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Administrative data

Description of key information

HDI Trimer MEKO blocked  is not classified according to an expert judgment as LD50 was found higher than 1500 mg/kg bw for acute oral toxicity 
without deaths and any signs of toxicity.
HDI Trimer MEKO blocked is not likely to be classified for acute dermal toxicity as LD50 is above 2000 mg/kg bw (LD50 above 2667 mg/kg bw for
DESMODUR BL 3175).
HDI Trimer MEKO blocked is not classified for acute inhalation toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-conducted GLP study, according to guideline
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
other: Richtlinie 84/449/EWG, test protocol corresponds to OECD 401, LImit Test
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: males appr. 8 weeks, females appr. 10 weeks
- Weight at study initiation: males mean 185 g, females mean 175 g
- Fasting period before study: 16 hours
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 10 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
limit test, no statistics required
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: dose was tolerated without mortalities, body weight changes or clinical signs of toxicity
Mortality:
None
Clinical signs:
None
Body weight:
Not influenced by treatment
Gross pathology:
No unusual lesions were noted in any of the animals
Other findings:
No other findings

Number of animals dead [and with evident toxicity] [and time range within which mortality occurred

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

2000

0

0

0

-

0

0

0/10

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

In an acute oral toxicity study, conducted according to OECD 401 guideline, in compliance with GLP, 10 Wistar rats (5 by sex) were given a single oral dose of Desmodur BL 3175 in propylene glycol (10 ml/kg bw) at dose of 2000 mg/kg bw.

The LD50 in rats was determined > 2000 mg/kg bw for the preparation. This dose was well-tolerated without mortalities, body weight changes or clinical signs of toxicity.

Therefore, DESMODUR BL 3175 is not classified for acute oral toxicity according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N°( 1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 500 mg/kg bw
Quality of whole database:
GLP study in accordance with OECD 401 guideline

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-conducted GLP study, according to guideline
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 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann (Borchen, Germany)
- Strain: Bor: WISW (SPF-Cpb)
- Age at study initiation: 2-3 months
- Housing: 5 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12


Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: xylene
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel inhalation chambers from Rhema Labortechnik (Hofheim, Germany)
- Exposure chamber volume: about 7 l
- Method of holding animals in test chamber: Plexiglas exposure tubes applying a directed-flow nose/head-only exposure principle
- Source and rate of air: compressed air was supplied by Boge compressors; about 86 air exchanges per hour
- Method of conditioning air: air was conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer
- System of generating particulates/aerosols: with the help of a nozzle and conditioned compressed air a 75 % solution of the test substance in xylene up to a nominal concentration of 50000 µl/m3 air was nebulized in the pre-separator of the inhalation chamber
- Method of particle size determination: particle analyses were performed using a BERNER cascade impactor; the individual impactor stages were evaluated gravimetrically
- Treatment of exhaust air: the exhaust air was purified via cotton-wool filters; these filters were disposed of by Bayer AG
- Temperature, humidity: 20-22 °C, 18-50 % (rel. humidity)


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis
- Samples taken from breathing zone: yes


VEHICLE
- Concentration of test material in vehicle (if applicable): 75 %
- Justification of choice of vehicle: due to the viscosity of the test item spraying as aerosol without addition of xylene was technically not possible
- Purity: no data


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 82-99 % of particles were <= 5 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 2.25 µm (GSD: 2.06) for test conc. 2757 mg/m3 air



Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean analytical concentrations: 0, 343, 543, 1573 and 2757 mg/m3
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs were examined several times on the day of exposure and twice daily therafter; body weights were measured before exposure, on days 3 and 7, and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: reflexes
Statistics:
Calculation of the LC50: If calculation of a median lethal concentration (LC50) is possible, it is performed by computer (HP 3000) according to the
method of AP. Rosiello, I.M. Essigmann, and G.N. Wogan (1977) as modified by Pauluhn (1983). This method is based on the maximurn-likelihood method of C.I. Bliss (1938).
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 757 mg/m³ air
Exp. duration:
4 h
Mortality:
Aerosol concentrations up to 2757 mg/m3 air were tolerated without mortality (details see table 1).
LC50>1551 mg/m3 for the test substance which corresponds to 1396 mg/m3 or 1.396 mg/L when considering the respirable particules (<5µm).
Clinical signs:
other: All animals exposed to 343 and 543 mg/m3 air of the test substance or to control group I (3334 µl xylene/m3 air) revealed no clinical signs. At 1573 mg/m3 air reduced motility, staggered gait, bradypnea and piloerection were observed. From the first post-
Body weight:
No effects on body weight were observed in the post-observation period at exposure concentrations of 343 mg/m3 air and above.
Gross pathology:
No indications of specific organ changes were seen in exposed animals compared to control groups.
Other findings:
No test substance-related changes on reflexes were observed between day 1 and day 3 of the post-observation period.

Table 1: Acute inhalation toxicity (aerosol) of Desmodur BL 3175

 Sex Analytical concentration (mg/m3) Toxicological results  Onset and duration of signs  Particle <= 5 µm (%)
 male

0 (control I *)

0 / 0 / 5

 --- --- 
    0 (control II **)

0 / 5 / 5

4h - 6h --- 
   343

0 / 0 / 5

--- 

97 

   543

0 / 0 / 5 

---

99

  1573

0 / 5 / 5

4h - 6h  82
   2757 0 / 5 / 5 4h - 6h  90
 female 0 (control I *)

0 / 0 / 5 

 --- --- 
    0 (control II **) 0 / 5 / 5  4h - 6h  --- 
  343 0 / 0 / 5 ---  97 
  543 0 / 0 / 5 --- 99 
  1573  0 / 5 / 5 4h - 6h 82
  2757 0 / 5 / 5 4h - 6h  90

Toxicological results:

number of dead animals / number of animals with signs after cessation of exposure / number of animals exposed

*   Control group I (3334 µl xylene / m3 air)

** Control group II (10000 µl xylene / m3 air)

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

In an acute inhalation toxicity study, conducted according to OECD TG 403 guideline, in compliance with GLP, groups of Wistar rats (5 by sex) were exposed by inhalation route to Desmodur BL 3175 (75%) in xylene for 4 hours to nose/head only at aerosol concentrations of 0, 343, 543, 1573 and 2757 mg/m3. Animals were then observed for 14 days.

The inhalation LC50 in rats of both sexes was determined to be > 2757 mg/m3 air.

The maximum technically producible concentration was of 2757 mg/m3 which is below to the limit of classification (5 mg/L).

Moreover the vapor pressure of the test substance in Solvessonaphta 100 (75/25) is about 5hPa at 20°C which implies that the preparation is slightly volatile under normal conditions of use. This maximum technically producible concentration of 2757 mg/m3 air was tolerated without deaths and signs of toxicity.The observed symptoms are seen in a causal context with the used solvent xylene.

Therefore, according to Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N°( 1272-2008), DESMODUR BL 3175 is not classified for acute inhalation toxicty.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 068 mg/m³
Quality of whole database:
GLP study in accordance with OECD 403 guideline

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restriction, GLP guideline study
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 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan, GmbH
- Age at study initiation: 9-13 weeks
- Weight at study initiation: male: 272-286g; female: 233-255g
- Fasting period before study: no fasting period
- Housing: caged individuallyin polycarbonate cageson low dust wood granulate bedding
- Diet (e.g. ad libitum): standard diet "Provimi kliba 3883 PM S15 Maus/Ratte haltung, Kaiseraugst Switzerland
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 5°C
- Air changes (per hr): approx. 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours rythm


IN-LIFE DATES: From: To: No data
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: approx 10% of the body surface area
- Type of wrap if used: a gauze-layer (6.0 cm * 5.0 cm) of a Cutiplast* steril coeated with air-tight Leukoflex*


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the are was rinsed with tepid water using soap and gently aptting the area dry
- Time after start of exposure: after appro. 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): males: 18.1-19.1 mg/cm2; females: 15.5-17.0 mg/cm2
- Concentration (if solution):



VEHICLE: no vehicle
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24 hours
Doses:
2667 mg/kg bw of DESMODUR BL 3175 SN.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations and mortality: several times on the day of application and at least once a day during observation period
Weight:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 667 mg/kg bw
Mortality:
No mortality
Clinical signs:
No clinical signs observed in male animals. Partial reddening, encrustration and formation of scale of the treatment area were observed in females.
Body weight:
No toxicologically significant effects on body weight or body weight development in males and females. The slight decrease in body weight gain in
females the first week is assumed to be caused by the stress of the application procedure.
Gross pathology:
No particular findings.
Other findings:
No data

Dose (mg/kg bw)

Toxicological results*

Occurrence of signs

Time of death

Mortality (%)

Male     2000**

0 / 0 / 5

-

-

0

Female 2000**

0 / 5 / 5

2d – 13d

-

0

*number of animals which died spontaneously and/or were sacrificed in moribund state / number of animals with signs of toxicity / total number of animals used per groups used per group

** expressed as HDI Trimer MEKO blocked

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, DESMODUR BL 3175 SN (75% HDI Trimer MEKO blocked in 25% solvent naphta 100) is not classified for acute
dermal toxicity according to the criteria of the CLP regulation (EC) N°(1272/2008) and the Annex VI to the Directive 67/548/EEC.
Executive summary:

In an acute dermal toxicity study, performed according to OECD 402, in compliance with GLP, 5 rats Wistar by sex were applied with DEMSODUR BL 3175 SN (75% HDI Trimer MEKO blocked in 25% solvent naphta 100) at a concentration of 2667 mg/kg bw.

No mortality, no clinical signs in male, no effect on body weight have been observed. Artial reddening, encrustration and formation of scale of the treatment area were observed in females.

LD50>2667 mg/kg bw .

DESMODUR BL 3175 SN is not classified for acute dermal toxicity according to the criteria of hte CLP regulation (EC) N°(1272/2008) and the Annex VI to the Directive 67/548/EEC.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP study in accordance with OECD 402 guideline

Additional information

DESMODUR BL 3175 was tested for acute oral toxicity (Bomhard, 1991) according to the OECD 401 guideline in a limit test and in compliance with GLP. Groups of rats (5 by sex) were given a single oral dose of DESMODUR BL 3175 in propylene glycol at 2000 mg/kg bw.

As HDI Trimer MEKO blocked is present at a percentage of 75% in the preparation, the maximum dose tested for HDI Trimer MEKO blocked is therefore about 1500 mg/kg bw.

DESMODUR BL 3175 was tested for acute dermal toxicity (Gillessen, 2010) according to the OECD 402 guideline in a limit test and in compliance with GLP. Groups of rats (5 by sex) were applied with DEMSODUR BL 3175 SN (75% HDI Trimer MEKO blocked in 25% solvent naphta 100) at a concentration of 2667 mg/kg bw, which means at 2000 mg/kg bw of HDI Trimer MEKO blocked.

DESMODUR BL 3175 was tested for acute inhalation toxicity (Pauluhn,1990) according to the OECD 403 guideline in compliance with GLP. The assay was conducted in groups of rats (5 by sex) by inhalation route at concentrations of 0, 343, 543, 1573 and 2757 mg/m3 air of aerosol for 4 hours. The maximum technically concentration producible was 2757 mg/m3 of air.

Justification for classification or non-classification

Acute oral toxicity

LD50 is 2000 mg/kg bw for DESMODUR BL 3175 which corresponds to 1500 mg/kg bw considering HDI Trimer MEKO blocked. This dose was well-tolerated without mortalities, body weight changes or clinical signs of toxicity.

DESMODUR BL 3175 SN is not classified for acute oral toxicity according to the criteria of the CLP regulation (EC) N°(1272/2008) and the Annex VI to the Directive 67/548/EEC.

As no mortalities, no clinical signs, no unsual lesions occured and no toxic effects appeared at this tested concentration it is likely that the LD50 for HDI Trimer MEKO blocked is above 2000 mg/kg bw.

Therefore, according to an expert judgment, HDI Trimer MEKO blocked is not considered to be classified for acute oral toxicity.

Acute dermal toxicity

LD50>2667 mg/kg bw of DESMODUR BL 3175 SN.

No mortality, no clinical signs in male, no effect on body weight have been observed. Artial reddening, encrustration and formation of scale of the treatment area were observed in females.

DESMODUR BL 3175 SN is not classified for acute dermal toxicity according to the criteria of the CLP regulation (EC) N°(1272/2008) and the Annex VI to the Directive 67/548/EEC.

Therefore, according to an expert judgement, it is unlikely that HDI Trimer MEKO blocked would be considered to be classified for acute dermal toxicity.

Acute inhalation toxicity

LC50 is above 2,757 mg/L air of DESMODUR BL 3175 which corresponds to 2,068 mg/L air of HDI Trimer MEKO blocked

This maximum technically producible concentration of 2,757 mg/L air was tolerated without deaths and signs of toxicity.The observed symptoms are seen in a causal context with the used solvent xylene.

DESMODUR BL 3175 SN is not classified for acute inhalation toxicity according to the criteria of the CLP regulation (EC) N°(1272/2008) and the Annex VI to the Directive 67/548/EEC.

Therefore according to expert judgment, it is unlikely that HDI Trimer MEKO blocked is classifed for acute inhalation toxicity.