Valeraldehyde

Acute Toxicity: oral

Administrative data

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

deviations from test guideline: only 2 animals tested, dose applicated 0.05 mL, no grading of eye reaction at 72 h

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

An internal BASF method was used (deviations from OECD test guideline: only 2 animals tested, dose applicated 0.05 mL, no grading of eye reaction at 72 h)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 2.78, 3.06 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: NaCl-treated eye of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 ml
- Concentration (if solution): 100%

Duration of treatment / exposure:

one application

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
The original BASF grading was converted into the numerical grading according to the OECD Draize system:
Cornea
(A) Opacity-degree of density (area most dense taken for reading)
0 = No opacity
1 = Scattered or diffuse area, details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Opalescent areas, no details of iris visible, size of pupil barely discernible
4 = Opaque, iris invisible

(B) Area of cornea involved
1 = One quarter (or less) but not zero
2 = Greater than one quarter, but less than half
3 = Greater than half, but less than three quarters
4 = Greater than three quarters, up to whole area

Iris
(A) Values
0 = Normal
1 = Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination af any thereof) iris still reacting to light (sluggish reactions is positive)
2 = No reaction to light, hemorrhage, gross destruction (any or all of these)

(3) Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
0 = Vessels normal
1 = Vessels definitely injected above normal
2 = More diffuse, deeper crimson red, individual vessels not easily discernible
3 = Diffuse beefy red

(B) Chemosis
0 = No swelling
1 = Any swelling above normal (includes nictitatinq membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids about half closed to completely closed

(C) Discharge
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye



TOOL USED TO ASSESS SCORE: fluorescein at day 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 48h

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 8 d

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48 h

Score:

1.5

Max. score:

3

Reversibility:

fully reversible within: 5 d

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7

Remarks on result:

probability of weak irritation

Readings	Animal	Corneal opacity	Iris	conjunctiva
				Erythema	Chemosis	Additional findings
1h	1	1	0	1	2
	2	1	0	1	2	o
3 h	1	1	0	1	2	o
	2	1	0	1	2	o
24 h	1	1	0	2	1	o, s
	2	1	0	2	1	o
48 h	1	0	0	1	1	o, s
	2	2	0	2	1	o
5 d	1	0	0	0	0
	2	1	0	1	0	o
7 d	1	0	0	0	0
	2	1	0	0	0
8 d	1	0	0	0	0
	2	0	0	0	0
Mean 24 - 48 h	1	0.5	0.0	1.5	1.0
	2	1.5	0.0	2.0	1.0
Mean		1.0	0.0	1.8	1.0

o: smudgy overlay

s: scar

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

After application of 0.05 mL of test substance to 2 rabbit eyes, mean (24 and 48 h, no reading at 72 h) cornea scores of 0.5 and 1.5 and conjunctivae scores of 1.5 and 2 were observed for the two test animals respectively. All effects were fully reversible within 8 d at the maximum. For one rabbit, classification criteria of regulation (EC) No 1272/2008 for reversible effects on the eye (Category 2) are reached or exceeded. Considering the time course of cornea scores for rabbit 2, mean cornea score will be > 1 even if a 72 h reading were available. In addition, the amount of the dose applied (0.05 mL instead of 0.1 mL according to EU test guideline) has to be allowed for. It is estimated that with the higher dose, the reversibility of effects still will be maintained but the scores will be elevated. Thus, valeraldehyde is assessed to be irritating to the eye (Category 2) according to EU regulations.

Executive summary:

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 scores were 0.5 and 1.5 respectively. For rabbit 2, the mean cornea and conjunctivae scores were 1.5 and 2 thus exceeded or reaching the EU criteria for classification (reversible effect on the eye - Category 2) (BASF 1977). Considering the dose applied and the time course of the development of irritating effects, valeraldehyde requires classification as irritating to eyes (Category 2).

 

For recent primary eye irritation tests in vivo, test guidelines require the application of 0.1 mL test substance. Considering the data available and the time course of the eye irritating effects, it is estimated that with the higher dose, scores will be elevated but still remain below the criteria for irreversible effects and the reversibility of effects within 21 days will be maintained. Based on the data available, valeraldehyde will be classified as irritating to eyes (Category 2).

 

This study bears some deviations from actual test guidelines. Nevertheless, the data are assessed to be sufficiently valid to evaluate the eye irritation potential of valeraldehyde. Using available results conforms to the tiered testing and evaluation strategy for eye irritation/corrosion and further testing can be avoided.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

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): n-Valeraldehyd
- Substance No.: XXVI 30

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).