2-(hydroxymethylamino)ethanol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from USEPA HPVIS report

Data source

Reference

Reference Type:

review article or handbook

Title:

Repeated dose oral toxicity study for Ethanol, 2-(hydroxymethylamino) _ (CAS# 34375-28-5)

Author:

US EPA HPV Chemical Challenge Program- Troy Corporation

Year:

2005

Bibliographic source:

U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA Guideline 83-3(a)

Principles of method if other than guideline:

Repeated dose dermal toxicity study was performed to determine the oral toxic nature of Ethanol, 2-(hydroxymethylamino) as per the EPA Guideline 83-3(a)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(hydroxymethylamino)ethanol

EC Number:

251-974-0

EC Name:

2-(hydroxymethylamino)ethanol

Cas Number:

34375-28-5

Molecular formula:

C3H9NO2

IUPAC Name:

2-[hydroxy(methyl)amino]ethanol

Details on test material:

- Name of test material (as cited in study report): Ethanol, 2-(hydroxymethylamino)
- Molecular formula (if other than submission substance): C3H9NO2
- Molecular weight (if other than submission substance): 91.1091 g/mole
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): Purity: 98.5%

Specific details on test material used for the study:

- Name of test material: Troysan 174, (2[(Hydroxymethyl)amino] ethanol)
- IUPAC name: 2-[hydroxy(methyl)amino]ethanol
- Molecular formula: C3H9NO2
- Molecular weight: 91.1091 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: 98.5%
- Impurities (identity and concentrations): 1.5%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

No data

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): Food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%):No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

water

Remarks:

Distilled water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in distilled water to give a dose range of 0, 100, 250 and 500 mg/kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Concentration in vehicle: 0, 100, 250 and 500 mg/kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

Day 6-16 inclusive of gestation (20 days)

Frequency of treatment:

Once daily

Doses / concentrations

Remarks:

0, 100, 250 or 500 mg/Kg/day

No. of animals per sex per dose:

25 Females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dose levels for this study were selected after evaluation of a separate dose range finding study
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
Viability: at the beginning of each day, and again as late as possible on each day
Reaction: Each day
- Cage side observations checked in table [No.?] were included. All the animals were examined for viability at the beginning of each day, and again as late as possible on each day and reaction to
treatment on each day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Specific examinations were made 1-1.5 hours after dosing, during which the nature, onset, duration and intensity of any signs were recorded

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 9, 13, 17 and 20 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, The weight of food consumed by each mated female was recorded daily throughout the study, commencing on Day 4 of gestation
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data - Animals fasted: No data - Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, On Day 20 of gestation, the animals were killed by carbon dioxide asphyxiation. The contents of the thoracic and abdominal cavities were examined
macroscopically for abnormalities

HISTOPATHOLOGY: Yes, The reproductive tract was removed and weighed intact then opened and the contents were examined

Other examinations:

No data

Statistics:

Maternal body weight gains were analyzed by analysis of variance, treatment groups being compared using an F-protected Least Significant Difference (LSD) procedure.

For other parameters no formal statistical analyses were considered necessary, interpretation of the data being based on inspection of the individual and group values.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality: No data

Body weight and weight gain: Reduction in body weight was noted at 500 mg/Kg bw

Food consumption and compound intake: Reduction in food consumption was noted at 500 mg/Kg bw

Food efficiency: No data

Water consumption and compound intake: No data

Opthalmoscopic examination: No data

Haematology: No data

Clinical chemistry: No data

Urinanalysis No data

Neurobehaviour: No data

Organ weights: No data

Gross pathology: No data

Histopathology: Gastro-intestinal abnormalities were noted at 500 mg/Kg bw

Effect levels

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant observations were made in body weight, food consumption and histopathology at the mentioned dose level

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for the test compound Ethanol, 2-(hydroxymethylamino) is 250 mg/Kg bw.

Executive summary:

Repeated dose dermal toxicity study was performed to determine the oral toxic nature ofEthanol, 2-(hydroxymethylamino). The study was performed using 25 female Sprague Dawley rats at dose levels of 0, 250, 500 or 1000 mg/Kg bw. The chemical was dissolved in distilled water. The animals were observed clinical signs, changes in body weight and food consumption, gross and histopathology was performed. Under the conditions of this study, no effect was seen on the rats, at dose levels of up to 250 mg/kg/day. Repeated dose toxicity was observed at 500 mg/kg/day indicated by gastro-intestinal abnormalities, reduced body weight gain and reduced food consumption during the treatment period. Hence theNo Observed Adverse Effect Level (NOAEL) for the test compoundEthanol, 2-(hydroxymethylamino) is 250 mg/Kg bw.