2-(methylamino)ethanol, compound with sulphur dioxide

Endpoint summary

Description of key information

The effect levels derived from the key studies were: 
oral LD50 (rat): 3891 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, similar to OECD 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 (Wiga)
- Age at study initiation: young adult
- Weight at study initiation (range of group mean values): 200 g (males), 160-180 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, 316, 383, 464, 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, 3160, 3830, 4640, 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 2-5 (males) or 2-4 (females), 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 891 mg/kg bw

Based on:

test mat.

95% CL:

3 418 - 4 338

Remarks on result:

other: slope factor: 1.26

Mortality:

The mortality incidences after 14 days were:
0/10 at 2150 mg/kg bw
2/10 at 3160 mg/kg bw
5/10 at 3830 mg/kg bw
7/10 at 4640 mg/kg bw
9/10 at 5000 mg/kg bw

Clinical signs:

other: Dyspnoea, apathy and poor general condition were seen at all dose levels. Exsiccosis, ruffled fur, markedly yellow urine and atony were observed at 3160 mg/kg bw and above. Further clinical findings included diarrhoea at 3160 mg/kg bw, spastic gait at 316

Gross pathology:

There were no macroscopic abnormalities noted at scheduled necropsy.
Premature decedents showed acute left and right heart dilatation, pulmonary edema, partial inflation of the lungs, single cases of reddened glandular stomach (epithelium) and atony and diarrhoeic content of the intestine as well as peripheral marks on liver lobules.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 891 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 hazard test) according to Smyth et al. (1962). The test demonstrates 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 substance

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: There were no effects.

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical signs.

Body weight:

No data

Gross pathology:

There were no test substance-related 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, 1979; 77/938), groups of 5 Sprague Dawley rats/sex were given a single oral gavage dose of Kauramin-Härter CE 5162 flüssig, i.e. 2 -(Methylamino)ethanol, compound with Sulfur dioxide, in distilled water at doses of 2150, 3160, 3830, 4640 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 substance resulted in 0/10, 2/10, 5/10, 7/10 and 9/10 deaths at 2150, 3160, 3830, 4640 and 5000 mg/kg bw, respectively. Dyspnoea, apathy and poor general condition were observed at all dose levels. Exsiccosis, ruffled fur, markedly yellow urine and atony were observed at 3160 mg/kg bw and above. There were no relevant effects on body weights. Survivors showed no test substance-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 3891 mg/kg bw (95 % C.I.: 3418 to 4338 mg/kg bw).

This assessment is supported by acute oral toxicity studies in rats conducted with the read-across source chemicals 2 -(Methylamino)ethanol, Sodium sulfite and Disodium disulfite, which form the same cation[aq]/anions[aq] as 2 -(Methylamino)ethanol, compound with Sulfur dioxide, in aqueous solutions, e.g. in biofluids). In acute oral toxicity studies conducted with the read-across source chemicals in rats, oral LD50 values of 1880 mg/kg bw for 2 -(Methlyamino)ethanol (BASF AG, 1965; XV/126), 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 2 -(Methylamino)ethanol, compound with Sulfur dioxide, and its dissociation products.

Acute toxicity: via inhalation route

In an acute inhalation risk test (BASF AG, 1979; 77/938) based on a concentrated vapour inhalation method (Smyth et al., 1962), 6 rats/sex were exposed to a saturated atmosphere of Kauramin-Härter CE 5162 flüssig, i.e. 2 -(Methylamino)ethanol, compound with Sulfur dioxide, 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 substance 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 -(Methylamino)ethanol as a vapour for 8 hours (BASF AG, 1965; XV126) or Sodium sulfite as a dust/aerosol for 4 hours (BASF AG, 1982; 81/311) no mortality or relevant signs of systemic toxicity were observed. This indicates that, for the inhalation route, the acute health hazard exerted by the target chemical 2 -(Methylamino)ethanol, compound with Sulfur dioxide, is low.

Acute toxicity: via dermal route (read across)

No data are available on the acute dermal toxicity of 2 -(Methylamino)ethanol, compound with Sulfur dioxide. In an acute dermal toxicity study (BASF AG, 1981; 79/561), groups of 3 Sprague Dawley rats/sex were given a single dermal application of the neat source chemical 2 -(Methylamino)ethanol at a dose level of 2000 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. Treatment with the test substance resulted in no premature deaths. Aneamic/parchment like necrosis was noted at the application sites. Clinical signs of systemic toxicity included dyspnea, apathy, tumbling, salivation, vocalisation and poor general condition. Slight body weight loss and only marginal body weight gain were noted in male and female animals, respectively, during the first days of the observation period. At necropsy, no macroscopic abnormalities were noted. Under the conditions of this study, the dermal LD50 was >2000 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. Since both substances exhibit corrosive properties and have an LD50 value higher than 2000 mg/kg, it can be expected that treatment to 2 -(Methylamino)ethanol, compound with Sulfur dioxide which has only irritating properties, will also not lead to acute dermal toxicity.

References

Smyth HF, Carpenter CP, Weil CS, Pozzani UC and Striegel JA (1962). Range-finding toxicity data: List VI. Am Ind Hyg Assoc J 23: 95 -107.

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 -(Methylamino)ethanol is currently classified as Xn; R21/22 according to Directive 67/548/EEC (DSD) and as Acute Tox 4; H312, H302 as well as STOT SE 3; H335 according to Regulation (EC) No 1272/2008 (CLP/GHS). Disodium disulfite is classified as Xn; R22 and Acute Tox 4; H302 based on Directive 67/548/EEC and Regulation (EC) No 1272/2008, respectively.

Referring to the acute toxicity effect levels identified for 2 -(Methylamino)ethanol, compound with Sulfur dioxide, 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.