HDI oligomers, biuret

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report which meets basic scientific principles; the test conduct was similar to the OECD TG 403.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

28182-81-2

Molecular formula:

Unspecified (UVCB substance)

Constituent 2

Reference substance name:

HDI oligomers, biuret

EC Number:

939-340-8

Cas Number:

28182-81-2

Molecular formula:

(C8H12N2O2)n

IUPAC Name:

HDI oligomers, biuret

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 20 male and 20 female animals
- Source: Central Institute for breeding of Laboratory Animals TNO, Zeist, the Netherlands
- Mean weight at study initiation: males 172 g, females 143 g.
- Diet: ad libitum (Institute' s stock diet for rats)
- Water: ad libitum (bottled unfluoridated tap water)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C +/-1
- Humidity (%): 30-70%

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: H 1000 multitiered inhalation chamber (Hazleton Systems Inc., USA)
- Exposure chamber volume: 2.3 m³
- Method of holding animals in test chamber: individually, whole body exposure
- System of generating particulates/aerosols: 2 steel/glass air nebuliser, equipped with a baffle for separation of large particles (thermostated at about 70°C). Deposited test substance was not re-circulated through the nebuliser, which is usual for this type of generator. Upon entering the exposure chamber, additional air was mixed with the aerosol resulting in a total air flow of 4-11 m³/hour.
- Method of particle size determination: The particle size distribution was determined by means of a cascade impactor.
- Temperature, humidity, pressure in air chamber: 19.5 ± 1°C, 30-70%.

TEST ATMOSPHERE
- Brief description of analytical method used:
1. Gravimetry: by a glass fiber filter (type SM 134 00 from Sartorius). The first sample was taken 45 minutes after start of the exposure and subsequent samples were taken at about one hour intervals.
2. Spectrophotometry:
a. Calculation from the oil-red concentration determined by spectrophotometry after sampling of the test atmosphere by means of a G-4 filter and an impinger. Samples were taken simultaneously with those indicated under 1.
b. Calculation from the oil red concentration, determined by spectrophotometry after sampling of the test atmosphere by means of a cascade impactor during each exposure period one such a sample was taken.
3. HPLC: Calculation from the monomeric HDI concentration determined by HPLC after sampling of the test atmosphere by means of an impinger. The first sample was taken 60 minutes after the start of the exposure and subsequent samples were taken at approximate one hour intervals.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: in all samples about 100 % of the particles had a diameter smaller than 5 µm.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Group 465 mg/m³: 1.8µm/1.9µm
Group 413 mg/m³: 1.8µm/1.9µm
Group 301 mg/m³: 1.8µm/1.8µm
Group 256 mg/m³: 1.7µm/1.6µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimety, HPLC of monomer, spectrophotometry

Duration of exposure:

4 h

Concentrations:

values obtained by gravimetry: 465 mg/m³, 413 mg/m³, 301 mg/m³, 256 mg/m³

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Groups of male and female rats were exposed one single time for a period of four hours to an atmosphere in which a specific concentration of test substance aerosol was maintained.
During the exposure and the observation period the animals were controlled for mortality and reactions to treatment daily. Observed abnormalities were recorded. Body weights were recorded at days 0, 1, 2, 4, 7 and 14.
Gross pathology was performed on survivors and animals which were found dead during the study period.

Statistics:

Probit analysis method of Finney.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

402 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

244 - 560

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

423 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

225 - 797

Exp. duration:

4 h

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

388 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

177 - 848

Exp. duration:

4 h

Mortality:

Mortality was 50% at 465 mg/m³, 70% at 413 mg/m³, 30% at 301 mg/m³ and 0% at 256 mg/m³
No mortality occurred during exposure; all animals that died, died within 2 days after termination of the exposure period.

Clinical signs:

other: During the exposure period the animals were quiet and kept their eyes closed. No abnormalities were observed during the observation period. The fur of the back skin of the animals was slightly pink coloured at the end of the exposure period.

Body weight:

Both males and females lost body weight or gained hardly weight during the first 24 hours of the observation period. After day 2, body weight gain turned back to normal.

Gross pathology:

Gross examination of animals that died during the experimental period revealed hydrothorax and/or haemorrhagic lungs. Haemorrhagic lungs were observed also in one male rat of the 465 mg/m³ group that was killed at the end of the observation period.
No treatment related abnormalities were observed in the animals of the other groups, killed at the end of the observation period.

Any other information on results incl. tables

Analytical results:

Data obtained by gravimetry were approx. 25% higher than those obtained by spectrophotometry.

In all samples about 100 % of the particles had a diameter smaller than 5 µm.

Table 1: Mean concentration of test substance in test atmospheres [mg/m3], particle size distribution MMAD +/-GD [µm] and mortality [%]:

[mg/m3]	Gravimetry	Spectophotometry		HPLC	Particle size distribution	Mortality
treatment group		G4 filter	cascade impactor
A	465	403	387	291	1.8 +/-1.9	50
B	413	308	313	317	1.8 +/-1.9	70
C	256	193	240	not detectable	1.7 +/-1.6	0
D	301	238	313	not detectable	1.8 +/-1.8	30