Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation: For MDI MT a transient slightly irritating effects was observed in rabbits in a reliable guideline study. Animals were treaded under semiocclusive dressings for 4 hours according to OECD guideline 404 (Gmelin, 2007a). Very slight erythema were seen 1h to 48 hours after the exposure  period. No oedema were indicated at any  time point evaluated. All signs of irritation were fully  reversible within three days. No relevant systemic intolerance reactions were observed. In addition, a test using artificial 3D-Skin model (OECD 431) revealed no corrosive properties of MDI MT (Vohr, 2006). Based on the available study data Desmodur MT is not an irritant to the skin in accordance to CLP classification criteria. 


Eye irritation: In a reliable guideline study (OECD 405) done with rabbits MDI MT was slightly irritating to the eyes of the animals (Gmelin 2007b). No  effects on  cornea nor  iris was seen at any time point evaluated. Moderate to slight redness and chemosis of the  conjunctivae were noted  one to 48 hours after end of exposure. In all animals redness and chemosis of conjunctivae were fully reversible within three days. No systemic intolerance reactions were observed. According to CLP classification criteria Desmodur MT is not an eye irritant.


 


Respiratory tract irritation: There are no acute or repeated inhalation toxicity studies available for MDI MT. A read across with data from the source substances 4,4’-MDI and pMDI was performed with reliable sub-lethal acute and subacute inhalation toxicity studies. Although not all studies were performed according to identical study designs, they all provide sufficient information to conclude that the source  substances 4,4’-MDI and pMDI are respiratory irritants operating via the same MoA.


In an acute inhalation study with mice, pulmonary irritation of 4,4`-MDI was assessed by recording respiratory patterns and frequency (Weyel and Schaffer, 1985). MDI acted primarily as a pulmonary irritant and with a concentration of 32 mg/m³ the respiratory rate was decreased  by 50 %. The magnitude of effect was dependent on the duration of exposure and the exposure concentration. Increases in lung weight were observed in all tested MDI concentrations (lowest tested concentration 6.7 mg/m³). The pulmonary irritation properties of MDI were confirmed by exposing mice via tracheal cannula to 23.6 mg/m³ MDI.


In a dose-range finding study Hotchkiss (2017) noted effects of respiratory tract irritation after single , acute 6 hours inhalation exposure to 4,4’-MDI. This study was designed to provide data on concentration – and time-dependent effects  for bronchoalveolar lavage (BAL) cells in the lung of Wistar rats. Groups of 12 male Wistar rats were exposed for six hours using a nose-only inhalation exposure system to time-weighted average concentrations of 0, 4, 12, and 27 mg 4,4'-MDI/m3. All animals survived the six-hour exposure to the test material. Endpoints indicative of inflammation, macrophage activation, apoptosis/necrosis, and oxidative stress were evaluated immediately following exposure or approximately 18 hours post-exposure (overnight). The single 6 hours exposure to respirable 4,4’-MDI to 4, 12 and 27 mg/m3 resulted in concentration- and time dependent increase in oxidative stress, inflammation, and markers of apoptosis. There was some evidence of inflammation, oxidative stress, and/or apoptosis at every dose, although the clearest effects were observed in the 12 and 27 mg/m3 exposures and especially by 18 hours post exposure. Randazzo (2017) performed a dose-range finding study  with 4,4’-MDI to  establish a maximum tolerated concentration for an in  vivo Comet assay. Male Wistar rats were exposed  once for 6 hours nose-only to  0, 3.2, 7.7, and 11.9 mg/m3. A bronchoalveolar lavage (BAL) was performed from all animals at the scheduled necropsies, and in the BAL fluid (BALF) marker for clinical chemistry, apoptosis and macrophage activation were evaluated and cytology was performed. All animals survived to the scheduled necropsies and no test substance related clinical observations or body weight effects were observed. Compared to control rats, dose dependent increases associated with macrophage activation (β- glucuronidase activity), inflammation (neutrophil infiltration and total protein)) at ≥3.2 mg MDI/m3, apoptosis (Annexin V activity; ≥ 7.7 mg MDI/m3), and necrosis (LDH; ≥ 11.9 mg MDI/m3) were noted in treated groups. From this range-finding study, inhalation exposure to MDI results in marked local acute toxicity at ≥10-12 mg/m3 for a 6 h exposure as identified by inflammation, apoptosis/necrosis and cytotoxicity supporting results from previous studies. The maximum tolerated concentration (MTC) was identified as 11.9 mg/ m3.


In a short-term inhalation toxicity study of polymeric MDI in rats acute irritation was correlated to the alteration of surfactant activity (Pauluhn et al., 1999). When single exposures of various concentrations were applied for 150 min, stimulation of pulmonary irritant receptors was assumed to occur at exposure levels in the range of 2.4 mg/m³. In the second part of the study, rats exposed to 3.3 and 13.7 mg/m³ for 14 days, experienced mild signs of respiratory tract irritation. Light and transmission electron microscopy suggested that this irritation was accompanied by an accumulation of refractile, yellowish-brownish material in alveolar macrophages with concomitant activation of type II pneumocytes. Additionally increased levels of intracellular phospholipids and an increase of bromodeoxyuridine-labelled epithelial cells were detected. The authors suggested that polymeric MDI appears to interact directly with pulmonary surfactant lining fluids.


 


Pauluhn (2000) examined the time course of the relationship between acute pulmonary irritation and acute pulmonary response of Wistar rats exposed to respirable polymeric MDI (pMDI) aerosol of 0, 0.7, 2.4, 8, or 20 mg pMDI/m³ for 6 hours. The time-response relationship of MDI-induced acute lung injury was examined at 0 hours (directly after cessation of exposure), 3 hours, 1 day, 3 days, and 7 days after exposure. Bronchoalveolar lavage (BAL) fluid was analysed for markers indicative of injury of the bronchoalveolar region. Results suggested that respirable pMDI aerosol interacts directly with the air/blood barrier causing increased extravasation of plasma constituents because of increased permeability of capillary endothelial cells. A transient dysfunction of the pulmonary epithelial barrier occurred at a level as low as 0.7 mg/m³ and was interpreted as a dysfunction of pulmonary surfactant. Such dysfunction is thought to correspond to a physiological response. These results show that single or repeat (sub-acute) exposure to highly respirable pMDI aerosols at high concentrations results in lung effects consistent with exposure to an irritant particulate but that recovery occurs upon cessation of exposure. As such, following a six-hours exposure to pMDI aerosol, the NOAEC is 0.7 mg/m³ air whereas the 2.4 mg/m³ air, caused borderline biochemical effects (= LOAEC).


 


In a further study with a similar study design, acute exposures to all tested pMDI-atmospheres (10, 30, or 100 mg/m³) resulted in signs of respiratory tract irritation (abnormal respiratory noise, breathing rate reduced and depth increased, mucous secretions from the nose) and a pattern of lung responses that is consistent with exposure to irritant aerosols (Kilgour et al., 2002). An exposure concentration related body weight loss and increase in lung weight were seen post-exposure, with complete recovery by day 10. Analysis of lung lavage fluid revealed irritation related changes in the lung over the initial days following exposure. These consisted of a pattern of initial toxicity, rapid and heavy influx of inflammatory cells (alveolar macrophages) and soluble markers of inflammation and cell damage, increased lung surfactant, a subsequent recovery and epithelial proliferative phase (e.g. bronchiolar and type II cell hyperplasia). Finally, a return to the normal status quo of the lung (by day 30 post exposure) was observed. In the same report repeated exposure over 28 days (1, 4, or 10 mg/m³) produced an increase in lung weight in the high dose group which resolved following the 30-day recovery period. Other effects seen were again consistent with exposure to irritant aerosols, but were less severe than those seen in the acute study. 1 mg/m³ was derived as the LOAEL for effects on surfactant homeostasis (NOAEL 1 mg/m³) and (reversible) bronchiolitis, whereas the NOAEL for pneumonitis is less than 10 mg/m³.


 


Based on the structure similarities of source and target substance and the hypothesized MoA, MDI MT should be classified as respiratory tract irritant STOTsingleCat3 (H335) EU GHS 1272/2008 CLP.


The source substances 4,4’-MDI is officially classified with STOTsingleCat3 (H335) EU GHS 1272/2008 CLP.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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: 2.3-3.0 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
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: the surrounding untreated skin area of test animals served as control
Amount / concentration applied:
Amount: 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours as well as 7 and 14 days after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin area carefully washed with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to DRAIZE
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: fully reversible within 1 day in respect of the result 1 h post application
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: fully reversible within 1 day in respect of the result 1 h post application
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 72 h
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: no oedema observed during the study
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: fully reversible within 1 day in respect of the result 1 h post application
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: fully reversible within 1 day in respect of the result 1 h post application
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: fully reversible within 1 day in respect of the result 1 h post application
Remarks on result:
other: test compound could not be removed completely from skin, 24 h- 72- h and 14 d desquamation after patch removal
Irritant / corrosive response data:
In conjugation with the chemical properties and the fact that the test compound could not be removed completely from the skin, the most plausible explanation for the desquamation is residue of test compound adhered to the treated skin area. This was not regarded as irritation to the skin.
Other effects:
No systemic intolerance reactions were observed.

Table 1: Summary of irritant effects on the skin (Exposure: 4 hours)


Observation time               1h 24h 48h 72h day7 day14

(after patch removal)
Animal 1
Erythema (redness)
and eschar formation            1   0   0   0    0    0
Oedema formation                0   0   0   0    0    0

Animal 2
Erythema (redness)
and eschar formation            1   1   1   0    0    0
Oedema formation                0   0   0   0    0    0

Animal 3
Erythema (redness)
and eschar formation            1   1   1   0    0    0
Oedema formation                0   0   0   0    0    0



- = no further examination

Interpretation of results:
GHS criteria not met
Remarks:
slightly irritating
Conclusions:




Classification: not irritating
Executive summary:

In a dermal irritation/corrosion study according to OECD TG 404 Desmodur MT was applied under semiocclusive dressings for 4 hours to the shaved skin of 3 female rabbits. Skin irritation was assessed after 1, 24, 48, 72 hours as well as 7 and 14 days using the Draize scale. The mean irritation index for erythema was 0.5 of max. 4 (0.0 - 0.7), the mean irritation index for edema was 0.0 of max. 4. Signs were fully reversible in all animals within three days. The weight of these evidences indicates that the test substance may be considered as "slightly irritating to the skin". No relevant systemic intolerance reactions were observed.

According to classification criteria Desmodur MT is not an irritant to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
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: 2.4-2.7 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
Vehicle:
unchanged (no vehicle)
Controls:
other: one untreated eye of test animals served as control
Amount / concentration applied:
Amount: 0.1 ml

Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48, 72 hours post application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye was not rinsed for at least 24 hours following instillation.

SCORING SYSTEM: according to DRAIZE
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

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        2    2    1   0    -     -     -     
Chemosis conjunctivae       1    1    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        3    2    1   0    -     -     -     
Chemosis conjunctivae       1    1    1   0    -     -     -     
Animal 3
Degree of cornea opacity    0    0    0   0    -     -     -     
Area of cornea opacity      0    0    0   0    -     -     -     
Iris                        1    0    0   0    -     -     -     
Redness conjunctivae        3    3    2   0    -     -     -     
Chemosis conjunctivae       1    1    0   0    -     -     -    

- = no further examination 

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

               

Interpretation of results:
GHS criteria not met
Remarks:
slightly irritating
Conclusions:



Classification: not irritating
Executive summary:

In an eye irritation study according to OECD TG 405 Desmodur MT was instilled into the conjunctival sac of one eye of 3 female rabbits. Eye irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. The mean irritation index for redness of conjunctivae was 1.2 of max. 3 (1.0 - 1.7), the mean irritation index for chemosis of conjunctivae was 0.4 of max. 4 (0.3 - 0.7). Signs were fully reversible in all animals within three 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.

 

According to classification criteria Desmodur MT is not an irritant to the eyes.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies with Desmodur MT (MDI MT), classification for skin and eye irritation is not warranted according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.


 With regard to respiratory irritation the classification of 4,4'-MDI (CAS No.101-68-8) was considered for the classification of MDI MT (CAS No.147993-65-5) according to CLP Regulation (EC) No.1272/2008:


 GHS: STOT Single Exp.3 (H335: may cause respiratory irritation).