Butyraldehyde

Endpoint summary

Description of key information

The results of a modern, guideline-compliant dermal irritation study show that the substance is a slight skin irritant and does not require classification as a skin irritant. The results of a modern, guideline-compliant eye irritation study show that the substance requires classification as an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-07-05 to 1988-07-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study without deviations

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Toxicology, conventional breeding
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.0 - 2.7 kg bw
- Housing: single in cages, acclimatised room
- Diet (e.g. ad libitum): Altromin 2123 ad libitum
- Water (e.g. ad libitum): deionised chlorinated water from automatic drinkers ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: Not documented

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

30-60min, 24, 48 and 72 h
if necessary 7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25cm2 dorsal area of the trunk
- % coverage: Not documented
- Type of wrap if used: semi occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test site was washed with lukewarm tap water.
- Time after start of exposure: 4 after the start of exposure.

SCORING SYSTEM:

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other: Mean value

Other effects:

No further information

Results of skin irritation study
Observation time	1		2		3
	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1 h	2	0	2	0	1	0
24 h	0	0	2	0	2	1
48 h	0	0	1	0	1	0
72 h	0	0	1	0	2	0
Mean value 24 + 48 + 72 h	0.00	0.00	1.33	0.00	1.67	0.33
Reversibility	Yes	Yes	Yes	Yes	Yes	Yes

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No classification
Based on GHS, no classification required

Executive summary:

In a valid standard guideline study using 3 rabbits according to OECD 404 and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion), semiocclusive exposure of 4 h to undiluted butyraldehyde (0.5 ml) produced slight skin irritation: One through 72 hours after removal of the cover, barely perceptible (score 1) to distinct erythemas (score 2) were observed in all animals with a slight oedema in one animal after 24 h (score 1). All these effects subsided within 1 d in 1/3 animals and within 7 d in 2/3 animals, while the treated skin sites was still slightly scaly at this time.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-08-03 to 1981-08-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, national standard study, without GLP

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dutchland Laboratories, Inc., Denver, Pennsylvania.
- Age at study initiation: Young adults
- Weight at study initiation: 2.2 - 3.0 kg
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum Municipal water supply.
- Acclimation period: 21 day (equilibration period)


ENVIRONMENTAL CONDITIONS
- Temperature: 17.2 - 20.5 °C (monitored twice daily)
- Humidity (%): not specified (monitored daily)
- Air changes (per hr): not documented
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.

IN-LIFE DATES: From: July 13th 1981 To: August 17th 1981

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
The test material was administered as received.

Duration of treatment / exposure:

single dose

Observation period (in vivo):

Approximately 24, 48, and 72 hours and 4 and 7 days after treatment.
Up to 14 days if signs of irritation were evident on Day 7.
If no signs of irritation at Day 7, no additional observations were made.

Number of animals or in vitro replicates:

9

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 additional animals
- Time after start of exposure: 20 sec

SCORING SYSTEM
Draize scale according to Draize 1959 (Report Appendix A, p. 11)

Evaluation of scores:
according to 16 CFR 1500.42 (see Report, Chapter III, p. 4, and footnote Table I)

Effects such as pannus formation, blistering of the conjunctiva, ulceration were interpreted in terms of corrosivity.
"Necrosis" is obviously used in a broader sense, as it is also applied to tissue-destructive effects that are fully reversible.

TOOL USED TO ASSESS SCORE: fluorescein dye was used to confirm the presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations.

Irritation parameter:

cornea opacity score

Basis:

animal: 8292F

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.43

Irritation parameter:

iris score

Basis:

animal: 8292F

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0

Irritation parameter:

chemosis score

Basis:

animal: 8292F

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.86

Irritation parameter:

conjunctivae score

Basis:

animal: 8292F

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2

Irritation parameter:

cornea opacity score

Basis:

animal: 8293M

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.67

Irritation parameter:

iris score

Basis:

animal: 8293M

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.33

Irritation parameter:

chemosis score

Basis:

animal: 8293M

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2

Irritation parameter:

conjunctivae score

Basis:

animal: 8293M

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2

Irritation parameter:

cornea opacity score

Basis:

animal: 8290F

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0

Irritation parameter:

iris score

Basis:

animal: 8290F

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0

Irritation parameter:

chemosis score

Basis:

animal: 8290F

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.83

Irritation parameter:

conjunctivae score

Basis:

animal: 8290F

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2.33

Irritation parameter:

cornea opacity score

Basis:

animal: 8291M

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1

Irritation parameter:

iris score

Basis:

animal: 8291M

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.29

Irritation parameter:

chemosis score

Basis:

animal: 8291M

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.71

Irritation parameter:

conjunctivae score

Basis:

animal: 8291M

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2.33

Irritation parameter:

cornea opacity score

Basis:

animal: 8288F

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1

Irritation parameter:

iris score

Basis:

animal: 8288F

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.29

Irritation parameter:

chemosis score

Basis:

animal: 8288F

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.57

Irritation parameter:

conjunctivae score

Basis:

animal: 8288F

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2

Irritation parameter:

cornea opacity score

Basis:

animal: 8287M

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1

Irritation parameter:

iris score

Basis:

animal: 8287M

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 0.25

Irritation parameter:

chemosis score

Basis:

animal: 8287M

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1.625

Irritation parameter:

conjunctivae score

Basis:

animal: 8287M

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 ,11 and 14 days: 1.875

Irritation parameter:

cornea opacity score

Basis:

animal: 8286F

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.86

Irritation parameter:

iris score

Basis:

animal: 8286F

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 0.17

Irritation parameter:

chemosis score

Basis:

animal: 8286F

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 1.57

Irritation parameter:

conjunctivae score

Basis:

animal: 8286F

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7, 9 and 11 days: 2.143

Irritation parameter:

cornea opacity score

Basis:

animal: 8285M

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17

Irritation parameter:

iris score

Basis:

animal: 8285M

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17

Irritation parameter:

chemosis score

Basis:

animal: 8285M

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 1.5

Irritation parameter:

conjunctivae score

Basis:

animal: 8285M

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2.17

Irritation parameter:

cornea opacity score

Basis:

animal: 8284F

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.67

Irritation parameter:

iris score

Basis:

animal: 8284F

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 0.17

Irritation parameter:

chemosis score

Basis:

animal: 8284F

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 1.33

Irritation parameter:

conjunctivae score

Basis:

animal: 8284F

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: Mean value of 24h, 48h, 72h, 4, 7 and 9 days: 2

Irritant / corrosive response data:

In 4/6 animals, necrotic effects on the conjunctivae are stated, also in 2/3 animals whose eyes had been washed showed necrosis.
Individual effect scores were 3 for erythema in all animals at 24, 48, and 72 h, including washed eyes. Positive scores (in the sense of the Hazard Regulation 16 CFT 1500.42) were exhibited by all animals for conjunctival redness, chemosis, and necrosis as well as corneal ulceration, by 8 animals for corneal opacity, and 7 animals for iridal irritation. All animals were free of signs of ocular irritation by the end of the study (14 days).

Other effects:

Responses were slightly, but not substantially less severe in animals with washed eyes than in those with unwashed eyes.

Results of eye irritation study (24-h exposure): Mean effects scores over all animals and time (Individual data were taken from Report Table I)
	Cornea (opacity)	Iris	Conjunctiva
			Redness	Chemosis
Score (average of animals investigated)	0 to 4	0 to 2	0 to 3	0 to 4
1 h
24 h	1.67	1.00	3.00	3.00
48 h	1.75	0.42	3.00	2.33
72 h	1.50	0.67	3.00	2.17
Average 24 h, 48 h, 72 h	1.64	0.70	3.00	2.50
Reversibility*	c	c	c	c
Average time for reversion	7 d	7 d	9 d	9 d
*             c :           completely reversible                n c :        not completely reversible                n :           not reversible

Note: The average scores are not documented in the report but were calculated from the individual effects data.

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on CLP, butyraldehyde has to be allocated to the Category 2 (irritating to eyes).

Executive summary:

In a valid standard guideline study (described under 40 CFR Part 163.81 -4), undiluted butyraldehyde (0.1 ml) produced severe irritation and injury to all eye parts observed in all treated animals. The recovery period for conjunctival tissue lesions was greater than 7 d for most rabbeits. Eye washing after 20 sec after dosing failed to reduce irritating effects or responses to a significant extent. The detailed documentation of the observations and individual grading allows to evaluate the data in terms of current criteria.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-07-12 to 1988-08-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study without deviations

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Toxicoloy, conventional breeding
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.3 - 3.4 kg
- Housing: single in cages, acclimatised room

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3°C
- Humidity (%): 50 +-20
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL undiluted
unrinsed

Duration of treatment / exposure:

24 h, afterwards washing with saline and fluorescein staining

Observation period (in vivo):

1, 24, 48 and 72 h
if necessary 7 days

Number of animals or in vitro replicates:

3

Details on study design:

No additional information

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 d

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Other effects:

No additional information

Results of eye irritation study (24-h exposure): Mean effects scores over all animals and time
	Cornea	Iris	Conjunctiva
			Redness	Chemosis
Score (average of animals investigated)	0 to 4	0 to 2	0 to 3	0 to 4
1 h	0.00	0.33	2.00	2.67
24 h	0.67	0.67	2.67	2.00
48 h	1.00	0.00	2.00	1.00
72 h	1.00	0.00	1.67	0.33
Average 24 h, 48 h, 72 h	0.89	0.22	2.11	1.11
Reversibility*	c	-	c	c
Average time for reversion	7 d	-	7 d	7 d
*   c:  completely reversible

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on CLP, butyraldehyde has to be allocated to category 2 (irritating to eyes).

Executive summary:

In a valid standard guideline study using 3 rabbits according to OECD 405 and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion), instillation of a single dose of undiluted butyraldehyde (0.1 ml) produced slight to moderate irritation which completely reversed within 48 h to 7 d: One through 72 hours p.a., conjunctivae were distinctly hyperaemic (score 3 and 2), associated with slight to moderate swelling (score 3, 2, 1). In 2/3 animals, the iris was transiently reddened (score 1 and 0), and the cornea transiently diffusely turbid (scores 1 and 0). Additionally, initially a clear, later a white slimy discharge and bleeding of the conjunctivae and nictitating membranes was observed. All effects completely subsided within 7 d.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin Irritation:

In a valid standard guideline study conducted by Kreiling R and Jung R (1988) using 3 rabbits according to OECD 404 and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion), semiocclusive exposure of 4 h to undiluted butyraldehyde (0.5 ml) produced slight skin irritation: One through 72 hours after removal of the cover, barely perceptible (score 1) to distinct erythemas (score 2) were observed in all animals with a slight oedema in one animal after 24 h (score 1). All these effects subsided within 1 d in 1/3 animals and within 7 d in 2/3 animals, while the treated skin sites was still slightly scaly at this time.

 

In a study conducted by Union Carbide Corporation (1977), the test substance, butyraldehyde, was tested on 6 New Zealand White rabbits to determine its ability to induce skin irritation. The results of this study indicate that the test substance is not corrosive.

 

A study by Auletta (1981), was conducted to evaluate the primary dermal irritation produced by the test material C-243. The study was performed according to the guideline EPA 40 CFR Part 163.81 -5. The test material was applied to intact and abraded skin of 6 New Zealand White Albino rabits (3 per sex) for a period of 24 hours. The animals were observed for signs of erythema and oedema or other signs of irritation or injury 30 minutes after removal of the occlusive wrapping for a period fo 14 days. All animals exhibited necrosis at one or more sites at 24 and 72 hours. Eschar formation occurred subsequently at these sites and tissue destruction remained evident at termination of the study on day 14. Based on the results of this study, the test substance can be considered to be corrosive.

 

In the study conducted by Marhold (1972), 500 mg of butyraldehyde was applied to rabbits for a 24 hour exposure period. The application of the test substance resulted in severe skin irritation and as a result, the test substance was considered to be moderately irritating.

 

The study conducted by Kreiling R and Jung R (1988) was considered to be the key study as it satisfied the requirements of the relevant Guidelines and was considered to be reliable.

 

 

Eye Irritation:

In a valid standard guideline study conducted by Kreiling R and Jung R (1988), using 3 rabbits according to OECD 405 and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion), instillation of a single dose of undiluted butyraldehyde (0.1 ml) produced slight to moderate irritation which completely reversed within 48 hours to 7 days: One through 72 hours p.a., conjunctivae were distinctly hyperaemic (score 3 and 2), associated with slight to moderate swelling (score3, 2, 1). In 2/3 animals, the iris was transiently reddened (score 1 and 0), and the cornea transiently diffusely turbid (scores 1 and 0). Additionally, initially a clear, later a white slimy discharge and bleeding of the conjunctivae and nictitating membranes was observed. All effects completely subsided within 7 days.

 

In a valid standard guideline study conducted by Auletta (1981) (described under 40 CFR Part 163.81 -4), undiluted butyraldehyde (0.1 ml) produced severe irritation and injury to all eye parts observed in all treated animals. The recovery period for conjunctival tissue lesions was greater than 7 days for most rabbits. Eye washing after 20 sec after dosing failed to reduce irritating effects or responses to a significant extent. The detailed documentation of the observations and individual grading allows to evaluate the data in terms of current criteria.

 

In the study conducted by Union Carbide Corporation (1977), serial single instillations of diluted or undiluted test substance (Butyraldehyde) were placed in the conjunctival sac of 5 rabbits. The eyes were read immediately without fluorescein staining and then after fluorescein staining at 24 hours. The results of this study indicate severe corneal injury with iritis when applied at 0.02ml per eye. Moderate corneal injury occurred when 0.005ml test substance was applied to the eye. Based on these results and under the test conditions, the test substance can be considered to be highly irritating or corrosive.

 

In the study conducted by Smyth et al (1951), the test substance butyraldehyde was assessed for its ability to be an eye irritant. The results of this study indicate it is a Grade 8 eye irritant and as such, should be considered to be corrosive to the eye.

 

In the study conducted by Marhold (1972), the test substance, butyraldehyde, 20mg was applied to the eyes of rabbits. The rabbits were exposed to the test substance for 24 hours. Based on the results of this study, the test substance butyraldehyde was considered to be a moderate eye irritant.

 

The key studies were considered to be the study conducted by Kreiling R and Jung R (1988) and by Auletta (1981) as they were considered to be methodologically strongest and adhered to the relevant Guidelines. The remaining studies, adhered for the most part to the relevant guidelines, however, some methodological deficiencies meant their validity/reliability was questionable and as a result, they were considered to be supporting studies.

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin Irritation:

The results of the available studies are conflicting, however the majority of studies used non-standard exposure periods (24 hours) and/or abraded skin and are therefore considered to be less reliable and unsuitable as the basis for classification. The results of a modern, guideline-compliant dermal irritation study show that the substance is a slight skin irritant but does not require classification as a skin irritant according to Directive 67/548/EEC or Regulation 1272/2008/EC (CLP).

Eye Irritation:

The results of a number of eye irritation studies are consistent in demonstrating that the substance is an eye irritant, with varying degrees of irritation seen. The results of two modern, guideline-compliant eye irritation studies show that the substance requires classification as an eye irritant category 2 under Regulation 1272/2008/EC (CLP).