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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
only 4 animals per group, occlusive wrapping, limited reporting
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
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: Comparable to guideline study with acceptable restrictions (LC50 not statistically determined, no concentrations and particle size distribution measured, only 6 rats used, sex not specified, reporting not according to test guideline)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
LC50 not statistically derived, no actual concentrations and particle size distribution measured, only 6 rats used, sex not specified, reporting not according to test guideline
Principles of method if other than guideline:
Pre-guideline study, but method is similar to OECD TG 403. A test with graduate doses (standard test) and an inhalation hazard test were performed.
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: own breeding facility
- Age at study initiation: 4 to 5 weeks
- Weight at study initiation: 90 to 120 g
- Fasting period before study: no
- Housing: no data
- Diet (e.g. ad libitum): Rockland rat diet, complete, ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Test with graduate doses (standard test)
Test atmosphere was generated by injecting definite amounts of test substance into the flowing stream of breathing air using a suitable proportioning pump.
Inhalation hazard test
Test atmosphere was generated by passing a stream of dried air at 2.5 L/min at room temperature through a fritted glass disc immersed to a depth of at least 1 inch in approximately 50 mL of the test substance contained in a gas washing bottle. Six male or female albino rats were exposed for different exposure times to this atmosphere (flowing stream of air saturated or close to saturation with vapour).
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Remarks on duration:
test with graduate doses
Concentrations:
For the standard test, doses were spaced in a logarithmic series with a factor of 2. Number of doses and individual concentrations are not reported.
For the inhalation hazard test, the test atmosphere was saturated or close to saturation with test substance vapor as indicated by the generation method of test atmosphere (saturated vapor concentration of valeraldehyde: 92 mg/L at 20°C according to Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988)
No. of animals per sex per dose:
six male or female animals per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Sex:
not specified
Dose descriptor:
LC50
Effect level:
14.3 mg/L air (nominal)
Exp. duration:
4 h
Remarks on result:
other: Standard test: at the given dose, 3 of 6 animals died. Dose is converted from ppm as reported by the authors (4000 ppm)
Sex:
not specified
Dose descriptor:
discriminating conc.
Effect level:
ca. 92 mg/L air (nominal)
Exp. duration:
15 min
Remarks on result:
other: Inhalation Hazard Test: as discriminating dose the saturated vapor concentration of test substance is given. Exposure duration is the longest exposurte time resulting in no death
Mortality:
After exposure for 4 hours to a concentration of 4000 ppm test substance (ca. 14.3 mg/L; conversion factor from ppm to µg/L = 3.58, Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988), 3 of 6 animals died within 14 days. This concentration is taken as LC50.
For the exposure to (nearly) saturated vapor, the exposure time was restricted to 15 min in order to produce no mortality.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Exposure to valeraldehyde vapor in air at a concentration of 14.3 mg/L (4000 ppm) for 4 hours resulted in the death of 3 out of 6 animals (observation period 14 days). This value indicates LC50 and corresponds to category 4 for acute inhalation toxicity according to EU regulations (Regulation (EC) 1272/2008).
Executive summary:

For this acute inhalation toxicity study, a standard graduate dose test and an inhalation hazard test were performed. The observation period for both tests was 14 days.

 

Groups of six albino rats were exposed for 4 hours to graduate doses of valeraldehyde vapor in the breathing atmosphere of test animals. Doses were spaced in a logarithmic series with a factor of 2. Actual concentrations were not measured and individual doses are not reported.

 

In the inhalation hazard test, test animals were exposed for various time periods starting from one forth hour up to 8 hours (if appropriate, spacing factor of 2) to an atmosphere saturated or close to saturation with vapor of valeraldehyde. Actual atmosphere concentrations were not measured but can be estimated to be saturated or close to saturation by the method the atmosphere was generated. Saturated vapor concentration of valeraldehyde at 20°C in air is 92 mg/L (Auer Technikum, Edition 12, Auergesellschaft GmbH, Berlin, 1988).

 

In the standard test, a concentration of 4000 ppm (ca. 14.3 mg/L) caused a mortality of 3 of 6 animals. This concentration represents the LC50.

 

In the inhalation hazard test (saturated vapor), the exposure time was restricted to 15 min in order to produce no mortality.

 

A LC50 value using a statistical method was not determined. But the concentration causing 3 deaths out of 6 animals is considered to represent the LC50. Thus the concentration of 14.3 mg/L (4000 ppm) is taken as LC50 value (Smyth 1969).

 

Standards of the OECD test guideline 403 (Acute Inhalation Toxicity) are only met with restrictions by this investigation (only 6 rats used, sex not specified, no concentrations measured, deficiencies in reporting). Due to the high volatitiy of the test substance, the nominal concentrations are estimated to be close to the actual concentrations.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
limited reporting on test substance and test performance
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
non fasted animals, limited reporting
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: own breeding
- Age at study initiation: 4 to 5 weeks
- Weight at study initiation: 990 to 120 g
- Fasting period before study: no
- Housing: no data
- Diet (e.g. ad libitum): Rockland rat diet, complete

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Whenever possible, the test substance was administered undiluted.
Doses:
Doses were arranged in a logarithnic series differing by a factor of two.
No data on individual doses.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Statistics:
LD50 values were calculated by the method of Thompson (Thompson WR 1947, Bacteriol Rev 11, 115) using the Tables of Weil (Weil GS 1952, Biometrics 8, 249). The figures in parentheses show the limits of +/- 1.96 standard deviations.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 582 mg/kg bw
Remarks on result:
other: Highest dose tested; no fractional mortality was observed with the various doses tested; no limits of standard deviation could be calculated.
Mortality:
None of the doses tested resulted in fractional mortality. No mortality was observed even at the highest dose tested.

The highest tested dose is reported as 5.66 mL/kg bw. Using a density of 0.8095 g/mL (Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988), this value is converted to 4582 mg/kg bw.

Interpretation of results:
other: GHS critertia under EU CLP (1272/2008/EC) not met
Conclusions:
The acute oral LD50 of valeraldehyde is > 4582 mg/kg bw (highest dose tested, no mortality). No classification is required according to EU CLP (1272/2008/EC).
Executive summary:

The acute oral toxicity of valeraldehyde was determined in groups of 5 male Carworth-Wistar rats receiving the test material by oral gavage. The doses were spaced by a factor of 2 (logarithmically). The observation period was 14 days. The LD50 was calculated according to the method of Thomson (1947). No fractional mortality was observed for valeraldehyde at the various doses tested. Thus there was no mortality at the highest dose tested. No limits of standard deviations could be calculated. Overall the study was conducted in accordance with the recently retracted OECD test guideline 401.

 

The acute oral LD50 was determined to be > 4582 mg/kg bw in rats (Smyth et al., 1969) (LD0 = 4582 mg/kg bw).

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
test substance application (amount, concentration) and evaluation (scoring) of eye reactions not according to OECD test guideline 405 or Draize.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Pre-guideline study; primary eye irritation test, but quantity of test substance applied and scoring system (reference 2: Carpenter, 1946) are study specific and different from OECD TG 405 or Draize.
GLP compliance:
no
Remarks:
pre-GLP study
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye of the animal
Amount / concentration applied:
0.005 and 0.02 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
24 h
Number of animals or in vitro replicates:
5
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: specific proprietary scoring system different from the system of Draize or OECD TG 405

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: visual examination in strong diffuse daylight and after staining with fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
5
Max. score:
10
Reversibility:
not specified
Remarks on result:
other: distinct grading system different from grading scores of OECD TG 405 or Draize

Application of 0.005 mL of pure test substance for 24 hours caused an injury grade 5 (severe eye injury) of a scale with a maximum score of 10. The specific character and severity of the eye injury cannot be extracted from the score.

Interpretation of results:
study cannot be used for classification
Conclusions:
The test result indicate that the test substance causes severe eye injury. Due to methodological deficiencies, this study cannot be used for classification.
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
test substance volume only 0.01 ml; evaluation of skin reactions not according to OECD test guideline 404 or Draize, application site: belly
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Primary skin irritation test, but only 0.01 mL of test substance is applied, specific grading system different from OECD TG 404 or Draize.
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals or test system and environmental conditions:
no data
Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.01 mL
Duration of treatment / exposure:
24 h
Observation period:
no data
Number of animals:
5
Details on study design:
TEST SITE
- Area of exposure: rabbit belly
- % coverage: no data
- Type of wrap if used: application site uncovered

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

SCORING SYSTEM: own scoring sytem ranging from grade 1 (no reaction from undiluted sample) to grade 10 (edema as maximum reaction from diluted (aceton) sample, concentration < 0.01%)
Irritation parameter:
overall irritation score
Time point:
other: 24 h
Score:
2
Max. score:
10
Remarks on result:
other: distinct grading system, score 2 indicates weak reaction (least visible capillary injection)

Primary irritation was recorded in a 10-grade ordinal series of a dose-related reaction: Here the reaction score is 2, indicating a week irritation reaction (least visible capillary injection).

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the conditions of this primary irrtiation test (0.01 mL of test substance administered), valeraldehyde was found to be only very weakly irritating to rabbit skin (barely perceptible capillary injection). However, due to methodological deficiencies this study cannot be used for classification according to Regulation (EC) 1272/2008.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1969
Report date:
1969

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 4 animals per group, occlusive wrapping, limited reporting
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Valeraldehyde
EC Number:
203-784-4
EC Name:
Valeraldehyde
Cas Number:
110-62-3
Molecular formula:
C5H10O
IUPAC Name:
pentanal
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): valeraldehyde
- no further information on test substance

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 - 3.5 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: part of the trunk
- % coverage: no data
- Type of wrap if used: impervious plastic film
- Restraining of animals: animals are immobilized during the 24 h exposure period

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): graduate doses were applied, but individual doses are not specified
Duration of exposure:
24 hours
Doses:
no individual doses specified
No. of animals per sex per dose:
4 male animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Statistics:
LD50 values were calculated by the method of Thompson (1947, Bacteriol. Rev. 11, 115) using the tables of Weil (1952, Biometrics 8, 249). The limits of ± 1.96 standard deviations are presented.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
4 857 mg/kg bw
Remarks on result:
other: LD50 is originally reported in mL/kg bw

Any other information on results incl. tables

The acute dermal LD50 was reported as 6 mL/kg bw. Using a density of 0.8095 g/mL (Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988), the LD50 calculates to 4857 mg/kg bw. There is no information on local effects reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 was 4857 mg/kg bw in male rabbits. No classification is required according to Regulation (EC) 1272/2008.
Executive summary:

The acute dermal toxicity of valeraldehyde was determined in groups of 4 male albino New Zealand rabbits receiving graduate single doses of test substance per group. Number and quantity of individual doses are not specified. The exposure time was 24 hours followed by an observation period of 14 days. Individual data on mortality, weight development, clinical signs and gross necropsy findings are not reported. From mortality data, the LD50 and a range of ± 1.96 SD was calculated according to the method of Thomson (1947).

 

The acute dermal LD50 for valeraldehyde was determined to be 4857 mg/kg bw in rabbits (Smyth, 1969).

 

Overall, the study was conducted similar to OECD test guideline 402 with some restrictions (only 4 animals per group, occlusive wrapping, limited reporting). The deviations from the test guideline are considered not to invalidate the result. It is rather estimated that the value determined is close-by a result from a test in compliance with the test guideline and will be located within its range of uncertainty.