2-(hydroxymethylamino)ethanol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from review article or handbook

Data source

Reference

Reference Type:

review article or handbook

Title:

ETHANOL, 2-(HYDROXYMETHYLAMINO)(CAS No. 34375-28-5) - Developmental Toxicity/Teratogenicity

Author:

(HPVIS) EPA

Year:

1990

Bibliographic source:

U.S Environmental Protection Agency/ High Production Volume Information System (HPVIS) 1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 83-3 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

In developmental toxicity study, the effect of test substance Ethanol, 2-(hydroxymethylamino) in female Sprague-Dawley rat were evaluated

GLP compliance:

no

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 (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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

- Source: No data available
- Age at study initiation: Approximately 9 weeks
- Diet (e.g. ad libitum):Food ad libitum
- Water (e.g. ad libitum):water ad libitum

Administration / exposure

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

water

Details on 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

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

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data available

Details on mating procedure:

- M/F ratio per cage: 2 females to each male
- Length of cohabitation: cohabitation with a male was continuous until mating was detected
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy A vaginal lavage was examined each morning and the day of detection of sperm in the lavage, or of a copulatory plug in situ, was considered as Day 0 of gestation.
- After … days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data available
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available

Duration of treatment / exposure:

20 days after gestation.
Exposure Period: 6 - 16 days, inclusive of gestation

Frequency of treatment:

Once daily

Duration of test:

20 days after gestation.

Doses / concentrations

Remarks:

0, 100, 250 and 500 mg/kg/day

No. of animals per sex per dose:

Total:100
0 mg/kg bw : 25 female
100 mg/kg bw : 25 female
250 mg/kg bw : 25 female
500 mg/kg bw : 25 female

Control animals:

yes, concurrent vehicle

Details on study design:

Further details on study design
- Dose selection rationale: The dose levels for this study were selected after evaluation of a separate dose
range finding study (IRI Project No. 438026).
- Rationale for animal assignment (if not random): No data available
- Other: No data available

Examinations

Maternal examinations:

Mortality, Clinical sign, body weight, food consumption, gross pathology and histopathology were examined.

Ovaries and uterine content:

corpora lutea graviditatis and implantation sites were examined.

Fetal examinations:

live or death fetal fetus, (after ca. Day 16 of gestation), a late embryonic death (ca Day 12-16) or an early embryonic death (death judged to have occurred prior to ca Day 12) and fetal weight, externally visible abnormalities, visceral and skeletal abnormalities

Statistics:

Maternal body weight gains were analyzed by analysis of variance, treatmentgroups 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 groupvalues.

Indices:

No data available

Historical control data:

No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

not specified

Dermal irritation (if dermal study):

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:

effects observed, treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Maternal developmental toxicity

Number of abortions:

not specified

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Changes in number of pregnant:

not specified

Other effects:

not specified

Details on maternal toxic effects:

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

Food consumption: Reduction in food consumption was observed at 500 mg/Kg bw

Gross pathology: Gastro-intestinal abnormalities were observed at 500 mg/Kg bw

No effect was observed on the dam or conceptus at 250 mg/kg bw

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

food consumption and compound intake

gross pathology

other: No adverse effect observed

2

Dose descriptor:

LOAEL

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

food consumption and compound intake

gross pathology

other: adverse effect observed

Maternal abnormalities

Abnormalities:

not specified

Localisation:

not specified

Results (fetuses)

Fetal body weight changes:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified

Reduction in number of live offspring:

not specified

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

effects observed, treatment-related

Visceral malformations:

effects observed, treatment-related

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Moderately increased incidence of advanced ossification, coupled with a decrease in the incidence of patchy ossification in the fetuses were observed at 500 mg/kg bw as compared to control.

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

skeletal malformations

visceral malformations

other: No effect observed

2

Dose descriptor:

LOAEL

Effect level:

500 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

skeletal malformations

visceral malformations

Fetal abnormalities

Abnormalities:

not specified

Localisation:

other: not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL value of the substance Ethanol, 2-(hydroxymethylamino) for developmental toxicity to fetal is 250 mg/kg bw/day and LOAEL value is 500 mg/kg bw/day.

Executive summary:

In developmental toxicity study, the effect of test substance Ethanol, 2-(hydroxymethylamino) in femaleSprague-Dawleyrat were evaluated. The test substance was administered by oral-gavage in the concentration 0, 100, 250 and 500 mg/kg/day.Under the conditions of this study, no effect was seen on the dam, or conceptus, at dose levels of up to 250 mg/kg/day. There was a moderately increased incidence of advanced ossification, coupled with a decrease in the incidence of patchy ossification in the fetuses at 500 mg/kg/day. Maternal 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.The NOAEL value of the substanceEthanol, 2-(hydroxymethylamino) for developmental toxicity to fetal is 250 mg/kg bw/day and LOAEL value is 500 mg/kg bw/day.