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EC number: 203-470-7 | CAS number: 107-18-6
Toxicological information
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Peer reviewed publication of a study conducted following a method similar to OECD guideline 413. Study predates GLP.
Data source
Reference
- Reference Type:
- publication
- Title:
- The toxicity of allyl alcohol.
- Author:
- Dunlap, M.K., Kodama, J.K., wellington, J.S., Anderson, H.H., Hine, C.H.
- Year:
- 1 958
- Bibliographic source:
- AMA Archives of Industrial Health. 18:303-311
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- no
- Limit test:
- no
Test material
- 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:
- Allyl alcohol was 98.5% pure and was provided by the Shell Chemical Company. (Impurities are diallyl ether and water).
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Long-Evans
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: Rats were housed in groups of two.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: No data
- Details on inhalation exposure:
- Rats were exposed to the test substance allyl alcohol in 200 litre capacity steel chambers and the desired concentrations of vapour produced with a constant metering device. The air flow was set at 10.9 to 21.1 litres per minute (three to six changes per hour). The temperature of the exposed room was maintained at 20 to 25 C.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Atmospheric samples drawn into water, reacted with bromine in acetic acid and titrated (analyses conducted by the Analytical Chemistry department, Shell Development company, Emeryville, Calif.) See table 2 in remarks on results section for the results of the analysis).
- Duration of treatment / exposure:
- 12 weeks.
- Frequency of treatment:
- 7 hours a day, for 5 days a week, for 12 weeks (but exposures limited by mortality to 10 at 150 ppm, 55 at 100 ppm)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1, 2, 5, 20, 40, 60, 100, 150 ppm
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10 male rats/ dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Three experiments were conducted. Control groups were exposed to uncontaminated air (without test substance). The initial experiment, doses of 1, 2, 5 and 20 ppm did not produce any signs of gross toxicity and so a second experiment using doses of 40 and 60 ppm were used. A third experiment was conducted (using doses of 100 and 150 ppm).
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- See details on results below
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- See details on results below
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- See details on results below
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- See details on results below
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See details on results below
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- See details on results below
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- Mortality: Four rats from the 150 ppm group died during the first exposure, a further 2 died the following morning and 2 died during the second exposure. The remaining 2 rats from the 150 ppm group died by the 10th exposure (end of the second week). There were 6 deaths in animals exposed to 100 ppm after 46 days and 1 death following 4 days exposure to 60 ppm allyl alcohol.
-Clinical signs: Clinical signs in the 150 ppm group included gasping, severe depression, nasal discharge, eye irritation and corneal opacity. Less intense clinical signs were present in animals exposed to 40-100 ppm. Clinical signs were absent in animals exposed to 20 ppm and below.
BODY WEIGHT AND WEIGHT GAIN
Mean percentage body weight gain was statistically significantly lower in animals exposed to 20 ppm (see table 1).
ORGAN WEIGHTS
Relative kidney weights increased by 8-10% in animals exposed to 40 ppm or 60 ppm allyl alcohol vapour for 12 weeks. Relative lung weight was increased after exposure to 40 ppm allyl alcohol vapour for 12 weeks. Relative liver weights for treated animals were indistinguishable from those of the controls. (see table 1).
GROSS PATHOLOGY
Livers from rats in the 150 ppm allyl alcohol group appeared haemorrhagic and lungs were pale and spotted. The kidneys appeared normal.
HISTOPATHOLOGY: NON-NEOPLASTIC
At the 150 ppm dose group microscopic examination revealed slight congestion of the lungs and liver. At the 100, 60 and 40 ppm groups, lesions and microscopic finding were similar to that of the 150 ppm dose group but less intense.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 20 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Limited reduction of bodyweight gain seen at this level: statistically significant but of uncertain biological significance
- Dose descriptor:
- LOAEL
- Effect level:
- 40 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Increased lung weight is combined with clear retardation of weight gain at this level
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1. Mean bodyweight gains and organ/body weight ratios.
| Organ / Body weight ratios, % | ||||||
| Group | PPM | Mean % weight gain | Liver | Kidney | Lung | Mortality ratio |
| 1 | 0 | 134 +/-29 | 3.74 +/-0.25 | 0.724 +/-0.06 | - | 0/10 |
| 1 | 133 +/-5.6 | 3.61 +/-0.2 | 0.706 +/-0.04 | - | 0/10 | |
| 5 | 126 +/-17 | 3.52 +/-0.3 | 0.765 +/-0.06 | - | 0/10 | |
| 20 | 110 +/-23* | 3.61 +/-0.3 | 0.715 +/-0.08 | - | 0/10 | |
| 2 | 0 | 128 +/-43 | 3.26 +/-0.3 | 0.582 +/-0.05 | 0.410 +/-0.1 | 0/10 |
| 40 | 90 +/-24* | 3.19 +/-0.4 | 0.629 +/-0.03 | 0.435 +/-0.2* | 0/10 | |
| 60 | 75 +/-32* | 3.08 +/-0.2 | 0.043 +/-0.04* | 0.531 +/-0.2 | 1/10 | |
| 3 | 0 | 135 +/-8 | - | - | - | 0/10 |
| 100 | 75 +/-4* | - | - | - | 6/10 | |
| 150 | - | - | - | - | 10/10 | |
Table 2. Vapour analyses (higher test concentrations).
| Nominal concentration | Number of readings | Mean value | Standard deviation |
| 40 | 24 | 40.7 | 3.24 |
| 60 | 24 | 61.1 | 2.37 |
| 100 | 22 | 103.2 | 8.68 |
| 150 | 14 | 166.7 | 17.66 |
Applicant's summary and conclusion
- Conclusions:
- In this study the NOAEL and LOAEL for repeated dose toxicity via the inhalatory route in rats were 20 ppm (47.5 mg/m3) and 40 ppm (95.1 mg/m3) respectively.
- Executive summary:
In a subchronic inhalation toxicity study allyl alcohol was administered to 10 male rats (Long-Evans strain) per concentration group, by whole body exposure, at concentrations of 0, 1, 5, 20, 40, 60, 100 and 150 ppm for 7 hours per day, 5 days/week over 12 weeks. Treatment-related clinical signs were observed, beginning at 40 ppm, with treatment-related mortality observed at 60 ppm or higher.
The LOAEL was 40ppm, based on increased lung weight and clear retardation of weight gain. The NOAEL is 20 ppm .
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