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Administrative data

Description of key information

Respiratory irritation is expected. The reason is the strong irritating/corrosive effect of this substance and related primary, secondary and tertiary aliphatic amines with a similar pKa value.

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:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Method: other: 40 CFR, Parts 160 and 792
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Animal weight at initiation: 2.7 - 3.8 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): animal room; controlled at 65-78°F
- Humidity (%): animal room; controlled at 35-70%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
undiluted
TEST MATERIAL
- Amount applied: 0.5 mL per test side
Duration of treatment / exposure:
- 3 minutes
- and 1 hour
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: no data
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with distilled water
- Time after start of exposure: 3 minutes and 1 hour

SCORING SYSTEM: table contained in OECD 405
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 3 minutes
Score:
4
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hr
Score:
4
Max. score:
4
Remarks on result:
other: necrosis at all treated sites
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hr
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis, eschar formation
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hr
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: necrosis and eschar
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hr
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: eschar at al treated sites
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: day 7
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: eschar, exfoliation at all treated sites
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 3 minutes
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hr
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hr
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hr
Score:
2
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hr
Score:
1.33
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 days
Score:
0.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days

Skin irritation and corrosion was tested in a study that was conducted similar to OECD 405 and under GLP conditions. 0.5 mL of DMBA was applied to two clipped skin sites on each of three Newzealand White rabbits. One site was covered for 3 minutes, while the second site covered (occlusive) for one hour. Following each exposure, the test sites were wiped and immediately graded for dermal reactions. Further readings were made at 1, 24, 48, 72 hours and 7 days post treatment. The findings were scored according the table contained in OECD 405.

 

N,N-dimethyl-n-butylamine produced high-grade erythema (score 4) and necrosis at one hour postdose at the three minute and 1-h exposure sites. The dermal responses progressed to eschar at all sites by 24 hours and persisted to test termination on study day 7.  Very slight to moderate swelling (score 1 - 2) was observed at exposure sites during the first 24 hours postdose. This diminished by test termination. Due to the severe effects no further animals were used. Thus, under the conditions of this test, N,N-dimethyl-n-butylamine produced skin corrosion at the three minute and one hour exposure sites (Siglin, 1989).

 

The study is considered to be valid and suitable for assessment.

 

Interpretation of results:
Category 1A (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
N,N-dimethyl-n-butylamine produced skin corrosion at the three minute and 1-h exposure sites.
Executive summary:

Skin irritation and corrosion was tested in a study that was conducted similar to OECD 405 and under GLP conditions. 0.5 mL of DMBA was applied to two clipped skin sites on each of three Newzealand White rabbits. One site was covered for 3 minutes, while the second site covered (occlusive) for one hour. Following each exposure, the test sites were wiped and immediately graded for dermal reactions. Further readings were made at 1, 24, 48, 72 hours and 7 days post treatment. The findings were scored according the table contained in OECD 405.

 

N,N-dimethyl-n-butylamine produced high-grade erythema (score 4) and necrosis at one hour postdose at the three minute and 1-h exposure sites. The dermal responses progressed to eschar at all sites by 24 hours and persisted to test termination on study day 7. 

Very slight to moderate swelling (score 1 - 2) was observed at exposure sites during the first 24 hours postdose. This diminished by test termination.
 Due to the severe effects no further animals were used.

Under the conditions of this test, N,N-dimethyl-n-butylamine produced skin corrosion at the three minute and one hour exposure sites (Siglin, 1989).

 

The study is considered to be valid and suitable for assessment.

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
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline studies with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.36 +/- 0.41 kg
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Animals were held in isolated animal rooms with filtered air suply, temperature and humidity control
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
Group 1: 24 hrs
Group 2: 15 seconds
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
Group 1: 6 animals; 24 hrs
Group 2: 3 animals; 15 seconds
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Group 2
- Time after start of exposure: 15 seconds

SCORING SYSTEM: Draize (1959); table contained in OECD 405

TOOL USED TO ASSESS SCORE: biomicroscope
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: day 13
Score:
13.3
Max. score:
80
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: unwashed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 13 days
Score:
0
Max. score:
10
Reversibility:
other: iris was not affected at any reading
Remarks on result:
other: unwashed eyes
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 13 days
Score:
7.3
Max. score:
20
Reversibility:
other: redness persisted (score: 1) on day 13 whereas chemosis and discharge were fully reversible. Corneal opacity was not reversible.
Remarks on result:
other: unwashed eyes
Executive summary:

N,N-dimethylbutylamine was considered to be a severe eye irritant, based on the results of a study that was conducted essentially similar to OECD 405. The eye reactions of rabbits were recorded up to 14 days after the application of 0.1 mL of the test substance into the conjunctival sac of rabbits, either for 24 hours (Group 1, 6 animals) or 15 seconds (Group 2, 3 animals; eye washed with water). The eye reactions of Group 1 animals indicated marked reactions of the cornea and conjunctivae, whereas the iris was not affected. The conjunctival reactions were largely reversible by day 13, whereas the corneal lesions persisted until the end of the observation period. (Cox and Botta, 1979).

 

The study is considered to be valid with minor restrictions.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

Skin irritation and corrosion was tested in a study that was conducted similar to OECD 405 and under GLP conditions. 0.5 mL of DMBA was applied to two clipped skin sites on each of three Newzealand White rabbits. One site was covered for 3 minutes, while the second site covered (occlusive) for one hour. Following each exposure, the test sites were wiped and immediately graded for dermal reactions. Further readings were made at 1, 24, 48, 72 hours and 7 days post treatment. The findings were scored according the table contained in OECD 405.

 

N,N-dimethyl-n-butylamine produced high-grade erythema (score 4) and necrosis at one hour postdose at the three minute and 1-h exposure sites. The dermal responses progressed to eschar at all sites by 24 hours and persisted to test termination on study day 7. Very slight to moderate swelling (score 1 - 2) was observed at exposure sites during the first 24 hours postdose. This diminished by test termination. Due to the severe effects no further animals were used. Under the conditions of this test, N,N-dimethyl-n-butylamine produced skin corrosion at the three minute and one hour exposure sites (Siglin, 1989). The study is considered to be valid and suitable for assessment.

Eye irirtation/corrosion

N,N-dimethylbutylamine was considered to be a severe eye irritant, based on the results of a study that was conducted essentially similar to OECD 405. The eye reactions of rabbits were recorded up to 14 days after the application of 0.1 mL of the test substance into the conjunctival sac of rabbits, either for 24 hours (Group 1, 6 animals) or 15 seconds (Group 2, 3 animals; eye washed with water). The eye reactions of Group 1 animals indicated marked reactions of the cornea and conjunctivae, whereas the iris was not affected. The conjunctival reactions were largely reversible by day 13, whereas the corneal lesions persisted until the end of the observation period. (Cox and Botta, 1979). The study is considered to be valid with minor restrictions.


Justification for selection of skin irritation / corrosion endpoint:
Skin corrosion could have been predicted from the pKa value of the free base, and no testing would have been required. The prediction is in line with an existing valid in-vivo study which was selected because it demonstrated corrosion within 3 minutes.

Justification for selection of eye irritation endpoint:
The existing in-vivo study was selected. The same effct level could have been predicted from teh pKa value of the free base.

Effects on skin irritation/corrosion: highly corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Proposed classification: Cat 1A