Registration Dossier

Administrative data

Description of key information

Diethylhydroxylamine is slightly irritating to rabbit skin and eyes and irritating to the respiratory tract.

Skin irritation

The skin irritation potential of diethylhydroxylamine was evaluated in 3 pre-guideline studies. In 2 studies, no signs of skin irritancy were observed in 6 rabbits following a 4-hour or a 24-hour skin contact with diethylhydroxylamine (Latven, 1975a, 1977d). In the third one (Latven, 1980b), moderate skin irritation without skin corrosion was observed after that 0.5 ml diethylhydroxylamine was applied for 24 hours to the intact and abraded skin of 6 rabbits. Skin thickening and exfoliation of the epidermis persisted longer than the erythema but did not involve the dermis. Therefore, on a weight of evidence basis, diethylhydroxylamine, is considered to be at most a slight skin irritant.

Eye irritation

In 2 pre-guideline studies (Latven, 1975b and 1977e), one-tenth ml of diethylhydroxylamine was placed in the conjunctival sac of one eye of each of six albino rabbits. The resulting irritant reactions were scored periodically until recovery. Diethylhydroxylamine, was slightly irritating to the conjunctivae but does not affect the iris or cornea. Therefore, on a weight of evidence basis, diethylhydroxylamine is concluded to be a slight eye irritant.

Respiratory tract irritation

An acute inhalation toxicity study indicated clinical signs of irritation of the mucosa of the respiratory tract (Terrill, 1986) and in a 28-day inhalation repeated dose toxicity study (Naas, 1996) microscopic changes were noted in the nasal passages of rats. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-guideline study with limited details
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Type of coverage:
occlusive
Preparation of test site:
other: shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
3 days
Number of animals:
6
Details on study design:
One-half ml was applied to one intact and abraded skin site under standard gauze patches on each of six albino rabbits. The entire fur-clipped trunk of each animal was then covered with an  impervious sleeve for a skin-contact period of 24 hours.
Irritation parameter:
erythema score
Basis:
animal: #1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of irritation were discernible at any of the twelve treated skin  sites.
Interpretation of results:
GHS criteria not met
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre guideline study
Qualifier:
according to
Guideline:
other: 49 CFR 173.240
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
no data
Duration of treatment / exposure:
4 hour(s)
Observation period:
3 days
Number of animals:
6
Irritation parameter:
erythema score
Basis:
animal: #1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of skin irritancy were evident in any of the six animals following treatment.
Interpretation of results:
GHS criteria not met
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Preparation of test site:
other: Shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hour(s)
Observation period:
daily for 11 days
Number of animals:
6
Details on study design:
One-half ml of the sample was applied to one intact and one abraded skin site under standard gauze patches on each of six albino rabbits. The entire fur-clipped trunk of each animal was then covered with an impervious sleeve for a skin-contact period of 24 hours. Exposures were terminated by removing the dressings and gently cleansing the treated sites with acetone and water. The animals were then examined daily for  eleven days.
Irritation parameter:
erythema score
Basis:
animal: # 1 to 6
Time point:
24/48/72 h
Score:
< 2
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: Mild erythema (scores 1 or 2) and exfoliation
Irritation parameter:
edema score
Basis:
animal: # 1 to 6
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
INTACT SKIN:
Each of the treated sites was pale gray when exposures were terminated. Mild erythema (scores 1 or 2) appeared on the second day and the surface of the skin became abnormally dry. The erythema gradually waned and flake formation of the surface  horny layer began. Gross exfoliation began about seven days after  treatment; this extended well beyond the treated site.

ABRADED SKIN:
Additional effects were superimposed upon the basic skin reaction described above; these were as follows. (1) The initial gray discoloration persisted for many days and its appearance varied with the degree of secondary erythema. (2) The sites also thickened (hypertrophy, not edema) and (3) became moderately indurated about the third or fourth day. (Flexibility was retained and no signs of corrosivity were discernible at any time). Incisions through these lesions on the eleventh  day revealed the dermis to be viable and intact.
Interpretation of results:
GHS criteria not met
Executive summary:

Moderate skin irritation without skin corrosion was observed after that 0.5 ml DEHA was applied for 24 hours to the intact and abraded skin of 6 rabbits. Skin thickening and exfoliation of the epidermis persisted longer than the erythema but did not involve the dermis.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Preguideline study with limited documentation
Qualifier:
according to
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
72h
Number of animals or in vitro replicates:
6
Details on study design:
One-tenth ml was placed in the conjunctival sac of one eye of each of six albino rabbits. The resulting reactions were scored periodically until recovery.
Irritation parameter:
conjunctivae score
Basis:
animal: #animal 1 to 6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: #animal 1 to 6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: #animal 1 to 6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: #animal 1 to 6
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
The reaction was confined to moderate conjunctival inflammation which dissipated completely within 72 hours. None of the scores was positive at 24 or 48 hours and neither the cornea  nor the iris was effected.

Average scores were as follows:
----------------------------------------------------------
time        cornea          iris           conjunctival
                                    ----------------------  
                                    redness      chemosis
----------------------------------------------------------
10 mins       0               0        >1            1
1 hr          0               0         2            2
2 hrs         0               0         2           >2
3 hrs         0               0         2           >2
4 hrs         0               0         2            2
24 hrs        0               0         1            0
48 hrs        0               0         1            0 
72 hrs        0               0         0            0
----------------------------------------------------------

Interpretation of results:
slightly irritating
Remarks:
Migrated information not classified Criteria used for interpretation of results: EU
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Preguideline study with limited documentation
Principles of method if other than guideline:
Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Not rinsed
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
6
Details on study design:
One-tenth ML was placed in the conjunctival sac of one eye of each of six albino rabbits. The resulting irritant reactions were scored periodically until recovery.
Irritation parameter:
conjunctivae score
Basis:
animal: # 1 to 5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: # 1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
cornea opacity score
Basis:
animal: #l 1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #l 1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
Although all instillations evoked intense pain, the irritant reaction was  limited to mild conjunctival inflammation without chemosis; most of the  treated animals recovered within 24 hours. Neither the cornea nor iris  was effected.

Individual conjunctival redness scores were as follows:
----------------------------------------------------------
                          Rabbit
Time     
----------------------------------------------------------
             #1         #1       #3       #4     #5   #6
 
10 min       >1         >1       >1       >1     >1   >1
1 hr         >1         >1       >1       >1     >1   2
2 hrs         1          1        1       >1     >1   2
3 hrs         1          1        1       >1     <2   2
4 hrs         1          1        1        1     <2   2
24 hrs        0          0        0        0      0   1
48 hrs                                                1
72 hrs                                                0
----------------------------------------------------------

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

No classification for skin irritation and eye irritation according to CLP and GHS criteria.

Skin irritation:

On a weight of evidence approach, DEHA is considered to be at most a slight skin irritant. On this basis and in accordance with Regulation (EC) No 1272/2008, DEHA does not merit classification as skin irritant.

Eye irritation:

On a weight of evidence basis, DEHA is concluded to be a slight eye irritant. On this basis and in accordance with Regulation (EC) No 1272/2008, DEHA does not merit classification as eye irritant.

Respiratory tract irritation:

Clinical signs of irritation of the mucosa of the respiratory tract were seen in an acute inhalation study and microscopic changes in the nasal passages of rats were observed in a 28-day inhalation repeated dose toxicity study. On this basis and in accordance with Regulation (EC) No 1272/2008, DEHA was classified as Specific Target Organ Toxicity (STOT) Single Exposure (SE) Category 3 "irritating to the respiratory tract".