (as indicated by the sponsor)
- Lot/batch No.: WRS 3792
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Crl:KBL(NZW)BR
- Sex: female
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: adult
- Weight at study initiation: 2.7-3.1 kg
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 25
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: one untreated eye of test animals served as control
Amount / concentration applied:
Amount: 0.1 g

Duration of treatment / exposure:
The treated eye was rinsed approximately 1 hour following instillation.
Observation period (in vivo):
1, 24, 48, 72 hours and 7 days post application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The trated eye was rinsed approximately 1 hour following instillation with 0.9 % saline

SCORING SYSTEM: according to DRAIZE

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 1 day in respect of the result 1 hour post application
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
3
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: mean score after 72 hours: 0.7
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: mean score after 72 hours: 0.0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score after 72 hours: 1.3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 1 day 1 day in respect of the result 1 hour post application
Remarks on result:
other: mean score after 72 hours: 0.0

Any other information on results incl. tables

Table 1: Summary of irritant effects on the eye

 

Observation time           1h  24h  48h  72h  day7 day14 day21
Animal 1
Degree of cornea opacity    0    0    0   0    -     -     -     
Area of cornea opacity      0    0    0   0    -     -     -     
Iris                        0    0    0   0    -     -     -     
Redness conjunctivae        1    0    0   0    -     -     -     
Chemosis conjunctivae       0    0    0   0    -     -     -     
Animal 2
Degree of cornea opacity    0    0    0   0    -     -     -     
Area of cornea opacity      0    0    0   0    -     -     -     
Iris                        0    0    0   0    -     -     -     
Redness conjunctivae        1    1    1   0    -     -     -     
Chemosis conjunctivae       0    0    0   0    -     -     -     
Animal 3
Degree of cornea opacity    0    0    0   0    0     -     -     
Area of cornea opacity      0    0    0   0    0     -     -     
Iris                        0    0    0   0    0     -     -     
Redness conjunctivae        2    2    1   1    0     -     -     
Chemosis conjunctivae       1    0    0   0    0     -     -    

- = no further examination 

Animal 1,2 and 3 (1hour p.a.): test compound adhered to cornea and conjunctiva

               

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:


Based on the test results, GHS criteria for classification are not met
Executive summary:

In an eye irritation study according to OECD TG 405 MDI 22 (2,2'-MDI) was instilled into the conjunctival sac of one eye of 3 female rabbits. Eye irritation was assessed after 1, 24, 48 and 72 hours and 7 days using the Draize scale. In this study MDI 22 shows slight irritant effects (mean irritation index for redness conjunctivae = 0.7 of max. 3) which were fully reversible within 7 days. No irritation effects were seen at cornea or iris 24 hours after instillation. The weight of these evidences indicates that the test substance may be considered as "slightly irritating to the eyes". No systemic intolerance reactions were observed.


Based on the test results, GHS criteria for classification are not met. However, 2,2’-MDI is harmonized classified in the European Union with H319 CLP Annex VI Regulation (EC) No 1272/2008 (CLP regulation).