Butylamine

Endpoint summary

Description of key information

n-Butylamine is corrosive to skin (Category 1A) and causes sever damage to the eyes (Category 1). Further, respiratory irritation was observed after inhalation exposure.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

1 min exposure instead of 4 h, combined with various post-exposure procedures of effect mitigation

Principles of method if other than guideline:

Method: Objective was to examine three first-aid measures to prevent/mitigate corrosion

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: 2.0 - 3.5 kg
- Housing:
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21 (61 - 70 °F)
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Dose 0.5 ml

Duration of treatment / exposure:

1 minute

Observation period:

1, 24, 72 h, 7 and 14 d post-application ( 14 d added, according to Protocol Amendment No. 1 of 02 March 1993)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approx. 1 square inch
- % coverage: no data
- Type of wrap if used: gauze patch (8-ply)


REMOVAL OF TEST SUBSTANCE
Group 1 (no particular preventive measure)
Washing (if done): no, wiping with dray gauze
- Time after start of exposure: 1 min

Group 2 (rinsing)
Washing (if done): yes, 5 min distilled water (about 2 L per animal)
- Time after start of exposure: 1 min

Group 3
Washing (if done): yes, 1 min 5% (v/v) reagent-grade acetic acid/distilled water (about 0.5 L per animal)
- Time after start of exposure: 1 min

Group 4 (according to Protocol Amendment No. 1 of 02 March 1993)
Washing (if done): yes, 0.5 min distilled water (about 0.25 L per animal), 1 min PEG300 swabbing (gentle wiping) of each test site
(gauze moistend in PG300) and 3.5 min distilled water rinse (about 1.75 L per animal)
- Time after start of exposure: 1 min


SCORING SYSTEM: Draize numerical scoring system for quantitive grading of erythema and edema

Irritation parameter:

erythema score

Remarks:

(no washing, Group 1)

Basis:

animal #1

Time point:

other: 1 hour - 14 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: immediate necrosis followed by eschar formation

Irritation parameter:

erythema score

Remarks:

(no washing, Group 1)

Basis:

animal #2

Time point:

other: 1 hour - 14 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: immediate necrosis followed by eschar formation

Irritation parameter:

erythema score

Remarks:

(no washing, Group 1)

Basis:

animal #3

Time point:

other: 1 hour - 14 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: immediate necrosis followed by eschar formation

Irritation parameter:

erythema score

Remarks:

Group 1

Basis:

mean

Remarks:

mean value for animal #1, #2, and #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

Maximum score of 4 at 24 h and 72 h.

Irritation parameter:

edema score

Remarks:

no washing, Group 1

Basis:

mean

Remarks:

mean value for animal #1, #2, and #3

Time point:

24 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Remarks:

no washing, Group 1

Basis:

mean

Remarks:

mean value for animal #1, #2, and #3

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Remarks:

no washing, Group 1

Basis:

mean

Remarks:

mean value for animal #1, #2, and #3

Time point:

72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Not any of the washing measures taken could prevent the corrosive activity of n-butylamine.

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

Under the conditions of this test skin corrosive effects were already detectable after 1 min of exposure.

Executive summary:

In this dermal irritation study, 3 New Zealand White rabbits were exposed semiocclusively to 0.5 ml of the undiluted test substance on 1 square inch for 1 min. The test substance was removed by a) wiping with dray gauze; b) washing for 5 min distilled water (about 2 L per animal) or c) 1 min 5% (v/v) reagent-grade acetic acid/distilled water (about 0.5 L per animal).

Examinations of irritation/corrosion were performed 1, 24, 72 h and 7 and 14 d post-application. The effects were scored according to the Draize numerical scoring system for quantitive grading of erythema and edema. The exposure without washing produced immediate necrosis followed by eschar formation. The washing measures abated the corrosive activity of the test substance. The erythema score (without washing) was 4.0, the edema score was 2.3, and the effects were not fully reversible within 14 days. Under the conditions of this test skin the test substance was corrosive.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye 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:

BASF-Test, see details in remarks on material and methods.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Vehicle:

unchanged (no vehicle)

Controls:

other: the adjacent eye served as control treated with 0.9 % NaCl (saline).

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 50 µl

Duration of treatment / exposure:

single application

Observation period (in vivo):

5 weeks

Number of animals or in vitro replicates:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: effects not evaluable

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effects

Findings: animal1/animal2

Time	Corneal opacity	Iritis	Erythema	Chemosis
1 h	3/3	-/-	0/0	1/1
24 h	3/3	-/-	0/0	1/1
48 h	3/3	-/-	0/0	1/1
72 h	3/3	-/-	0/0	1/1
8 days	3/x	-/x	0/x	-/x

x: animal 2 was sacrificied after 5 days due to paraplegia.

-: due to corneal opacity not evaluable

The original BASF grading was converted into the numerical grading according the OECD Draize system.

Mean values over 24 h, 48 h and 72 h:.

Animal1: Opacity: 3; Iritis: -; Erythema: 0; Chemosis: 1;

Animal2: Opacity: 3; Iritis: -; Erythema: 0; Chemosis: 1;

The application of the test substance caused after 10 minutes slight chemosis, necrosis and corneal opacity. Therefor a precise evaluation of erythema and iritis scores was not possible. The effects were not reversible within 5 weeks (animal1). Severe corneal opacity is considered to be an irreversible effect to ophthalmic tissue.

Interpretation of results:

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

Conclusions:

The test substance induced irreversible effects on the eye.

Executive summary:

An eye irritation test was performed in two Vienna White rabbits. 50 μl of the test substance were applied to the conjunctival sac of one eye in 2 animals. The eyes were not washed out after 24 hours. The animals were observed after 10 min, 1 h and 3 h on the day of treatment and up to 5 weeks afterwards. The application of the test substance caused after 10 minutes slight chemosis, necrosis and corneal opacity. Therefor a precise evaluation of erythema and iritis scores was not possible. The effects were not reversible within 5 weeks in animal 1.

The mean scores of eye irritation (24, 48 and 72 h) were for both animals: Opacity: 3; Iritis: not possible to examine; Erythema: 0; Chemosis: 1. The test substance induced irreversible effects on the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Local effects on skin, eye and respiratory tract were observed in several in vivo studies, which revealed that the test item is corrosive to skin already after 1 min of application (Cat. 1A) and causes severe eye damage. Local effects were also observed in the respiratory tract after acute and repeated inhalation.

Additionally, spontaneous reflectory suppression of the respiration rate, 50 % of normal, caused by sensory irritation in the upper airways (interaction with nerve endings) was observed at exposure concentrations (RD50 values) as low as 260 - 370 mg/m3 (~80 - 120 mL/m3) in mice (Gagnaire et al. 1989/1993; Nielsen et al. 1988). A kind of NOAEC, RD0 value, for inhibition of the respiration rate was found at 36 mg/m3 (12 mL/m3) (Nielsen et al. 1988).

These in vivo findings are in accordance with the observeation that the aqueous solution of the test item (50%) has an extreme pH-value of 13, already indicating the corrosive properties of the substance.

Justification for classification or non-classification

Based on the experimental studies and the extreme pH value of the aqueous solution of the substance a classification as skin corrosive (Cat. 1A), causing severe eye damage and respiratory irritation (STOT SE Cat. 3) is recommended according to Regulation (EC) No. 1272/2008.