Hexamethylene diisocyanate, oligomerisation product, blocked with 2-butanone oxime

Acute Toxicity: inhalation

Administrative data

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

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Desmodur BL 3175

IUPAC Name:

Desmodur BL 3175

Details on test material:

- Name of test material (as cited in study report): Desmodur BL 3175
- Physical state: very viscous liquid
- NCO content: 0.04 %
- Composition: ca. 75 % polyisocyanurate blocked with 2-butanonoxime and ca. 25 % solventnaphtha 100
- Lot/batch No.: 214
- Storage condition of test material: room temperature, darkness

Test animals

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

Administration / exposure

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).

Results and discussion

Preliminary study:

No data

Effect levels

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.

Any other information on results incl. tables

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)

Applicant's summary and conclusion

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.