Registration Dossier

Administrative data

Description of key information

In a dermal irritation study with DESMODUR BL 3175, conducted according to OECD 404 guideline in compliance with GLP, mean individual scores 
were 2.0/2.0/2.0 for erythema and 0.0/0.0/0.0 for oedema. At the end of the observation period, the scores for erythema at Day were
1.0/1.0/1.0, not completeley reversible.
In an eye irritation study conducted according to OECD 405 guideline in compliance with GLP, mean individual scores were 0.0 for cornea, iris,
conjunctivae and chemosis.
In a sensory irritation study in which the protocol is based on the ASTM method designed E981-84, the exposure technique met the requirements of
the OECD 403 guideline. The RD50 was 1450 mg/m3. No mortality has been observed up to highest dose.
Slight bradypnea has been observed at the highest dose. No body weight and no indications of specific organ changes observed. The pulmonary
function test showed that the preparation in aerosol induced a concentration-dependant decrease in the respiratory rate.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-11-28 to 1989-12-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-conducted guideline study, GLP, no deviations
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult
- Weight at study initiation: animal 1=2.9 kg; animal 2=3.3 kg; animal 3=3.2 kg
- Housing: individually housed in stainless steel cages
- Diet (e.g. ad libitum): standard diet (Ssniff K 4) once per day in the morning
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3°C
- Humidity (%): approx. 50%
- Air changes (per hr): Approx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illimination from 6 to 18 hours CET


IN-LIFE DATES: From: To: No data
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL

Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorso lateral area of the trunk
- % coverage: 6 cm2
- Type of wrap if used: a semi-occlusive dressing (Fixomull - Stretch Klebevlies)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with water
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: not reversible at day 14, score of 1
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: not fully reversible at day 14, score of 1
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24,48, 72h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: not fully reversible at day 14, score of 1
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Other effects:
no data

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score:

Max. score:

24 h

2/2/2 

 0/0/0 

48 h

2/2/2 

 0/0/0 

72 h

2/2/2 

 0/0/0 

Average 24h, 48h, 72h

 2.0/2.0/2.0

 0.0/0.0/0.0

Reversibility*)

NC

 C

Average time (unit) for reversion

NC

 -

NC: not completely reversible C: completely reversible

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, DESMODUR BL 3175 is classified as irritating to the skin according to the criteria of the Annex VI of the Directive
67/548/EEC and the Annex I of the CLP Regulation (EC) N°( 1272-2008).
Executive summary:

In a primary dermal irritation study conducted according to the OECD 404 guideline in compliance with GLP, 3 adult albino rabbits NZW were dermally exposed to 0.5 mL of Desmodur BL 3175 for 4 hours to 6% of the dorso lateral area of the trunk. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were observed for 14 days. Irritation was scored by the DRAIZE scale. The skin reactions were assessed at 1, 24, 48, 72 hours, 7 and 14 days after removal of the dressing. The mean individual scores were calculated across 3 scoring times at 24, 48 and 72 hours after patch removal, for each animal.

The mean individual scores were 2.0/2.0/2.0 for erythema and 0.0/0.0/.0./ for edema. At the end of the observation period, the animals scores for erythema at Day 14 were 1.0/1.0/1.0, not completely reversible.

Under the test conditions, DESMODUR BL 3175 is classified as irritating to the skin according to the criteria of the Annex VI of the Directive 67/548/EEC and to the Annex I of the CLP Regulation (EC) N°( 1272-2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
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:
other: Well conducted guideline study, GLP, no deviations.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult
- Weight at study initiation: animal 1=2.9 kg; animal 2=3.0 kg; animal 3=2.8 kg
- Housing: individually housed in stainless steel cages
- Diet (e.g. ad libitum): standard diet (Ssniff K 4) once per day in the morning
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3°C
- Humidity (%): approx. 50%
- Air changes (per hr): Approx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illimination from 6 to 18 hours CET


IN-LIFE DATES: From: To: No data
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:
0.1 mL of the test substance was instilled into the conjunctival sac of one eye of each animals after gently pulling the lower lid away from the eyeball,
the lids were then gently held together for about one second.
Observation period (in vivo):
The animals were observed at 1, 24, 48, 72 hours and 7, 14 and 21 days after instillation of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiological NaCl solution .
- Time after start of exposure: 24 hours after the instillation of the test substance


SCORING SYSTEM: The sign of cornea, iris, conjunctivae and discharge were recorded as describe by Draize scale; the aqueous humour as described by Mcdonald and Shadduck.


TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48,72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
No irritant effect has been observed and recorded on the eye until day 21.
Other effects:
No aqueous humour discharge has been observed and recorded in any animals.

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 0

Max. score: 0

Max. score: 0

Max. score: 0

24 h

0/0/0

0/0/0

0/0/0

0/0/0

48 h

 0/0/0

 0/0/0

0/0/0 

 0/0/0

72 h

0/0/0 

0/0/0 

0/0/0 

0/0/0 

Average 24h, 48h, 72h

0.0/0.0/0.0

0.0/0.0/0.0

0.0/0.0/0.0

0.0/0.0/0.0

Reversibility*)

-

 -

-

-

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, DESMODUR BL 3175 is not classified as irritating to eye according to the criteria of the Annex VI of the Directive 67/548/EEC and to the Annex I of the CLP Regulation (EC) N°( 1272-2008).
Executive summary:

In a primary eye irritation study, conducted according to the OECD 405 guideline, in compliance with GLP, 0.1 mL of Desmodur BL 3175 was instilled into the conjunctival sac of 3 adult albino NZW rabbits. Treated eyes were washed with physiological NaCl solution 24 hours after instillation of the test substance. Animals were then observed for 21 days. Irritation was scored by the method of Draize and aqueous humour discharge by the method of Mcdonald and Shadduck.

The mean individual scores were 0.0 for cornea, iris, conjunctivae and chemosis. No aqueous humour discharges was observed.

Under the test conditions, DESMODUR BL 3175 is not classified as irritating to the eye according to the criteria of Annex VI to the Directive 67/548/EEC and to the criteria of Annex I to the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a dermal irritation study with DESMODUR BL 3175, conducted according to OECD 404 guideline in compliance with GLP (Märtens, 1990), 3 healthy adult rabbits were exposed to 0.5 mL of DESMODUR BL 3175 to 6% of the dorso-lateral area of the trunk covered with a semi-occlusive dressing for 4 hours. Mean individual scores (within 24, 48 and 72 hours) were 2.0/2.0/2.0 for erythema and 0.0/0.0/0.0 for oedema. At the end of the observation period, the scores for erythema at Day 14 were 1.0/1.0/1.0, not completeley reversible.

In an eye irritation study conducted according to OECD 405 guideline in compliance with GLP (Märtens, 1990)

, 3 adult albino rabbits were instilled into the conjunctival sac with DESMODUR BL 3175. Mean individual scores were 0.0 for cornea, iris, conjunctivae and chemosis.

In a sensory irritation study in which the protocol is based on the ASTM method designed E981-84, 4 male mice per dose were exposed to aerosol of DESMODUR BL 3175 at 0, 335, 486, 821 and 1459 mg/m3 aerosol for 3 hours according to an exposure technique which met the requirements of the OECD 403 guideline. The RD50 was 1450 mg/m3. No mortality has been observed up to the highest dose. Slight bradypnea has been observed at the highest dose. No body weight and no indications of specific organ changes has been observed. The pulmonary function test showed that the preparation in aerosol induced a concentration-dependant decrease in the respiratory rate.


Effects on skin irritation/corrosion: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

As signs of irritation were observed in a dermal irritation study with DESMODUR BL 3175 (75% of HDI Trimer MEKO blocked in 25% of solvent naphta 100) conducted according to OECD 404 guideline in compliance with GLP, DESMODUR BL 3175 is classified as irritating to the skin according to the Annex I of the CLP Regulation N° (1272/2008) and to the Annex VI of the Directive 67/548/EEC. Solvent naphta (64742 -95 -6) was evaluated in the OECD/HPV programm; it was shown to induce slight to moderate skin irritation. Having 25% of the solvent in the preparation it is not likely it is the unique inducer of irritation. Therefore according to an expert judgment HDI Trimer MEKO blocked is likely classified as irritating to skin.

As no signs of irritation to eye were observed in an eye irritation study conducted according to OECD 405 guideline in compliance with GLP, DESMODUR BL 3175 (75% of HDI Trimer MEKO blocked in 25% of solvent naphta 100)

is not classified as irritating to eyes according to the Annex I of the CLP Regulation N° (1272/2008) and to the Annex VI of the Directive 67/548/EEC. Therefore, according to an expert judgment, considering that the scores are all over 0, the solvent is not classified for irritancy to eye and the preparation contains about 75% of test substance, HDI Trimer MEKO blocked is not likely to be classified as irritating to the eye.

A sensory irritation study with aerosol exposure (head/nose-only) of Desmodur BL 3175 revealed a 3-hour RD50 (50 % inhibition of 

respiration) of 1450 mg/m3 air in male mice. The examinations showed that an aerosol of Desmodur BL 3175 considered as respirable has a weak but toxicologically not relevant sensory irritation potency.