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Administrative data

Description of key information

Oral route

In a pre-guideline study, groups of 5 WBS/W rats were administered dose levels of 1400, 2000, 2800, 4000 mg/kg bw of diethylhydroxylamine (undiluted) by stomach tube (Latven, 1977a). The animals were then observed for 7 days following exposure. At 4000 mg/kg, 5/5 rats died, at 2800 mg/kg bw 4/5 rats died, at 2000 mg/kg bw, 2/5 rats died and at 1400 mg/kg bw none died. Clinical observations revealed muscular incoordination and general depression. Autopsy findings were negative. The LD50 was 2190 mg/kg bw.

In a pre-guideline study, groups of 2, 5 or 10 male OF1 mice were administered dose levels of 875, 1000, 1300, 1800, 2400, 3200, 4300, 8750 mg/kg bw of diethylhydroxylamine by stomach tube (Latven, 1957). The animals were then observed for 7 days following exposure. No mortality was observed at 875, 1000 and 1300 mg/kg bw, at 1800 mg/kg, 2/10 mice died, at 2400 mg/kg bw 7/10 mice died, at 3200 mg/kg bw, 10/10 mice died and at 4300 and 8750 mg/kg bw 2/2 mice died. Clinical observations revealed decrease motor activity, ataxia, complete inactivity, muscular hypotonicity, loss of righting reflex, muscular spasms, mild clonic convulsions, respiratory depression, cyanosis and death. The LD50 was 2150 mg/kg bw.

Inhalation route

In an acute inhalation toxicity study performed according to the US EPA guideline (Terrill, 1986), series of groups consisting of five male and five female Sprague-Dawley derived rats was exposed to diethylhydroxylamine vapor for four hours mean analytical levels in the range of 1410 to 4720 parts per million (ppm). At 1410 and 2650 ppm, no rat died, 3240 and 3560 ppm, 1/5 male and 5/5 female rats died, and at 4720 ppm, all rats died. The mortality results indicated the test material was more lethal to female rats than to male rats. Signs attributable to treatment included death, increased incidences of secretory responses, respiratory distress, general signs of poor condition, corneal opacity and loss of body weight. Overall, the time-to-onset and time-to-recovery of these signs were related to exposure concentration. The lungs of numerous animals, both treated and control, were discoloured primarily scattered red-grey foci were observed in the animals which were killed at the end of the study, whereas in the animals which died, the lungs were bright to dark red. The toxicologic significance of these findings, if any, cannot be determined on the basis of a gross examination only. The LC50 was determined 4400 ppm for the males, 2620 ppm for the females and 3140 ppm for both sexes combined.

Dermal route

In a pre-guideline study, groups of 4 albino rabbits were treated dermally under a pre-fitted occluding sleeve with 707, 1000, 1414 and 2000 mg/kg body weight of diethylhydroxylamine (Latven, 1980a). The occluding sleeve was removed 24 hours following exposure and the animals were observed for 7 days. No rabbit died at 707 mg/kg/bw, at 1000 mg/kg bw, 1/4 rabbit died, at 1414 mg/kg bw, 2/4 rabbits died and at 2000 mg/kg bw, all rabbits died. The clinical signs observed were hypersensitivity, mydriasis, and incoordination prior to toxic incapacitation. The acute dermal LD50was 1300 mg/kg bw.

In two other pre-guideline studies (Latven, 1977 and 1979), groups of three albino rabbits were treated dermally with a single dose of 2000 mg/kg (2.24 ml/kg) diethylhydroxylamine and three additional rabbits were treated with a single dose of 200 mg/kg (2.0 ml/kg of a 10% W/V aqueous dilution). Individual doses were applied to the fur-clipped skin of the trunk under a pre-fitted impervious sleeve on each of the animals. After a skin-contact period of 24 hours, the sleeves were removed and in one study (Latven, 1979) the treated sites were gently cleansed with a 2% solution of acetic acid. Surviving animals were then observed for seven days. All animals died at 2000 mg/kg bw and none at 200 mg/kg bw.

 


Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-guideline study with limited details
Principles of method if other than guideline:
Pre-guideline study
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: WBS/W
Sex:
male
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
1400, 2000, 2800, 4000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
Sex:
male
Dose descriptor:
LD50
Effect level:
2 190 mg/kg bw
Based on:
test mat.
Mortality:
Oral dose(mg/kg) No.rats(dead/total) mortality time for death (hours)
1400 0/5 -
2000 2/5 -, -, -, >5, >24
2800 4/5 -, >3, >5,>24,>24
4000 5/5 >2, 5, 5, >5, >5
Clinical signs:
Muscular incoordination and general depression. Autopsy findings were negative.
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Executive summary:

In a pre-guideline study, groups of 5 WBS/W rats were administered dose levels of 1400, 2000, 2800, 4000 mg/kg bw of diethylhydroxylamine (undiluted) by stomach tube. The animals were then observed for 7 days following exposure. At 4000 mg/kg, 5/5 rats died, at 2800 mg/kg bw 4/5 rats died, at 2000 mg/kg bw, 2/5 rats died and at 1400 mg/kg bw none died. Clinical observations revealed muscular incoordination and general depression. Autopsy findings were negative.The LD50was 2190 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 190 mg/kg bw
Quality of whole database:
Pre-guideline study with limited details

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Wilmington, Massachusetts 01887
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: 228-299 g for males, 170-228 g for females
- Fasting period before study: not appropriate
- Housing: doubly-housed in suspended stainless steel wire mesh cages during the first week of the acclimation period and individually during the remainder of the acclimation period and all other non-exposure periods.
- Diet (ad libitum): standard laboratory diet (Purine Rodent Laboratory Chow #5001 or 5002)
- Water (ad libitum): by automated watering system (Elizabethtown Water Company).
- Acclimation period: 2-3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature : 67-76°F
- Humidity (%): 30-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
A series of four-hour whole-body inhalation exposures was performed using  Sprague-Dawley derived rats (5/sex/group) to determine the acute  inhalation toxicity of diethylhydroxylamine. The test substance was  administered into the breathing zone of the animals as vapor. In addition, a group of  control animals (5/sex) received house-supply air only while in chamber.
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The Plexiglas® exposure chamber had a total volume of 100 liters. The chamber was operated dynamically at a calibrated air flow rate of 25 liters per minute (lpm). This flow rate was calculated to provide one complete air change every 4 minutes and a 99% equilibrium time of 18.4 minutes.
- System of generating particulates/aerosols: The test substance was placed in 500 ml bubblers and fitted with impingers. House-supply air was delivered via a Dwyer flowmeter and a Nupro metering valve, to a set of bubblers then into a 3-neck flask containing glass wool. For Group I, II, V, and VI, bubblers were immersed in a waterbath as provided by a Braun Thermomix. For Groups I, II, III, V and VI, additional diluted air was delivered to the 3-neck flask via a Nupro metering valve and a Dwyer flowmeter. For ail groups, the resultant vapor-laden air stream was directed from the 3-neck flask into the 100 liter Plexiglas® exposure chamber. The initial generation airflow rate, dilution airflow rate, total airflow rate, and waterbath temperature settings are summarized as follows:
Group Generation Dilution Total Water-
Airflow bath
Rate Temp.
Airflow Airflow
Rate Rate
I (1pm) (1pm) (1pm) (°C)
7.0 18.0 25.0 60
II 12.5 12.5 25.0 60
III 14.0 11.0 25.0 -
IV 0 25.0 25.0 -
V 12.5 12.5 25.0 40
VI 12.5 12.5 25.0 37
- Method of particle size determination: Samples for particle size distribution assessment of the chamber and room air were drawn once during the first hour. The chamber particle count for all groups was less than five times the background (room air) using the widest channel therefore the aerosol concentration was considered to be negligible and no further measurements were taken for that exposure. Measurements were performed using a Royco Model 227 Portable Particle Monitor. Particle size distribution measurements were not performed for the control group (Group IV).
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Samples for determination of diethylhydroxylamine exposure levels were taken using a MIRAN® lA Amblent Air Analyzer and strip chart recorder. The test atmosphere was drawn through 1/4" Teflon® line at a flow rate of 2.0 liters per minute (lpm) for Groups II, III, V and VI, and at a maximum attainable flow for Groups I and IV (control) by a Dwyer flowmeter and a Nupro metering valve to a glass "Y" tube where, for Groups II, III, V and VI, it was diluted (2:1) with room air. For Groups I and IV, the samples were assayed undiluted. These samples were drawn into the MIRAN® using a Neptune 4K Dyna-pump, once every half-hour during exposure from the normal sampling portal (denoted H-1 in Figures 1-3). In addition, a distribution sample was drawn once from the distribution sampling portal.
The exposure levels of diethylhydroxylamine were determined by comparison of the resultant absorbance to a calibrated response.
- Samples taken from breathing zone: yes/no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: No aerosol was found during any exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1410, 2650, 3240, 3560, 4720 ppm (analytical)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- In-Life Observations:
Day 1 (Day of Exposure): All animais were observed individually, immediately prior to exposure, as a group at approximately fifteen minute intervals during the first hour of exposure, at half-hour intervals for hours 1 and 2 and hourly for the remainder of the exposure period. All survivors were observed individually upon removal from the chamber (half hour after exposure was completed) and four hours post-exposure. Detailed physical observations were recorded at each interval.
Days 2 through 15 (Post-exposure): Detailed observations were recorded for survivors once daily; viability was assessed twice daily.

- Body weight:
Day 1 (immediately prior to exposure) and on Days 2, 3, 4, 8, 11 and 15 (just prior to sacrifice).

- Postmortem:
A complete gross postmortem examination was performed on all animals dying spontaneously during the course of the study as well as those animais surviving to the end of the 14-day post-exposure observation period. The gross postmortem examinations included examination of the nasal passages, trachea, external surface, all orifices, the cranial cavity, carcass, the brain and spinal cord, the thoracic, abdominal and pelvic cavities and their viscera and the cervical tissues and organs.

- Terminal Necropsy:
Post-exposure Day 15.
Statistics:
A calculation of median lethal concentration and 95% confidence limits was performed according to the method of "Litchfield and Wilcoxon''.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3 140 other: ppm (analytical)
95% CL:
2 770 - 3 560
Exp. duration:
4 h
Remarks on result:
other: LC50 = 11.4 mg/l
Sex:
male
Dose descriptor:
LC50
Effect level:
4 400 other: ppm (analytical)
95% CL:
3 410 - 5 880
Exp. duration:
4 h
Remarks on result:
other: LC50 = 16.0 mg/l
Sex:
female
Dose descriptor:
LC50
Effect level:
2 620 other: ppm (analytical)
95% CL:
2 210 - 3 100
Exp. duration:
4 h
Remarks on result:
other: LC50 = 9.5 mg/l
Mortality:
See below
Clinical signs:
other: 1. Exposure Period: Lacrimation, irregular breathing, reduced activity, hunched appearance, matted coat, eyes partially closed, dried red  material around the facial area and/or chromodacryorrhea were observed during exposure. These occurred in many, but
Body weight:
Mean body weights were decreased for both sexes in all test groups compared to control animals on the first day following exposure, and the differences from the control animals seemed to follow a pattern related to exposure concentration. Subsequently, body weight results for all animals except Group V males were considered unremarkable. Group V males had returned to a normal rate of weight gain by the end of the first week post-exposure. Test Week 2 results were considered unremarkable.
Gross pathology:
Numerous tissues and organs of the animals which died during the study  were discolored, primarily various intensities of red. This was not  considered to be unusual in animals which died and were not exsanguinated  prior to postmortem examination.  The lungs of numerous animals, both treated and control, were discolored; primarily scattered red-grey foci were observed in the  animals which were killed at the end of the study, whereas in the animals  which died, the lungs were bright to dark red. The toxicologic  significance of these findings, if any, could not be determined on the  basis of a gross examination on only. Other postmortem findings which  were observed grossly occurred sproradically in the treated and/or control animals and did not appear to be related to the test article.

Chamber Monitoring and Mortality:
The mean analytical and nominal concentrations of
diethylhydroxylamine along with the overall mortality in
each test group are summarized below:
-----------------------------------------------------------
                   Mean
                   Analytical      Nominal        Mortality
  Group            Concentration  Concentration  #dead/#exposed
                   (ppm)           (ppm)      Male   Female
-----------------------------------------------------------
I                  1410            1690        0/5        0/5
II                 4720            5890        5/5        5/5
III                2650            2780        0/5        0/5
IV-Control            0               0        0/5        0/5
V                  3560            4430        1/5        5/5
VI                 3240            4840        1/5        5/5
----------------------------------------------------------
The individual analytical values showed little variation about the mean. For Groups I and III, the nominal and analytical 

values  were approximately the same. For the other
three test groups which were run at higher exposure levels,
the nominal concentrations were somewhat higher than the
analytical values. No reason for these differences between
nominal and analytical values was found. No aerosol was
found during any exposure.
Chamber relative humidity was generally acceptable in all
exposures. Chamber temperature was a few degrees above the
generally acceptable environmental limit (for 24-hour
housing) of 76°F. This environmental condition is considered
to have no effect, upon the conclusion that may be drawn from
the study .

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
A series of groups consisting of five male and five female Sprague-Dawley derived rats was exposed to diethylhydroxylamine vapor for four hours mean analytical levels in the range of 1410 to 4720 parts per million (ppm). Signs attributable to treatment included death, increased incidences of secretory responses, respiratory distress, general signs of poor condition, corneal opacity and loss of body weight. Overall, the time-to-onset and time-to-recovery of these signs were related to exposure concentration. The mortality results indicated the test material was more lethal to female rats than to male rats. The lungs of numerous animals, both treated and control, were discolored primarily scattered red-grey foci were observed in the animals which were killed at the end of the study, whereas in the animals which died, the lungs were bright to dark red. The toxicologic significance of these findings, if any, cannot be determined on the basis of a gross examination only.
Executive summary:

In an acute inhalation toxicity study performed according to the US EPA guideline, series of groups consisting of five male and five female Sprague-Dawley derived rats was exposed to diethylhydroxylamine vapor for four hours mean analytical levels in the range of 1410 to 4720 parts per million (ppm). At 1410 and 2650 ppm, no rat died, 3240 and 3560 ppm, 1/5 male and 5/5 female rats died, and at 4720 ppm, all rats died. The mortality results indicated the test material was more lethal to female rats than to male rats. Signs attributable to treatment included death, increased incidences of secretory responses, respiratory distress, general signs of poor condition, corneal opacity and loss of body weight. Overall, the time-to-onset and time-to-recovery of these signs were related to exposure concentration. The lungs of numerous animals, both treated and control, were discoloured primarily scattered red-grey foci were observed in the animals which were killed at the end of the study, whereas in the animals which died, the lungs were bright to dark red. The toxicologic significance of these findings, if any, cannot be determined on the basis of a gross examination only. The LC50 was determined 4400 ppm for the males, 2620 ppm for the females and 3140 ppm for both sexes combined.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
11 400 mg/m³
Quality of whole database:
GLP guideline study

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-guideline study with limited details
Principles of method if other than guideline:
Pre-guideline study
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Four albino rabbits were used at each of four dosage levels. Individual doses were applied to the fur-clipped skin of the trunk under a pre-fitted occluding sleeve on each animal. The sleeves were renoved 24 hours later and surviving animals were observed for seven days.
Doses:
707, 1000, 1414, 2000 mg/kg
No. of animals per sex per dose:
4
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
95% CL:
995 - 1 690
Mortality:
Skin dose(mg/kg)  No.rabbits(dead/total)   Time for deaths (hours) 

707                     0/4                -   -    -  -  
1000                    1/4                -   -    -  >26
1414                    2/4                -   -   <20, >26
2000                    4/4              <20, <20, <20, >26
Clinical signs:
Hypersensitivity, mydriasis, and incoordination prior to toxic incapacitation.
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
Category 4 based on GHS criteria
Executive summary:

In a pre-guideline study, groups of 4 albino rabbits were treated dermally under a pre-fitted occluding sleeve with 707, 1000, 1414 and 2000 mg/kg body weight of diethylhydroxylamine. The occluding sleeve was removed 24 hours following exposure and the animals were observed for 7 days. No rabbit died at 707 mg/kg/bw, at 1000 mg/kg bw, 1/4 rabbit died, at 1414 mg/kg bw, 2/4 rabbits died and at 2000 mg/kg bw, all rabbits died. The clinical signs observed were hypersensitivity, mydriasis, and incoordination prior to toxic incapacitation. The acute dermal LD50was 1300 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 300 mg/kg bw
Quality of whole database:
Pre-guideline study with limited details

Additional information

Justification for classification or non-classification

Acute oral toxicity:

The oral LD50of DEHA was 2150 mg/kg in rats. On the basis of this study and in accordance with Regulation (EC) No 1272/2008, no classification is warranted with respect to acute oral toxicity.

Acute inhalation toxicity:

The 4 -h LC50of DEHA was 11.4 mg/L in rats. On the basis of this study and in accordance with Regulation (EC) No 1272/2008, DEHA shall be classified as Acute Tox. 4 (Hazard statement: H332; Harmful if inhaled).

Acute dermal toxicity:

The percutaneous LD50of DEHA was 1300 mg/kg in rabbits. On this basis and in accordance with Regulation (EC) No 1272/2008, DEHA shall be classified as Acute Tox. 4 (H312: Harmful in contact with skin).