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Description of key information

The effect levels derived from the key studies were: 
oral LD50 (rat): 3562 mg/kg bw  
No acute inhalation toxicity hazard was identified (no mortality in rats exposed to a concentrated vapour atmosphere)

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: Acceptable non-GLP study, comparable to guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
BASF test. The study was conducted before the OECD guideline 401 was first adopted.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: purchased from a breeder (Hagemann)
- Age at study initiation: young adult
- Weight at study initiation (range of group mean values): 170-280 g (males), 160-220 g (females)
- Fasting period before study: 15-20 hours prior to the single administration
- Diet: Herilan MRH-Haltung (H. Eggersmann KG, Germany)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 215, 261, 316, 383, 500 mg/mL
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED:
The concentrations of the dose formulations were adjusted to achieve the same dose volume, 10 mL/kg bw.
Doses:
2150, 2610, 3160, 3830, 5000 mg/kg bw
No. of animals per sex per dose:
5 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the frequency of observations was not reported; body weight was determined once prior to treatment, on days 2-4, day 7 and days 12-13 (only mean values reported)
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of premature decedents
Statistics:
Probit analysis according to Finney (1971)
Reference:
Finney DJ (1971). Probit Analysis. Cabridge University Press, 3rd edition.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 562 mg/kg bw
Based on:
test mat.
95% CL:
3 231 - 3 994
Remarks on result:
other: slope factor: 1.20
Mortality:
The mortality incidences after 14 days were:
0/10 at 2150 mg/kg bw
1/10 at 2610 mg/kg bw
2/10 at 3160 mg/kg bw
6/10 at 3830 mg/kg bw
10/10 at 5000 mg/kg bw
Clinical signs:
other: No clinical signs were noted at 2150 mg/kg bw. Dyspnoea, apathy, stagger, spastic gait, ruffled fur and poor general condition were noted at 2610 mg/kg bw and above. Further clinical signs oberved were abnormal posture and paresis at 3160 mg/kg bw, marked
Gross pathology:
There were no macroscopic abnormalities noted at scheduled necropsy.
Premature decedents showed acute right heart dilatation, acute congestive hyperaemia, diffusely reddened glandular stomach (epithelium) and atony as well as diarrhoeic content of the intestine.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 562 mg/kg bw
Quality of whole database:
The database for acute oral toxicity is complete and is considered to meet the relevant data requirements of REACH.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable non-GLP study
Principles of method if other than guideline:
BASF test (inhalation risk test) according to Smyth et al. (1962). The test demonstrated the toxicity of an atmosphere saturated with vapours of the volatile components of the test item at 20 °C.
Reference:
Smyth HF et al. (1962). Am. Ind. Hyg. Ass. J. 23: 95-107.
GLP compliance:
no
Test type:
other: inhalation hazard test
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: purchased from a breeder
- Age at study initiation: young adult
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Rate of air: 200 L/hour
- System of generating a saturated vapour atmosphere: air was bubbled through a substance column of about 5 cm above a fritted glass disk in a glass cylinder.
- Temperature in air chamber: 20 °C
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
Saturated atmosphere, enriched with the volatile fraction of the test item
No. of animals per sex per dose:
6 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: group-wise documentation of clinical signs was performed; body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
other: saturated atmosphere
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: no effects
Mortality:
There were no deaths.
Clinical signs:
other: No clinical signs were observed.
Body weight:
No data
Gross pathology:
There were no macroscopic findings.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The database for acute inhalation toxicity is complete and is considered to meet the relevant data requirements of REACH.

Additional information

Acute toxicity: via oral route

In an acute oral toxicity study (BASF AG, 1980; 78/823), groups of 5 Sprague Dawley rats/sex were given a single oral gavage dose of Kauramin-Härter CE 5196 flüssig, i.e. Bis[(2 -hydroxyethyl)ammonium] sulfite, in distilled water at doses of 2150, 2610, 3160, 3830 or 5000 mg/kg bw (dose volume: 10 mL/kg bw) and observed for 14 days. Mortality incidence, clinical signs and body weights were assessed during the observation period. All survivors were necropsied at the end of the observation period. Oral administration of the test item resulted in 0/10, 1/10, 2/10, 6/10 and 10/10 deaths at 2150, 2610, 3160, 3830 and 5000 mg/kg bw, respectively. Dyspnoea, apathy, stagger, spastic gait, ruffled fur and poor general condition were seen at 2610 mg/kg bw and above. There were no relevant effects on body weights. Survivors showed no test item-related macroscopic findings at scheduled necropsy. Under the conditions of this study, the combined oral LD50 for male and female rats was determined to be 3562 mg/kg bw (95 % C.I.: 3231 to 3994 mg/kg bw).

This assessment is supported by acute oral toxicity studies in rats conducted with the read-across source chemicals (Methylaminoethanol, 2 -Aminoethanol, Sodium sulfite, Disodium disulfite) which form the same cation[aq]/anions[aq] as Bis[(2 -hydroxyethyl)ammonium] sulfite in aqueous solutions, e.g. in biofluids (please refer to the read-across statement/data matrix in section 13). In acute oral toxicity studies conducted with the read-across source chemicals in rats, oral LD50 values of 1089 or 1515 mg/kg bw for 2 -Aminoethanol (Union Carbide Corporation, 1988; 51 -86 and BASF AG, 1966; XV/305), 1880 mg/kg bw for Methylethanolamin (BASF AG, 1965), 2610 mg/kg bw for Sodium sulfite (BASF AG, 1981; 81/311) and 1540 mg/kg bw for Disodium disulfite (Hoechst AG, 1987; 87.1374) were established. This confirms the generally low acute oral toxicity hazard of the salt Bis[(2 -hydroxyethyl)ammonium] sulfite and its dissociation products.

Acute toxicity: via inhalation route

In an acute inhalation risk test (BASF AG, 1980; 78/823) based on a concentrated vapour inhalation method (Smyth et al., 1962), 6 rats/sex were exposed to a maximum vapour concentration of Kauramin-Härter CE 5196 flüssig, i.e. Bis[(2 -hydroxyethyl)ammonium] sulfite, for 7 hours and observed for 7 days. Mortality, clinical signs and body weights were assessed. Survivors were necropsied at the end of the observation period. Under the conditions of this study, no mortality, no clinical signs and no macroscopic findings were noted. Thus, inhalation of a concentrated vapour of the test item did not pose an acute risk to animal's health.

Similarly, when rats were exposed to the maximum attainable concentrations of the source chemicals 2 -Aminoethanol and Methylethanolamin as a vapour (Union Carbide Corporation, 1988; 51 -86; BASF, 1965) or Sodium sulfite as a dust/aerosol (BASF AG, 1982; 81/311) no mortality or signs of systemic toxicity were observed. The weight of evidence indicates that, for the inhalation route, the health hazard exerted by the target chemical Bis[2 -hydroxyethyl)ammonium] sulfite is low.

Acute toxicity: via dermal route (read across)

No data are available on the acute dermal toxicity of Bis[(2 -hydroxyethyl)ammonium] sulfite. In an acute dermal toxicity study (Union Carbide Corporation, 1988; 51 -86), groups of 5 New Zealand White rabbits/sex were given a single dermal application of the neat source chemical 2 -Aminoethanol at doses of 1, 2 or 4 mL/kg bw (1018, 2036 or 4072 mg/kg bw) for 24 hours under occlusive conditions. The animals were then observed for 14 days. Mortality incidence, clinical signs and body weights were assessed during the observation period. All survivors were necropsied at the end of the observation period. The mortality incidences were 0/10, 2/10 and 9/10 at 1, 2 and 4 mL/kg bw, respectively. Dermal exposure with the test item resulted in local clinical signs including erythema, edema and necrosis observed at all dose levels which is consistent with the corrosive properties. Clinical signs of systemic toxicity were noted at all dose levels; these signs included sluggishness, emaciation and/or abdominal distension (not all findings mentioned). There was no effect of treatment on the body weights. At necropsy, red discoloration was noted in all dose groups (lungs, kidneys, intestine). Under the conditions of this study, the dermal LD50 was 2504 mg/kg bw. In a supporting acute dermal toxicity study (Bioassay GmbH, 2009; 11A0250/089092), 5 Wistar rats/sex received a single dermal application of the source chemical Sodium sulfite at the limit dose level of 2000 mg/kg bw. The exposure duration was 24 hours under semiocclusive conditions. No relevant test item-related findings were noted during the 14 -day observation period with respect to mortality, clinical signs and body weights. No macroscopic abnormalities were observed on the day of scheduled necropsy. Under the conditions of this supporting study, the dermal LD50 of Sodium sulfite was >2000 mg/kg bw. Methylaminoethanol was applied once for 24 hours to the clipped skin of the back and flank (area about 50 cm²) of rabbits in a dose of 2000 mg/kg (BASF Ag, 1981). After 24 h, soft anemic necrosis, severe edema, and pea-size 3 mm deep ulcers were observed. LD50 was higher than 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
The key study was selected for the assessment of the acute oral toxicity hazard since it provides reliable data on the target chemical.

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected for a qualitative assessment of the acute inhalation toxicity hazard since it provides reliable data on the target chemical.

Justification for classification or non-classification

Considering acute toxicity data of the source chemicals idenitifed for read-across assessment (section 13), 2 -Aminoethanol is currently classified as Xn; R20/21/22 according to Directive 67/548/EEC (DSD) and as Acute Tox 4; H332, H312, H302 according to Regulation (EC) No 1272/2008 (CLP/GHS). Methylaminoethanol is classified as Xn, R21/22 according to Directive 67/548/EEC (DSD) and as Acute Tox 4; H312, H302 according to Regulation (EC) No 1272/2008 (CLP/GHS). Disodium disulfite is classified as Xn; R22 and Acute Tox 4 based on Directive 67/548/EEC and Regulation (EC) No 1272/2008, respectively.

Referring to the acute toxicity effect levels identified for Bis[(2 -hydroxyethyl)ammonium] sulfite, the substance is not subject to classification for acute toxicity according to Directive 67/548/EEC and Regulation (EC) No 1272/2008. According to UN GHS criteria, classification proposal is Acute Tox Cat 5, H303. The criteria for specific target organ toxicity after single exposure (STOT SE) are not met.