glyoxal … %; ethandial … %

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:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

2008

Reference 3

Reference Type:

other: TSCAT Document

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC Directive 79-831, Annex V, Part 8: Methods For The Determination Of Toxicity, 4.1.2 Acute Toxicity Inhalation

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glyoxal

EC Number:

203-474-9

EC Name:

Glyoxal

Cas Number:

107-22-2

Molecular formula:

C2H2O2

IUPAC Name:

oxalaldehyde

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Code HF 0001
- Purity test date: 21. 12. 1983

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: storage at 22 °C in the dark recommended

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF-Zucht
- Age at test initiation: 8 to 10 weeks
- Weight at study initiation: males, 186 g (175 – 210 g); females, 189.5 g (171 – 207 g)
- Fasting period before study: 16 hours prior and 2 hours after treatment
- Housing: five animals per cage, in Makrolon cages type 4
- Diet (e.g. ad libitum): rat feed (Rattendiaet Altromin 1324), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Air changes (per hr): housing in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The test substance was conducted at a constant rate through a permanent infusion apparatus into a special injector, where an air stream was entered by a compressor at 4 bar. The flow rate of the air stream was maintained constant at 800 L/hour (rotameter). A primary aerosol was so generated in a vessel and was conducted through an ascending tube into the exposure chamber; due to the ascending tube, only small aerosol particles, defined as secondary aerosol, reached the chamber from the top. The aerosol/air mixture was evacuated at the bottom of the chamber through a vacuum system with cotton filter and a 10% sodium hydroxide solution, at a rate of 1100 l/hour.

PARTICLE SIZE DISTRIBUTION
The test concentrations of aerosol in the exposure chamber were determined gravimetrically.
The size distribution of the test substance particles was determined by means of the particle counting system, model 225 (Kratel GmbH, Stuttgart, Germany). The mass median aerodynamic diameter (MMAD) was measured for the following size classes:
0.3 – 0.49 µm, 0.5 – 1.49 µm, 1.5 – 2.01 µm, 2.02 – 2.99 µm, 3.0 – 3.99 µm, 4.0 – 4.99 µm, 5.0 – 5.99 µm, and > 6.0 µm.

MONITORING OF CHAMBER PARAMETERS
During exposure, the CO, CO2, and O2 contents as well as the relative humidity and the temperature in the exposure chamber were measured.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

determination of the test substance was based on the use of an UV-detector (405 nm) after reaction with 2-hydrazono-2,3-dihydro-3-methylbenzthiazole hydrochloride in aqueous solution.

Duration of exposure:

4 h

Concentrations:

- The respective test concentrations were 2.20, 2.60 and 2.70 mg of unchanged test substance/l air (determined analytically).
- The corresponding application volumes were 45, 60 and 90 mL/hour, respectively.

No. of animals per sex per dose:

Five animals per sex and group were used

Control animals:

no

Details on study design:

- During exposure the animals were observed for clinical symptoms indicative of toxicity and for mortality;
- The treatment was followed by a 14-day post-exposure observation period; during this period the animals were regularly observed for clinical symptoms and mortality, and their body weights were recorded on day 2, 3, 4, 7 and 14. Dead animals were subjected to necropsy as soon as possible; the surviving animals were sacrificed at the end of the observation period for the purpose of necropsy.

Statistics:

The LC50 was determined by means of Probit Analysis.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.44 mg/L air (analytical)

95% CL:

2.23 - 2.59

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

2.47 mg/L air (analytical)

95% CL:

2.13 - 2.75

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

2.41 mg/L air (analytical)

95% CL:

2.04 - 2.67

Exp. duration:

4 h

Mortality:

-Mortality was 20%, 50% and 100% in each of the 2.20, 2.60 and 2.70 mg/L  group, respectively. Most cases of death occurred within the first day following treatment.
- In the 2.20 mg/L group, 2 animals died; 1 male was found dead after 18.5 hours following treatment, whereas 1 female was found dead on day 2.
- In the 2.60 mg/L group, 5 animals died; there from, 2 males and 2 females were found dead on day 1 post treatment whereas 1 female died on day 9.
- In the 2.70 mg/L group, all animals except for one female died within 1 day following treatment; the last female died on day 3 post treatment.

Clinical signs:

other: - Symptoms of toxicity were seen in all groups and comprised irregular breathing, reddish nasal discharge, intermittent respiration, gasping, noisy breathing, narrowed eyelids, sneezing, retracted flanks, piloerection, prone position, and drowsiness; - Th

Body weight:

For both sexes, a temporary loss in body weight was observed after 2 days following treatment; however, this effect was reversible within 7 days. For details, see table below.

Gross pathology:

Dead animals: both dead animals of the 2.20 mg/L group as well as 2 dead males and 2 dead females of the 2.70 mg/L group were autolytic at necropsy. Necropsy of the remaining animals that died revealed dark red lungs with foamy content.
Sacrificed animals: necropsy of the animals that were sacrificed at the end the observation period revealed no abnormalities.

Other findings:

- Particle size analysis demonstrated that for each test concentration, the respirable particle fraction < 3.0 µm was > 80% (i.e. respectively ca. 84, 81 and 85%).
- For details on monitored parameters and particle size analysis, see tables below.

Any other information on results incl. tables

Body weight data:

2.20 mg/L  group	Males	Females
Initial  body weight range	176-188 g (N=5)	171-182 g (N=5)
Body weight range, day 2	147-160 g (N=4)	149-163 g (N=5)
Body weight range, day 3	142-159 g (N=4)	157-165 g (N=4)
Body weight range, day 4	153-162 g (N=4)	158-164 g (N=4)
Body weight range, day 7	180-193 g (N=4)	173-183 g (N=4)
Body weight range, day 14	230-250 g (N=4)	195-205 g (N=4)
2.60 mg/L  group	Males	Females
Initial  body weight range	177-192 g (N=5)	178-196 g (N=5)
Body weight range, day 2	167-174 g (N=3)	156-178 g (N=3)
Body weight range, day 3	170-173 g (N=3)	149-163 g (N=3)
Body weight range, day 4	179-182 g (N=3)	147-160 g (N=3)
Body weight range, day 7	214-219 g (N=3)	134-154 g (N=3)
Body weight range, day 14	251-262 g (N=3)	175, 178 g (N=2)
2.70 mg/L  group	Males	Females
Initial  body weight range	175-210 g (N=5)	191-207 g (N=5)
Body weight ranges	Not applicable because of mortality	Not applicable because of mortality

Exposure chamber, monitored parameters:

Parameters	Monitored values in the exposure chamber for each test group
	2.20 mg/L	2.60 mg/L	2.70 mg/L
CO (ppm)	2	0	2 – 4
CO2 (ppm)	2900 – 3500	2000 – 3100	2100 – 3100
O2 (%vol.)	19.6 – 19.7	20.1	20.4 – 20.5
Temperature (°C)	23.6 – 24.2	23.0 – 24.2	23.3 – 23.9
Rel. humidity (%)	81.6  – 94.0	100	98.5 - 100

Particle size analysis, results:

Particle size interval (µm)	Particle fraction (%)
	2.20 mg/L	2.60 mg/L	2.70 mg/L
0.3 – 0.49	25.1	31.1	25.3
0.5 – 1.49	33.9	29.3	32.1
1.5 – 2.01	14.8	11.8	16.1
2.02 – 2.99	9.8	9.1	11.7
3.0 – 3.99	4.8	8.9	5.9
4.0 – 4.99	4.0	4.5	5.2
5.0 – 5.99	2.2	2.8	2.6
> 6.0	5.5	6.5	5.0

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria