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Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Referenceopen allclose all

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1'-Methylenebis(4-isocyanatobenzene) and 1,1'-methylenebis(4-isocyanatobenzene) homopolymer and their reaction products with [(methylethylene)bis(oxy)]dipropanol and butane-1,3-diol and propane-1,2-diol
EC Number:
701-393-8
Molecular formula:
NCO.(C29H20N4O2)x.C13H10.[(C24H30N2O6).(C29H20N4O2)y]n.NCO and NCO.(C29H20N4O2)x.C13H10.[(C19H20N2O4).(C29H20N4O2)y]n.NCO and NCO.(C29H20N4O2)x.C13H10.[(C18H18N2O4).(C29H20N4O2)y]n.NCO n = 0-2, x = y = 0-1
IUPAC Name:
1,1'-Methylenebis(4-isocyanatobenzene) and 1,1'-methylenebis(4-isocyanatobenzene) homopolymer and their reaction products with [(methylethylene)bis(oxy)]dipropanol and butane-1,3-diol and propane-1,2-diol
Details on test material:
Identification: Suprasec 2029
Lot/Batch No.: RZW91
Cas no.: No CAS number is allocated to this substance
Expiration Date: 16 Sep 2009
Physical Description: Clear colorless liquid/clear colorless viscous liquid
Composition/Purity: 4,4'-METHYLENEDIPHENYL DIISOCYANATE, OLIGOMERIC REACTION PRODUCTS WITH BUTANE-1,3-DIOL, 2,4'-DIISOCYANATODIPHENYLMETHANE, [(METHYLETHYLENE)BIS(OXY)]DIPROPANOL AND PROPANE-1,2-DIOL
Stability The test article was expected to be stable under standard laboratory conditions, under nitrogen blanket and protected from moisture, for the duration of testing.
Storage Conditions: Room temperature (10-30ºC), under nitrogen and protected from moisture
NCO value: 24.3 %,
viscosity @ 25°C: 489 mPas
Specific details on test material used for the study:
originally wrongly identified as MDI Mixed Isomers/1,3-BD/TPG/PG, but subsequent corrected to 4,4’-MDI/4,4’-MDI homopolymer/1,3-BD/TPG/PG

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Total Number: Three
Gender: Male
Age Range: 18 weeks at start of dosing; records of dates of birth for animals used in this study are retained in the Calvert archives.
Body Weight Range: 2.9 to 3.3 kilograms at the outset (Day 1) of the study.
Animal Source: Harlan, Oxford, MI
Experimental History: Purpose-bred and experimentally naïve at the outset of the study.
Identification: Ear tag and cage card

ENVIRONMENTAL CONDITIONS
Housing: Animals were individually housed in compliance with USDA Guidelines. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
Lighting: 12 hours light/12 hours dark
Room Temperature: 18 to 24°C
Relative Humidity: 42 to 76%
Food: All animals had access to PMI Certified Hi-Fiber Rabbit Diet #5325 as per Calvert SOP. The lot number(s) and specifications of each lot used are archived at Calvert. No contaminants were known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which are maintained in the Calvert archives.
Water: Tap water was available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP’s. No contaminants were known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis are maintained in the Calvert archives.
Acclimation: Study animals were acclimated to their housing for a minimum of 5 days prior to dosing.

IN-LIFE DATES (original): From: 27 Jul 2009 To: 11 Aug 2009
IN-LIFE DATES (repeated): From: 27 Jan 2010 To: 10 Feb 2010

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
A dose of 0.5 ml of the liquid test article was applied to each of the test sites. The test article was applied directly on the intact skin sites.
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
The pH of the article was determined by the testing facility prior to experimental start (pH meter) and after in-life termination (litmus paper). The methods of pH determinations were pH Testr 3+ Oakion and pH (litmus) paper.

-pH meter----------pH (litmus) paper

-5.55--------------5


Within 24 hours before initiation of the test, fur was removed from the dorsal trunk of each animal by clipping. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used.

Each test article was applied to an area (~5cm x 5cm) on the dorsal trunk of each animal and covered with a gauze patch. In the case of liquids or some pastes, it may be necessary to apply the test article to the gauze patch and then apply that to the skin. Each patch was loosely held in contact with the skin with a sheet of rubber dam. The trunk of the animal was wrapped with an elastic bandage dressing, which was held in place with non-irritating tape for a four-hour exposure period. At the end of the exposure period, residual test article was removed using corn oil, without altering the existing response or the integrity of the epidermis. The corn oil was placed on the gauze, saturated and allowed to soak into the skin for ~15 minutes or until the gauze could easily be removed before being wiped with gauze. The degree of erythema and edema was evaluated at each site according to the Draize. Photographs were taken of the sites at every observation period for each animal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal #3
Time point:
14 d
Score:
>= 1 - <= 3
Max. score:
3
Irritation parameter:
edema score
Basis:
animal #2
Time point:
14 d
Score:
>= 1 - <= 2
Max. score:
3
Irritation parameter:
edema score
Basis:
animal #1
Time point:
14 d
Score:
>= 1 - <= 2
Max. score:
2
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
14 d
Score:
>= 1 - <= 3
Max. score:
3
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
14 d
Score:
>= 1 - <= 3
Max. score:
3
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
14 d
Score:
>= 1 - <= 3
Max. score:
3
Irritant / corrosive response data:
Dermal Irritation and Corrosivity:

The following is a summary of the most severe dermal responses observed:

-Dermal Responses----------------------------------Comments
Moderate to severe erythema and moderate edema----Sloughing and flaking of the skin observed
Other effects:
No mortality was observed during the study. No clinical signs were recorded during the course of the study.

Body weight data are presented in the table below:

Body Weights (kg)
Animal No.----------Sex---------Initial-------Final
2707---------------M-----------2.5---------2.7
2708---------------M-----------2.5---------2.9
2709---------------F------------2.3--------2.5

Any other information on results incl. tables


Table 4: Dermal Observations/Post Treatment (Site 4 - Test Material 4)


 






































































































































































































































































































































              30-60 minutes post-dose             24 hours (Day 2)
 Rabbit No Erythema Edema Necrosis Fissuring Sloughing Erythema Edema Necrosis Fissuring Sloughing
 2707M 1222
 2708M 12- - 1 1 - - -
 2709F 1 2 - - - 11 - - -
              48 hours (Day 3)             72 hours (Day 4)
 2707M 1 2 - - - 1 2 - - -
 2708M 1 1 - - - 1 1 - - -
 2709F 2 2 - - - 2 2 - - -
              Day 5             Day 6
 2707M 1 2 - - - 1 2 - - -
 2708M 1 1 - - - 1 1 - - -
 2709F 2 2 - - - 2FL 2 - - -
              Day 7             Day 8
 2707M 2FL 2 - - - 2FL 2 - - -
 2708M 2FL 2 - - - 3FL 2 - - -
 2709F 2FL 2 - - - 3FL 2 - -
              Day 9             Day 10
 2707M 3FL 2 - - - 3FL 2 - - -
 2708M 3FL 3 - - - 3FL 3 - - -
 2709F 3FL 3 - - - 3FL 3 - - -
              Day 11             Day 12
 2707M 3FL 2 - - - 3FL 2 - - -
 2708M 3FL 2 - - - 3FL 2 - - -
 2709F 3FL 3 - - - 3FL 3 - - -
              Day 13             Day 14
 2707M 3FL 2 - - + 3FL 2 - - -
 2708M 3FL 2 - - - 3FL 2 - - -
 2709F 2FL 2 - - - 2FL 2 - - -

- = Not observed


+ = Observed


FL = Flaking


 


 


Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the results of this Comparative Primary Dermal Irritation Study in Rabbits, the following is the classification of the test article when applied for four hours to the skin of rabbits and removed according to the methodology utilized in this assay ;

--EEC Irritation Rating------GHS Classification-------Corrosivity

---Irritant -------------------Irritant – Category 2-----Non – Corrosive

Executive summary:

Results from earlier studies showed that the test material cured with moisture in the skin and adheard to the application site.  Removal of the cured test material at the end of the treatment period compromised the integritiy of the skin leading to significant erythema and edema.  


The purpose of this current study was to determine and compare the potential irritant and/or corrosive effects of five test articles on the skin of rabbits when the materials were removed in a prescribed method (soaking in corn oil prior to removal) to insure that removal had no effect on the integrity of the skin sites.


The test material was initially applied to five sites on the clipped dorsal trunk of three New Zealand White rabbit for a four-hour exposure period at 0.5 mL per site. As per design of this comparative assay, the patches were saturated with corn oil for a minimum of 15 minutes prior to removal in order to reduce / eliminate the possibility of mechanical damage to the skin. Observations for dermal irritation were recorded for the rabbits 30-60 minutes after patch removal, and then 24, 48 and 72 hours (±1 hour) and daily through Day 14. Grading of irritation was according to the method of Draize. Photographs were taken of the sites at every observation period for each animal.


 


The following is a summary of the most severe dermal responses observed:


 















Test ArticleDermal ResponsesComments
Test material 4 Moderate to severe erythema and moderate edema Sloughing and flaking of the skin observed

 


Based on the results of this Comparative Primary Dermal Irritation Study in Rabbits, the following is the classification of the test article when applied for four hours to the skin of rabbits and removed according to the methodology utilized in this assay:


 


 























Test ArticleEEC Irritation RatingGHS Classification Corrosivivity
 Test material 4 Irritant Irritant – Category 2 Non – Corrosive