Registration Dossier

Administrative data

Description of key information

The skin sensitizer potential of diethylhydroxylamine was evaluated in a test performed according to the Buehler method (Shapiro, 1989).After establishing the highest non-irritating dose concentration, a 3 week induction period was initiated during which 10 young adult, male, guinea pigs were treated with diethylhydroxylamine applied as a 30% w/w solution in deionized water and 10 were treated with 0.08% dinitrochlorobenzene (DNCB) in 95% ethyl alcohol (positive controls).During the induction period the animals were dosed on alternate days until a total of nine dose applications was achieved. Seventeen days after the ninth application a challenge dose (30%) was applied to a naive site on each guinea pig and approximately 24 and 48 hours later the animals were scored for a sensitization response (erythema and edema). By the 4th induction many diethylhydroxylamine -treated animals exhibited very mild erythema at both 24 and 48 hours post-dose. A slight increase in the severity of irritation was noted at several sites after inductions 8 and 9. In positive control animals (0.08% DNCB), varying degrees of erythema were observed throughout induction, increasing in severity toward the end of this period. No irritation was noted after challenge in diethylhydroxylamine-treated animals.and naive control animals. In positive control animals, 24 and 48 hours after challenge all sites were erythemic, showing a faint to moderate response.It was concluded that diethylhydroxylamine was not a skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The test was not validated at the time the Buehler assay was performed.
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, S Brunewick, NJ, USA
- Age at study initiation: no data
- Weight at study initiation: 285-394 g
- Housing: gang-caged in suspended stailess cages with mesh floor
- Diet: ad libitum:
- Water: ad libitum
- Acclimation period: 4 or 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67-77 °F
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
30%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50%
No. of animals per dose:
10 treated + 5 control
Details on study design:
After establishing the highest non-irritating dose concentration, a 3 week induction period was initiated during which 10 young adult, male, guinea pigs were treated with the test material applied as a 30% w/w solution in deionized water and 10 were treated with 0.08% Dinitrochlorobenzene (DNCB) in 95% ethyl alcohol (positive controls). During the induction period the animals were dosed on alternate days until a total of nine dose applications was achieved. Seventeen days after the ninth application a challenge dose was applied to a naive site on each guinea pig and approximately 24 and 48 hours later the animals were scored for a sensitization response (erythema and edema). A naive control group of five animals was maintained under the same environmental conditions and was treated with the test material at challenge only.
Positive control results:
The positive response to 0.08% DNCB (positive control) validates the test system used in this study.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30%
No. with + reactions:
0
Total no. in group:
5
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
30%
No. with + reactions:
0
Total no. in group:
5
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.08%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.08%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
not determinable

All guinea pigs appeared active and healthy throughout the
test period. There were no signs of gross toxicity, adverse
pharmacologic effects or abnormal behavior. All animals
gained weight.

INDUCTION PHASE : 
. Test Animals: By the 4th induction many animals exhibited
very mild erythema at both 24 and 48 hours post-dose. A
slight increase in the severity of irritation was noted at
several sites after inductions 8 and 9.
. Positive Control Animals (0.08% DNCB): Varying degrees of
erythema were observed throughout induction, increasing in
severity toward the end of this period.

CHALLENGE PHASE:
. Test Animals: No irritation was noted after challenge.
. Naive Control Animals: No irritation was noted after
challenge.
. Positive Control Animals (0.08% DNCB): Twenty-four and 48
hours after challenge all sites were erythemic, showing a
faint to moderate response.
The incidence and severity of irritation (sensitization
response) after challenge are described below:

                                Sensitization Response
                         
                        -----------------------------------
                            Incidence            Severity
                          -------------       -------------
                          24 hrs.  48 hrs.    24 hrs. 48 hrs.

Test Animals               0/10      0/10         0          0
Positive Control Animals   10/10     10/10        1.5        0.85
Naive Animals              0/5       0/5          0          0
-----------------------------------------------------------------

Interpretation of results:
GHS criteria not met
Conclusions:
Based on these findings Pennatop PF 1866 is considered to be a non contact sensitizer when applied as a 30% w/w solution in deionized water, 3 times a week for 3 weeks.
Executive summary:

The skin sensitizer potential of diethylhydroxylamine was evaluated in a test performed according to the Buehler method (Shapiro, 1989).After establishing the highest non-irritating dose concentration, a 3 week induction period was initiated during which 10 young adult, male, guinea pigs were treated with diethylhydroxylamine applied as a 30% w/w solution in deionized water and 10 were treated with 0.08% dinitrochlorobenzene (DNCB) in 95% ethyl alcohol (positive controls).During the induction period the animals were dosed on alternate days until a total of nine dose applications was achieved. Seventeen days after the ninth application a challenge dose (30%) was applied to a naive site on each guinea pig and approximately 24 and 48 hours later the animals were scored for a sensitization response (erythema and edema). By the 4th induction many diethylhydroxylamine -treated animals exhibited very mild erythema at both 24 and 48 hours post-dose. A slight increase in the severity of irritation was noted at several sites after inductions 8 and 9. In positive control animals (0.08% DNCB), varying degrees of erythema were observed throughout induction, increasing in severity toward the end of this period. No irritation was noted after challenge in diethylhydroxylamine-treated animals.and naive control animals. In positive control animals, 24 and 48 hours after challenge all sites were erythemic, showing a faint to moderate response.It was concluded that diethylhydroxylamine was not a skin sensitizer.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitization: No classification according to CLP and GHS criteria.

In a test performed following the Buehler's method, DEHA was not a skin sensitizer. On the basis of this study and in accordance with Regulation (EC) No 1272/2008, DEHA does not merit classification as skin sensitizer.