Valeraldehyde

Endpoint summary

Description of key information

The oral LD50 of valeraldehyde was determined to be 6490 mg/kg bw in male rats (BASF, 1977).
The inhalation LC50 of valeraldehyde was determined to be 14.3 mg/L in rats (Smyth, 1969).
The dermal LD50 of valeraldehyde was determined to be 4857 mg/kg in male rabbits (Smyth, 1969).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

An internal BASF method was used which was in large part equivalent to OECD guideline 401

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: mean 170 g (male), 150 g (female)
- Diet (e.g. ad libitum): ad libitum, Altronin R 1121
- Water (e.g. ad libitum): tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: 0.5% CMC with Cremophor EL

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 46.4, 50%
- Amount of vehicle (if gavage): 20 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 3.4 mL

Doses:

4640, 6810, 10000 µL/kg bw (approx. 3763, 5522, 8109 mg/kg bw based on a density of 0.8109 g/mL)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and weighing prior to study and days 2, 7 and 13
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 6 490 mg/kg bw

Remarks on result:

other: LD 50 converted from the orignally reported value of 8 mL/kg bw (based on a density of 0.8109 g/ml)

Mortality:

4640 µl/kg bw (3763 mg/kg bw): no mortality
6810 µl/kg bw (5522 mg/kg bw): 2/5 males within 24 h; 1/5 females within 24 h
10000 µl/kg bw (8109 mg/kg bw): 4/5 males within 24 h; 4/5 females within 24 h

Clinical signs:

other: dyspnoea, apathy, face-down, lateral and dorsal position, staggering, atony, narcosis-like state with loss of pain- and corneal reflex, spastic move, exsiccosis, exophtalmus, reduced general state

Gross pathology:

heart: acute bilateral dilatation, congestive hyperemia
stomach: gastroesophageal vestibule septum thickened and sclerotic, agglutination, cauterisation gastritis

Mean weights:

dose (µl/kg bw)	sex	mean weight (g)
		prior to study	d 2	d 7	d 13
10000	m	170	176	194	223
	f	150	156	176	188
6810	m	170	181	252	252
	f	150	152	190	190
4640	m	170	194	225	242
	f	150	171	183	194

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of valeraldehyde was determined to be 6490 mg/kg bw. No classification is required according to EU CLP (1272/2008/EC) not met.

Executive summary:

The acute oral toxicity of valeraldehyde was determined in groups of 5 male and 5 female Sprague-Dawley rats receiving the test material by oral gavage at doses of 3760, 5520, 8110 mg/kg bw. The observation period was 14 days. The LD50 was estimated using a graphical evaluation of the dose response curve on probability paper. Overall, the study was conducted in accordance with the recently retracted OECD test guideline 401.

 

The acute oral LD50 was determined to be 6490 mg/kg bw in rats (BASF, 1977).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

6 490 mg/kg bw

Quality of whole database:

Sufficient for classification

Acute toxicity: via inhalation route

Link to relevant study records

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

14 300 mg/m³ air

Quality of whole database:

Sufficient for classification

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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 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

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

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.

Sex:

male

Dose descriptor:

LD50

Effect level:

4 857 mg/kg bw

Remarks on result:

other: LD50 is originally reported in mL/kg bw

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.

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.

Endpoint conclusion

Dose descriptor:

LD50

Value:

4 857 mg/kg bw

Quality of whole database:

Sufficient for classification

Additional information

Acute toxicity: oral

 

For the assessment of the acute oral toxicity of valeraldehyde, two valid studies are available (Smyth 1969, BASF 1977; both RL 2). In the study of Smyth, the highest dose tested did not cause any lethality (LD0 = 4582 mg/kg bw). In the BASF study, a LD50 could be determined (LD50 = 6490 mg/kg bw; highest dose tested 8109 mg/kg bw, mortality 8/10 animals). Thus the BASF study is taken as key study with its LD50 of 6490 mg/kg bw.

In the older study of Smyth (1962), the LD50 was determined to be 3850 mg/kg bw. However, the test substance (1-pentanal) is indicated as "mixed isomer" causing doubts on the nature of the test material as a single substance. Thus, the reliability is rated to be 3 and the LD50 is disregarded.

 

BASF 1977

 

The acute oral toxicity of valeraldehyde was determined in groups of 5 male and 5 female Sprague-Dawley rats receiving the test material by oral gavage at doses of 3760, 5520, 8110 mg/kg bw. The observation period was 14 days. The LD50 was estimated using a graphical evaluation of the dose response curve on probability paper. Overall, the study was conducted in accordance with the recently retracted OECD test guideline 401.

 

The acute oral LD50 was determined to be 6490 mg/kg bw in rats (BASF, 1977).

 

Smyth (1969)

 

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

 

Acute toxicity: inhalation

 

To assess the acute inhalation toxicity potential of valeraldehyde, only one valid study is available (Smyth, 1969). In the older study of Smyth (1962), the test substance (1-pentanal) is indicated as "mixed isomer" causing doubts on the nature of the test material as single substance (RL 3). In the study of Salem (1969), only one test concentration was used and exposure time was 10 h given that the test animals survived this time (RL 3).

 

Smyth (1969)

 

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 (ca. 90 mg/L at 20°C).

 

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).

 

Acute toxicity: dermal

 

For assessment of the acute dermal toxicity of valeraldehyde, only one valid study is available (Smyth, 1969). In the older study of Smyth (1962), the test substance (1-pentanal) is indicated as "mixed isomer" causing doubts on the nature of the test material as single substance (RL 3).

 

Smyth (1969)

 

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).

Justification for classification or non-classification

Acute oral toxicity

 

The LD50 of the key study (BASF, 1977) was 6490 mg/kg bw in rats. This exceeds the limit values for classification (2000 mg/kg bw) according to Regulation (EC) No 1272/2008. Classification based on EU regulations is not required.

 

Acute inhalation toxicity

 

The LC50 of valeraldehyde for a 4 h exposure period was determined to be 14.3 mg/L. This value falls in the range of 10.0 to 20.0 mg/L (vapours) according to Regulation (EC) No 1272/2008) requiring classification as Category 4.

 

Acute dermal toxicity

 

The LD50 value in rabbits was determined to be 4857 mg/kg bw (Smyth, 1969). This exceeds the cut off value of 2000 mg/kg bw for classification according to Regulation (EC) No 1272/2008. Classification based on EU regulations is not required.