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Toxicological information

Acute Toxicity: inhalation

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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: Guideline study, performed under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Allyl alcohol
EC Number:
203-470-7
EC Name:
Allyl alcohol
Cas Number:
107-18-6
Molecular formula:
C3H6O
IUPAC Name:
prop-2-en-1-ol
Details on test material:
Lot No.: 02109PE
Purity: 99.4%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina, USA
- Age at study initiation: 11-12 weeks old
- Weight at study initiation: 336g - 443g for males; 207g - 253g for females
- Fasting period before study:
- Housing: Stainless steel and wire-mesh cages suspended above a cage-board.
- Diet (e.g. ad libitum): PMI Nutrition International LLC, Certified Rodent LabDiet (R) 5002 ad libitum
- Water (e.g. ad libitum): Reverse osmosis-treated (on-site) drinking water ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12-hour light / 12-hour dark

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: nitrogen
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass whole-body exposure chambers
- Exposure chamber volume: 500 litres
- Source and rate of air: Chamber supply air from a HEPA- and charcoal-filtered, temperature- and humidity-controlled source.
- System of generating particulates/aerosols: Test substance vapours were generated using a 125-mL stem frit, 250-mL bottom frit and/or 500-mL bottom frit bubbler-type vaporization system
- Treatment of exhaust air: charcoal and HEPA filtration
- Temperature, humidity, pressure in air chamber: Temperature: 20 - 24 degrees C; humidity: 30-70%

TEST ATMOSPHERE
- Brief description of analytical method used: Gas Chromatography
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC
Duration of exposure:
1 - 8 h
Concentrations:
1-hour exposure: 0, 50, 200 and 400 ppm
4-hour exposure: 0, 20, 50 and 100 ppm
8-hour exposure: 0, 10, 20 and 50 ppm
No. of animals per sex per dose:
10 animals (5 male, 5 female)
Control animals:
yes
Details on study design:
The test substance was administered as a vapour by whole-body inhalation exposure for 1, 4 and 8 hours. For each time period 3 different test exposures (1 per test group) and a control group (receiving filtered air without test substance) were employed. Each group consisted of 5 females and 5 males. Clinical observations were performed daily (abnormalities recorded) and body weights were recorded prior to exposure and also on days 1, 6, 13 post exposure. Any animal found dead before the scheduled kill was necropsied and histopathological examined carried out on selected tissues. After a 14-day non-exposure (recovery period) all surviving rats were killed and underwent necropsy.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
other: NOAEL for lethality or irreversible effect
Effect level:
400 ppm
Exp. duration:
1 h
Sex:
male/female
Dose descriptor:
other: NOAEL for lethality or irreversible effect
Effect level:
100 ppm
Exp. duration:
4 h
Sex:
male
Dose descriptor:
other: NOAEL for lethality or irreversible effect
Effect level:
20 ppm
Exp. duration:
8 h
Sex:
female
Dose descriptor:
other: NOAEL for lethality or irreversible effect
Effect level:
50 ppm
Exp. duration:
8 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 400 ppm
Based on:
test mat.
Exp. duration:
1 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 100 ppm
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 50 ppm
Based on:
test mat.
Exp. duration:
8 h
Mortality:
1-hour exposure groups: no test-related cases of mortality
4-hour exposure groups: no test-related cases of mortality
8-hour exposure groups: 1 male death occurred at 50ppm.
Clinical signs:
other: 1-hour exposure groups: gasping, reddened ears, forelimbs and/or hindlimbs, red or clear material around the mouth and on ventral abdominal or urogenital surfaces. 4-hour exposure groups: gasping, reddened ears, forelimbs and/or hindlimbs, red or clear m
Body weight:
1-hour exposure groups: no significant changes in body weight.
4-hour exposure groups: no significant changes in body weight.
8-hour exposure groups: transient body weight loss in the 50ppm group.
Gross pathology:
1-hour exposure groups: no significant test-related changes compared to control.
4-hour exposure groups: no significant test-related changes compared to control.
8-hour exposure groups: no significant test-related changes compared to control.
Other findings:
Microscopic examination:
- 1-hour exposure groups: reversible nasal cavity changes. Degeneration of the olfactory epithelium, metaplasia of olfactory epithelium, chronic inflammation and haemorrhage.
- 4-hour exposure groups: reversible nasal cavity changes. Degeneration of respiratory epithelium, degeneration of olfactory epithelium, chronic inflammation and goblet cell hyperplasia.
- 8-hour exposure groups: reversible nasal cavity changes (degeneration, erosion, degeneration and erosion of the respiratory epithelium, chronic inflammation, haemorrhage and hyperplasia of goblet cells) plus in 2 males irreversible changes (ulceration, respiratory metaplasia, severe degeneration of olfactory epithelium).

Any other information on results incl. tables

Novel stimulus/arousal response:

1 -hour exposure groups: no significant effects

4 -hour exposure group: weak sedating effect at 50ppm and 100ppm

8 -hour exposure group: weak sedating effect at 20ppm and 50ppm

Haematology:

1 -hour exposure groups: no significant differences in haematology and coagulation parameters compared to the control group.

4 -hour exposure groups: no significant differences in haematology and coagulation parameters compared to the control group.

8 -hour exposure groups: no significant differences in haematology and coagulation parameters compared to the control group.

Applicant's summary and conclusion

Conclusions:
Reversible nasal cavity changes indicative of primary irritation were observed in rats of all test groups. Irreversible nasal cavity changes were seen in 2 males exposed at 50 ppm for 8h (1 male dying after this exposure). NOAEL values for lethality or irreversible effects are shown below.
 
1 -hour NOAEL = 400 ppm
4 -hour NOAEL = 100 ppm
8 -hour NOAEL = 20 ppm (males, 50 ppm (females)
Executive summary:

NOAEL values for lethality or irreversible effects in this study were: 

1 -hour exposure, 400 ppm

4 -hour exposure, 100 ppm

8 -hour exposure, 20 ppm (males), 50 ppm (females)