Butan-1-ol

Endpoint summary

Description of key information

skin
rabbit, 2 h, occlusive: irritating (production substance; standardized BASF test; BASF 1979a)
rabbit, 24 h, occlusive: irritating (production substance; Draize test; BASF 1979b)
rabbit, 4 h, semiocclusive: not irritating (pure substance; GLP, OECD 404; Hoechst 1988)

rabbit, 24 h, occlusive: variable results from 22 laboratories (Weil 1971)

rabbit, 24 h, not occlusive: not irritating (Union Carbide Corporation 1951: administration of 0.01 mL)

eye
rabbit, 24 h, 0.1 mL: risk of serious eye damage due to irreversible effects after 7 d observation period (OECD 405, GLP; Hoechst 1988)
rabbit, 24 h, 0.1 mL: irritating due to reversible effects within 21 d (OECD 405, GLP; ECETOC 1998)
human, 10 year study on workers: No effects on human eyes in concentrations <= 310 mg/m3 (= 100 ppm; Sterner et. al. 1949)

rabbit, 8 days, 0.1 mL: irritating potential (BASF 1979; scoring according to Draize)

rabbit,24 h, 0.5 mL: severe eye injury by undiluted compound (Union Carbide Corporation 1951)

Respiratory system
Human, 3-5 min: sensory irritating effects on nose and throat (Nelson et al. 1943)
Rat, inhalation hazard test, 7 h: irritating effects on the respiratory system (BASF 1980)

human, 10 year study on workers: No signs of irritation in human at concentrations <= 310 mg/m3 (= 100 ppm; Sterner et. al. 1949)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Two rabbits were exposed to the test substance for 5 minutes, 1 hour and 2 hours under occlusive conditions. The animals were observed for 8 days.

GLP compliance:

no

Specific details on test material used for the study:

product No. 03331, 78/305

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.97 - 3.4 kg


ENVIRONMENTAL CONDITIONS
no data

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

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

Duration of treatment / exposure:

5 minutes, 1 hour and 2 hours

Observation period:

8 days

Number of animals:

two animals per exposure period

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

exposure for 2 hours

Time point:

other: 24/48/72 hours

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: superficial necrosis

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

exposure for 2 hours

Time point:

other: 24/ 48/ 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 8 d

Remarks on result:

other: superficial necrosis

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

exposure for 2 hours

Time point:

other: 24/48/ 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: edema extending beyond the area of exposure

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

exposure for 2 hours

Time point:

other: 24/ 48/ 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 d

Remarks on result:

other: extending beyond the area of exposure

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

exposure for 1 hour

Time point:

other: 24/48 hours

Score:

2.5

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: scaling

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

exposure for 1 hour

Time point:

other: 24/48 hours

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 d

Remarks on result:

other: bloody crust, superficial necrosis

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

exposure for 1 hour

Time point:

other: 24/48 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

exposure for 1 hour

Time point:

other: 24/ 48 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 d

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

exposure for 5 min

Time point:

other: 24/48/ 72 hours

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

exposure for 5 min

Time point:

other: 24/ 48/ 72 hours

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 d

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

exposure for 5 min

Time point:

other: 24/48/ 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

exposure for 5 min

Time point:

other: 24/48/ 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 d

Exposure for 2 hours under occlusive conditions led to superficial necrosis. No full thickness destruction of the skin occurred.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, own breeding facilities
- Age at study initiation: ca. 3-5 months
- Weight at study initiation: 2.7 - 3.2 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +- 3
- Humidity (%): 50 +- 20
- Air changes (per hr): fully air conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

not rinsed

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological sodium chloride solution
- Time after start of exposure: 24 hours


SCORING SYSTEM: according to OECD guideline 405


TOOL USED TO ASSESS SCORE: fluorescein (not at all readings)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

2.11

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

2.89

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Time p.a.	1 h			24 h			48 h			72 h			7 d
Animal No.	1	2	3	1	2	3	1	2	3	1	2	3	1	2	3
Conjunctival swelling	3	3	3	3	3	3	4	3	3	3	3	2	3	3	1
Conjunctival reddening	2	2	1	3	3	2	3	3	3	3	3	3	3	3	2
Iris	1	1	1	1	1	1	1	1	1	+	1	1	+	1	0
Corneal opacity	1	1	1	2	1	1	4	2	1	4	2	2	4	2	2
Eye discharge: clear, uncoloured	x	x	x
Eye discharge: white, smeary				x	x	x	x	x	x	x	x	x	x	x	x
Conjunctiva: white-coloured							x
Conjunctiva: with bleeding				x			x	x	x
Iris: reddened	x	x	x	x	x	x	x	x	x		x	x		x
Iris: due to intense clouding not readable										x			x		x
Cornea: vascularization - weak distinct															x
Cornea: vascularization - clearly distinct													x	x
Cornea: rough												x

+ could not be assesst due to severe opacity

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Various experimental data were available. Pure butan-1-ol caused only slight and reversible skin irritation. For typically produced substances, however, the effects on skin are more distinct. On rabbit eyes, results indicate a risk for serious eye damage.

 

Skin

In a standardized test, two rabbits were exposed to butan-1 -ol (purity unknown; taken directly from the production) for up to 2 h under occlusive conditions (BASF 1979a). Exposure for 2 h caused superficial necrosis, erythema and edema after 24 and 48 h. These effects were not fully reversible within 8 d. Exposure for 1 h caused erythema and edema after 24 and 48 h. These effects were also not fully reversible within 8 d. Exposure for 5 min caused slight erythema and edema which were completely reversible within 8 d.

Another test with the same test substance was performed following the harsh Draize scheme (6 rabbits treated for 24 h under occlusive conditions; BASF 1979b). Here, severe erythema and edema were observed in the 24 and 72 h reading and were not fully reversible within 8 d. No necrosis was found. Both described tests used a test substance directly taken from the production process which has to be considered as typical substance type.

Another study was performed with the pure substance and showed low irritation effects; this study was performed according to OECD TG 404 and GLP (i.e. 4 h under semiocclusive conditions; Hoechst 1988). In general, variable results were observed in an interlaboratory comparison of studies with a 24 h exposure period and occlusive conditions (Weil et al. 1971).

Skin irritation potential of n-butanol was examined by placing 0.01 mL of test material to the shaved skin of albino rabbits, while the application site was examined after 24 hours. No irritation of the rabbit skin was observed. Test material was applied at 0.01 mL, lower than current guideline which recommended 0.5 mL ( Union Carbide Corporation 1951).

              

Eye

A GLP conform study was performed with three rabbits exposed for 24 h to 0.1 mL according to OECD guideline 405 (Hoechst 1988). Corneal opacity, iritis, conjunctivae redness and chemosis were observed and were not fully reversible within 7 d, indicating a serious risk for eye damage. However, the observation period was not sufficient to detect irreversibility as the recommended observation period is 21 d.  

Comparable conditions were used in another GLP guideline study by ECETOC (1998). Here, corneal opacity, iritis, conjunctivae redness and chemosis were observed to be fully reversible within at least 21 d.

Results of further tests indicate irritant to severe irritant effects on rabbit eyes (i.e. BASF 1979). Test material (0.5 mL undiluted or 5 or 15% dilutions in propylene glycol) were applied to the cornea of albino rabbits and the eyes are reexamined after 24 hours. The rabbit eye was severely injured by the undiluted compound (0.5 ml), moderately damaged by a 15% dilution in propylene glycol and only slightly affected by a 5% dilution applied in excess (Union Carbide Corporation 1951).

 

Respiratory system

In an inhalation hazard test which was performed similar to the test system described in the Annex of the OECD 403, six Sprague-Dawley rats were exposed once to a saturated vapour atmosphere of butan-1-ol (nominal conc. ca. 21.48 mg/L) for 7 h (BASF 1980, see acute inhalation toxicity). Irritating effects on the respiratory system were observed during the 14 -d observation period. An older study was performed with volunteers to estimate the sensoratory limits of certain solvent vapours (Nelson et al. 1943). 25 ppm (=0.075 mg/L) Butan-1-ol caused signs of sensory irritation in nose and throat in the majority of the test subjects after 3 -5 min.

 Relevant data on human occupational hazard were provided by Sterner et al. (1949; see human data chapter). In a longitudinal study over 10 years, measured exposure levels of up to 99 workers were correlated with findings of clinical signs, lung X-ray and clinical chemistry. No eye injuries or symptoms were found in any individual at concentrations averaging 310 mg/m3 (= 100 ppm), while average concentrations of 620 mg/m3 (200 ppm) caused transient corneal inflammation, with associated burning sensation, lacrimation, and photophobia. No systemic effects have been observed.

 

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008. Results of studies performed with a mixture typically for the production process led to a classification as skin irritant (Cat. 2, H315: "Causes skin irritation") under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.

Due to the irreversible and severe effects on corneal opacity, iritis, conjunctivae redness and chemosis within 7 d, the substance is classified as risk for serious eye damage (Cat. 1, H318: "Causes serious eye irritation") according to 1272/2008/EC (CLP) requirements, as amended for the ninth time in Regulation (EU) No 2016/21179.

Due to the observed local irritant effects on the respiratory system in an inhalation hazard test and in humans and transient effects on the CNS (drowsiness and dizziness) the substance is classified as STOT Single Exposure Cat. 3 (H335: "May causes respiratory irritation"/H336 "May cause drowsiness or dizziness") according to 1272/2008/EC (CLP) requirements.