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Description of key information

Valid data could be identified for assessment of the skin and eye irritating potential of valeraldehyde.
In a primary dermal irritation study, valeraldehyde proved to be a dermal irritant (BASF AG, 1999).
In a primary eye irritation study, valeraldehyde demonstrated to be irritating to the eye (BASF AG, 1977).
In a sensory irritation experiment, a RD50 of 1120 ppm was determined during inhalation exposure of mice to valeraldehyde (Steinhagen, 1984) indicating the potential of respiratory irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

 

Skin irritation data for valeraldehyde are reported by BASF (1999) and by Smyth (1969 and 1962).

 

The BASF study on skin irritation is a GLP study according to OECD test guideline 404 with a reliability of 1. It is selected as key study.

 

The methods and evaluation/scoring systems used in the studies of Smyth are different from actual test guidelines with profound deviations and results are not comparable to data obtained according to recent test guidelines. Furthermore, in the study from 1962, the test substance (1-pentanal) is indicated as "mixed isomers" causing doubts on the nature of the test material as single substance. For both studies, reliability is 3.

 

BASF AG 1999

 

In a primary dermal irritation study according to OECD test guideline 404 (Acute Dermal Irritation/Corrosion), three young adult male New Zealand White rabbits were dermally exposed to 0.5 mL of valeraldehyde (purity 98.5%) for 4 hours applied to a 2.5 x 2.5 cm body surface area. Animals then were observed for 14 days. Irritation was scored according to the grading system of OECD test guideline 404 (method of Draize).

 

Erythema was noted starting from 1 h after removal of the patch (all 3 animals) up to 14 days (1 animal) with maximum scores of 3. Edema was less pronounced (only 2 animals, shorter period, maximum score of 2). Mean erythema and edema scores (24. 48, and 72 h, all animals) were 1.78 and 0.44 respectively. In this study, valeraldehyde was demonstrated to be a dermal irritant (BASF AG, 1999).

 

Eye irritation

 

Eye irritation data for valeraldehyde are reported by BASF (1977) and by Smyth (1969 and 1962).

 

The BASF study on eye irritation bears some deviations from recent guidelines (only 2 animals tested, dose applied only 0.05 mL, no grading of eye reaction at 72 h). Nevertheless, the data are assessed to be sufficiently valid to evaluate the eye irritation potential of valeraldehyde. Using available date conforms to the testing and evaluation strategy for eye irritation/corrosion and helps avoid further testing. This study is selected as key study.

 

The methods and evaluation/scoring systems used in the studies of Smyth are different from actual test guidelines with profound deviations and results are not comparable to data obtained according to recent test guidelines. Furthermore, in the study from 1962, the test substance (1-pentanal) is indicated as "mixed isomers" causing doubts on the nature of the test material as single substance. For both studies, reliability is 3.

 

BASF AG 1977

 

In an acute eye irritation/corrosion test, 2 rabbits were exposed to 0.05 mL valeraldehyde each. Irritation reactions of cornea and conjunctivae developed within 1 hour after application and persisted up to a maximum of 8 days. At the end of the observation period (8 days) all irritation effects had subsided.

 

For rabbit 1, the mean (24 and 48 h, no reading at 72 h) cornea and conjunctivae score were 0.5 and 1.5 respectively. For rabbit 2, the mean cornea and conjunctivae score were 1.5 and 2 thus exceeded or reaching the EU criteria for classification (reversible effect on the eye - Category 2) (BASF AG, 1977). Considering the dose applied and the time course of the development of irritating effects, valeraldehyde requires classification as irritating to eyes (Category 2).

 

Respiratory irritation

 

In a sensory irritation experiment conducted following accepted scientific principles, B6C3F1 mice and Swiss-Webster mice were exposed head only in groups of 4 to graduate concentrations of valeraldehyde vapor. Respiratory rates were recorded by means of a body plethysmograph. The average maximum decrease in respiratory rate for 1 min was computed from the response of each group of animals. The RD50 value was calculated from the resulting concentration-response curve.

 

RD50 values of 1190 ppm and 1121 ppm were determined for B6C3F1 and Swiss-Webster mice, respectively demonstrating that valeraldehyde is respiratory irritating (Steinhagen, 1988).

 

(The endpoint study record for this study is located in IUCLID Section 7.9.3 - Specific investigations: other).


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Skin irritation

 

Mean erythema score for gradings at 24, 48, and 72 h was 2 and higher for 2 animals out of 3. Thus according to Directive 67/548/EEC, classification as irritating to skin is required for valeraldehyde (R38: Irritating to skin).

 

However, classification criteria of Regulation (EC) No 1272/2008 are not met. The cut off value of 2.3 for mean erythema or edema scores from gradings at 24, 48, and 72 h was exceeded in only one test animal but not in 2 as required. Similarly, inflammation persisted only in 1 animal until the end of the observation period (14 d) but not in 2. Thus, no classification regarding skin irritation under Regulation 1272/2008 is required.

 

Eye Irritation

 

The eye irritation study of BASF (1977) includes some deviations from test guidelines (amount of test substance only 0.05 mL, only 2 animals tested, grading only at 24 and 48 h, but not at 72 h).

 

The scores taken were moderate (mean of 24 and 48 h gradings 0.5 to 2). The effects observed were totally reversible within 8 days. This data would indicate classification as irritating to eyes (Category 2) according to Regulation (EC) No 1272/2008 but no classification according to Directive 67/548/EEC.

 

As consequence of using the required amount of test substance in this eye irritation test, more pronounce effect with higher scores would have been observed. Considering the scale of effects and the time course reported, it is estimated that scores would increase but the effects would still be reversible within the observation period (14 days or 21 days).

 

In order to avoid further testing and additional use of test animals, classification will be based on the test results available under application of the above considerations.

 

Valeraldehyde will be classified as irritating to the eye based on both, Directive 67/548/EEC (R 36: Irritating to eyes) and Regulation (EC) No 1272/2008 (irritating to eyes - Category 2).