Glutaral

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: see 'Remark'

Remarks:

Scientifically acceptable, well-documented study. The conduct was similar to OECD 403 but no particle size analysis was undertaken. However, within a further similar acute inhalation study performed by the same author (see BASF83/59), a particle size analysis was conducted, which revealed that 100% of the test substance applied as liquid aerosol reached the lung alveoli.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Ten male and ten female Sprague-Dawley rats per dose group were exposed to different concentrations of test material as liquid aerosol; the animals were subjected to a head-nose exposure for 4 hours. The exposure period was followed by an observation period of 14 days. During and after exposure, mortality and clinical signs of toxicity were recorded at regular time intervals. The body weight was determined prior test initiation and thereafter, on day 7 and day 14 post-exposure. Rats that died during the experiment were subjected to necropsy; those which survived were sacrificed at the end of the experiment and were also subjected to necropsy. An untreated rat collective served as control. The determination of the LC50 values was based on the Probit Analysis.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was performed

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glutaral

EC Number:

203-856-5

EC Name:

Glutaral

Cas Number:

111-30-8

Molecular formula:

C5H8O2

IUPAC Name:

glutaraldehyde

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Glutaraldehyde approx. 50% solution, poor in methanol
- Physical state: liquid
- Analytical purity: 50%
- Lot/batch No.: the test substance No. was 80/265
- Stability under test conditions: approx. 12 months

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Willi Gassner, Sulzfeld, Germany (animal breeder)
- Age at study initiation: 8 weeks
- Mean body weight of the males at study initiation: 298 +/- 35 g
- Mean body weight of the females at study initiation: 224 +/- 28 g
- Housing: animals were housed in groups of five in wire cages of Becker, type D III, without bedding.
- Diet (e.g. ad libitum): SSNIFF R complete diet for rats and mice, supplied by SSNIFF-Versuchstierdiäten GmbH (Soest, FRG), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: The test substance was offered to the animals as a liquid aerosol/air mixture

Details on inhalation exposure:

AEROSOL GENERATION, EXPOSURE SYSTEM AND PROCEDURE
- Constant amounts of test substance were supplied to a two-component atomizer by means of a metering pump;
- By means of compressed air (1.8 bar) a mixture of test substance and air (liquid aerosol) was generated, which was passed into the inhalation system;
- The inhalation system was a head-nose inhalation system INA 20, BASF AG, V ca. 55 l;
- By means of the exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of fresh air was about 10% higher (excess pressure) . This ensured that the mixture of test substance and air was not diluted by laboratory air in the breathing zones of the animals.

AIR SAMPLING FOR ANALYSIS OF TEST MATERIAL CONCENTRATIONS, METHOD FOR ANALYTICAL VERIFICATION
- A sampling apparatus consisted of 2 impingers connected in series and a downstream fritted glass flask was used;
- The sampling sites were Inmediately adjacent to the animal noses;
- One sample per concentration group was collected every hour;
_ The sampling flow was 1.25 m/s, and the sample amount reached up to 50 litres;
- The analytical measurement of the test material concentrations in the collected samples was based on gas-chromatography.

PARTICLE SIZE ANALYSIS:
No particle size analysis was undertaken within the present study. However, within a further similar acute inhalation study performed by the same author (see BASF83/59), a particle size analysis was conducted, which revealed that 100% of the test substance applied as liquid aerosol reached the lung alveoli.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

For details, see above

Duration of exposure:

4 h

Concentrations:

Nominal: 0.23, 0.41, 0.53, 0.68 and 0.9 mg/l
Measured: 0.10, 0.18, 0.28, 0.39 and 0.44 mg/l

No. of animals per sex per dose:

10 animals/sex/group

Control animals:

yes

Details on study design:

- The animals were subjected to a head-nose exposure for 4 hours; this was followed by an observation period of 14 days;
- The rats were observed during exposure and over a period of 14 days for mortality (daily) and clinical signs of toxicity (each workday
- Body weights were recorded at test initiation, after 7 days and at the end of the observation period;
- Animals that died during the observation period were subjected to necropsy and gross pathological examination,
- Animals that survived were sacrificed at the end of the exposure period by means of CO2 for necropsy and gross pathology.
- An untreated rat collective served as control.

Statistics:

The determination of the LC50 value was based on Probit Analysis according to Finney DJ, Cambridge University Press, 3rd edition, 1971.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.28 - 0.39 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

0.35 mg/L air (analytical)

95% CL:

0.3 - 0.39

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

0.28 mg/L air (analytical)

95% CL:

0.22 - 0.29

Exp. duration:

4 h

Mortality:

- in the control group, all animals survived;
- in the 0.18 mg/l air group, mortality was 4/20, i.e. 20%;
- in the 0.28 mg/l air group, mortality was 4/20, i.e. 20%;
- in the 0.39 mg/ l air group, mortality was 14/20, i.e. 70%;
- in the 0.44 mg/l air group, mortality was 19/20, i.e. 95%.

Clinical signs:

other: During the exposure period vigorous attempts to escape, wiping of the snout, lid closure, and aqueous or red discharge from eyes and noses were observed. During the post-exposure period whooping or gasping respiration with rasping sounds during inspiratio

Body weight:

After 7 days, the body weights of the treated males were clearly impaired compared to controls; After 14 days this impairment still was observed in the 0.28 and the 0.39 mg/l groups. For the females, the body weight in the 0.39 mg/l group was impaired during the whole observation period; the body weight of the 0.28 mg/l group only was affected after 7 days.

Gross pathology:

- Necropsy of the animals that died during the experiment revealed acute congestion, pronounced emphysema of the lungs as well as edematization and infarctoid hyperemia.
- Necropsy of the surviving animals, which were sacrificed at the end of the observation period, showed no pathological abnormalities.

Any other information on results incl. tables

Details on mortality:

Applied Test Con. (mg/l)	Mortality (males)	Mortality (females)	Mortality (both sex)
0.10	0/10	0/10	0/20 (0%)
0.18	1/10 (d14)*	3/10 (d1-d2)	4/20 (20%)
0.28	1/10 (d1)	3/10 (d2-d7)	4/20 (20%)
0.39	7/10 (4h-d2)	7/10 (4h-d2)	14/20 (70%)
0.44	9/10 (4h-d1)	10/10 (4h-d14)	19/20 (95%)

*, Time of death after dosing (h, hours; d, days)

Details on mean body weights/sex/group:

Applied Test Con. (mg/l)	Initially		After 7 days**		After 14 days**
	Males	Females	Males	Females	Males	Females
0*	307 g	230 g	340 g	240 g	367 g	249 g
0.10	289 g	228 g	324 g	238 g	376 g	252 g
0.18	304 g	224 g	319 g	238 g	360 g	246 g
0.28	305 g	222 g	320 g	228 g	343 g	240 g
0.39	287 g	211 g	316 g	211 g	321 g	208 g
0.44	304 g	232 g	285 g	168 g	334 g	-***

*, Control group of 90 animals/sex.

**, The mean body weight refers to the surviving rats.

***, No survivors.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

- Acute inhalation toxicity (rat, 4 h exposure): 0.28 < LC50 < 0.39 mg/L air (50% glutaraldehyde)