Dibutylamine

Endpoint summary

Description of key information

Irritation/corrosion:
- skin corrosion: Cat. 1B
- eye damage: Cat 1

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

BASF-Test: Corrosion-Test (3 min and 1 hour exposure); 2 animals were treated for 3 minute and 2 other animals for 1 hour using occlusive conditions. An application site of 2 x 2 cm was covered with the liquid test substance (0.5 ml). After the application time, the skin was washed with lutrol (conc.) or Lutrol/water (1:1). The animals were observerd for 8 days and skin changes were recorded daily.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler M., Offenbach, Germany
- Weight at study initiation: 1 hour-test: 3.2 kg (mean); 3 minute-test: 2.8 kg (mean)
- Diet: Sniff standard diet for rabbits and guinea pigs, supplied by INTERMAST GmbH, Soest, Germany, ad libitum
- Water ad libitum

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin site of the same animals served as control.

Amount / concentration applied:

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

Duration of treatment / exposure:

3 min, 1 hour

Observation period:

8 days

Number of animals:

1 male and 1 female

Details on study design:

TEST SITE
- Area of exposure: 2 x 2 cm
- Type of wrap if used: rubberized linen


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 3 minutes, 1 hour

Irritation parameter:

erythema score

Remarks:

, 3 min exposure

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Remarks:

, 1 h expsoure

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Remarks:

, 3 min exposure

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

edema score

Remarks:

, 1 h exposure

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Mean erythema score after 24 h, 48 h and 72 h (animal1/2):

Exposure time	24 h	48 h	72 h	mean
3 min	4/4	4/4	4/4	4/4
1 h	4/4	4/4	4/4	4/4

Mean edema score after after 24 h, 48 h and 72 h (animal1/2):

Exposure time	24 h	48 h	72 h	mean
3 min	2/2	2/2	2/2	2/2
1 h	2/2	2/2	2/2	2/2

The 3 min and 1 h exposure caused severe erythema and slight to moderate edema. After 24 h necrosis was observed. At the end of the observation period of 8 days leathery necrosis was observed. Leathery like necrosis is considered as a full thickness necrosis.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

3 min and 1 h exposure caused severe erythema and slight to moderate edema. After 24 h necrosis was observed. At the end of the observation period of 8 days leathery necrosis was observed. Leathery like necrosis is considered as a full thickness necrosis.

Executive summary:

In a skin irritation study, Vienna White rabbits were treated with the undiluted test substance. 2 animals were treated for 3 minutes and 2 other animals for 1 hour using occlusive conditions. An application site of 2 x 2 cm was covered with the liquid test substance (0.5 ml). After the application time, the skin was washed with lutrol (conc.) or Lutrol/water (1:1). The animals were observerd for 8 days and skin changes were recorded daily. 3 minutes as well as 1 hour of exposure caused severe erythema and slight to moderate edema. After 24 h necrosis was observed. At the end of the observation period of 8 days full thickness necrosis was observed.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable report which meets basic scientific principles.

Qualifier:

no guideline followed

Principles of method if other than guideline:

0.5 ml of the sample was applied to one intact and one abraded skin site under standard gauze patches on each of three albino rabbits. The entire hair-clipped trunk of each animal was then covered with an impervious sleeve for a skin-contact period of 24 h. The animals were observed for seven days after treatment.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

7 days

Number of animals:

3

The sample spread beyond the intended sites of contact and caused pain in every instance. The skin turned brown within 15 min. 24 h after initial contact, all treated sites consisted of large (4 cm) necrotic lesions. These become dry, hard and concave within 48 h. Subsequently they began to crack and peel, exposing raw tissue.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The test substance was applied to the skin of three albino rabbits for 24 h. The sample spread beyond the intended sites of contact and caused pain in every instance. The skin turned brown within 15 min. 24 h after initial contact, all treated sites consisted of large (4 cm) necrotic lesions. These become dry, hard and concave within 48 h. Subsequently they began to crack and peel, exposing raw tissue.

Executive summary:

0.5 ml of the sample was applied to one intact and one abraded skin site under standard gauze patches on each of three albino rabbits. The entire hair-clipped trunk of each animal was then covered with an impervious sleeve for a skin-contact period of 24 h. The animals were observed for seven days after treatment.

The sample spread beyond the intended sites of contact and caused pain in every instance. The skin turned brown within 15 min. 24 h after initial contact, all treated sites consisted of large (4 cm) necrotic lesions. These become dry, hard and concave within 48 h. Subsequently they began to crack and peel, exposing raw tissue.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

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

Duration of treatment / exposure:

no data

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

4

Details on study design:

not rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 h

Score:

>= 0.8 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

The test substance produced severe ocular irritation which persisted through Day 7 in two of the four animals. Responses seen at 24 hours included severe conjunctival irritation (redness, chemosis, discharge, necrosis), iridial changes or iritis and corneal opacity, stippling and ulceration and corneal bulging (indicative of increased intraocular pressure). By Day 7, two of the four animals still exhibited conjunctival irritation, iridial changes and corneal opacity, stippling and/or ulceration, corneal bulging and pannus (neovascilarization of the corneal surface). The other two animals exhibited only slight conjunctival irritation and/or iridial changes and stippling which were reversible after 7 d.

Interpretation of results:

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

Conclusions:

4 rabbits were treated with 0.1 ml of the unchanged test substance (without rinsing) and observed for 7 days. The test substance produced severe ocular irritation which persisted through Day 7 in two of the four animals.

Executive summary:

4 rabbits were treated with 0.1 ml of the unchanged test substance (without rinsing) and observed for 7 days.

The test substance produced severe ocular irritation which persisted through Day 7 in two of the four animals. Responses seen at 24 hours included severe conjunctival irritation (redness, chemosis, discharge, necrosis), iridial changes or iritis and corneal opacity, stippling and ulceration and corneal bulging (indicative of increased intraocular pressure). By Day 7, two of the four animals still exhibited conjunctival irritation, iridial changes and corneal opacity, stippling and/or ulceration, corneal bulging and pannus (neovascilarization of the corneal surface). The other two animals exhibited only slight conjunctival irritation and/or iridial changes and stippling which were reversible after 7 d.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data only given as summary tables but acceptable for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Eye injury in rabbits is recorded in a 10-grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical, as detailed by Carpenter and Smyth. Grade 1 in the Table indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Vehicle:

other: propylene glycol or water

Controls:

not specified

Amount / concentration applied:

Concentration: 1 % active substance
Amount applied: 0.5 ml

Duration of treatment / exposure:

24 hour(s)

Observation period (in vivo):

24 hours

Number of animals or in vitro replicates:

5

Details on study design:

not rinsed

Injury grade 9 on a 10-grade scale 24 h after application: corresponds to corrosiveness (62 - 87 % of cornea with necrosis).

Ranking system not quite evaluable as to current standards, but strong effect reflects "corrosiveness".

Interpretation of results:

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

Conclusions:

Rabbits were treated with the test substance for 24h. Result shows an injury grade of 9 after 24h of application. This corresponds to corrosiveness (62 - 87 % of cornea with necrosis). Ranking system not quite evaluable as to current standards, but strong effect reflects "corrosiveness".

Executive summary:

5 albino rabbits were treated with 0.5 mL of 1% active test substance in the vehicles propylene glycol or water (without rinsing) for a treatment and observation period of 24h. Eye injury in rabbits is recorded in a 10-grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical, as detailed by Carpenter and Smyth. Grade 1 in the Table indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol. Result shows an injury grade of 9 after 24h of application. This corresponds to corrosiveness (62 - 87 % of cornea with necrosis). Ranking system not quite evaluable as to current standards, but strong effect reflects "corrosiveness".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a primary skin irritation study with the undiluted test material a 3 min and 1 h exposure caused severe erythema and slight to moderate edema. After 24 h necrosis was observed. At the end of the observation period of 8 days full thickness necrosis was observed (1978; K2). Corrosive effects to skin were also found in two other studies where only limited data is provided (1954; K2; 1976; K2). In two studies according to Draize, a single 4 h dermal application of 0.5 ml of the compound was made on clipped intact skin sites on the backs of albino rabbits (1973; 1975; K2). After 4 h severe erythema, edema and necrosis persisting through 72 h were observed. Furthermore, a Corrositex Biobarrier Membrane was used to determine the skin irritation / corrosion potential of the test substance in vitro. Results show that the test substance belong to the packing group III (effetcts after 1 -4 hours) (1993; K2). Due to the precautional principle, the test substance in classified as skin corrosive Cat. 1B.

Eye irritation:

0.1 ml of the test substance produced severe ocular irritation which persisted through Day 7 in two of the four animals (1985; K2). Responses seen at 24 hours included severe conjunctival irritation (redness, chemosis, discharge, necrosis), iridial changes or iritis and corneal opacity, stippling and ulceration and corneal bulging (indicative of increased intraocular pressure). By Day 7, two of the four animals still exhibited conjunctival irritation, iridial changes and corneal opacity, stippling and/or ulceration, corneal bulging and neovascularization of the corneal surface. The other two animals exhibited only slight conjunctival irritation and/or iridial changes and stippling which were reversible after 7 d. In a second study 100 µl was placed in the conjunctival sacs of both eyes of each of three albino rabbits (1976; K2). One eye of each animal was washed with flowing water initiated 15 seconds after instillation and continued for a period of one minute. The contralateral eye remained unwashed. Reactions in washed and unwashed eyes were identical. Severe conjunctival inflammation together with mild iridal congestion developed promptly (in one animal mild corneal clouding, score 2, appeared in both eyes four days after treatment). A publication confirmed these effects (1954; K2). Due to the precautional principle, the test substance in classified as eye damaging Cat. 1.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The test substance is considered to be classified for skin corrosion Cat. 1B amd for eye damage Cat. 1 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.