2-(hydroxymethylamino)ethanol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from USEPA HPV report

Data source

Reference

Reference Type:

review article or handbook

Title:

Repeated dose dermal toxicity 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 F 82-3

Principles of method if other than guideline:

13 weeks repeated dose toxicity (dermal) study of Ethanol, 2-(hydroxymethylamino) was conducted in Sprague-Dawley rats according to US EPA Pesticide Assessment Guidelines Subdivision F, 82-3.

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

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): 2-(hydroxymethylamino)ethanol
- Molecular formula : C3H9NO2
- Molecular weight :91.11 g/mole
- Substance type: Organic
- Physical state:Liquid
- SMILES: OCCNCO

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: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

Distilled water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in distilled water to give a dose range of 0, 50, 250 or 1000 mg/Kg bw

TEST SITE
- Area of exposure: No data
- % coverage: 10% of the total body surface area
- Type of wrap if used: occlusive dressing held in place by means of nonirritating tape.
- Time intervals for shavings or clipplings: No data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): No data
- Constant volume or concentration used: No data
- For solids, paste formed: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

USE OF RESTRAINERS FOR PREVENTING INGESTION: No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

13 Weeks

Frequency of treatment:

6hr/d, 5d/wk (Monday - Friday)

Doses / concentrations

Remarks:

0, 50, 250, 1000 mg/kg/day

No. of animals per sex per dose:

Total: 80
0 mg/Kg: 10 males and 10 females
50 mg/Kg: 10 males and 10 females
250 mg/Kg: 10 males and 10 females
1000 mg/Kg: 10 males and 10 females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: No data
- 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 available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available

DERMAL IRRITATION (if dermal study): Yes, inflammation, dermal fibrosis, epithelial hyperplasia and ulceration was noted
- Time schedule for examinations: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: No data available

FOOD CONSUMPTION: yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Y No data available

FOOD EFFICIENCY: No data available
- 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 available

WATER CONSUMPTION: Yes
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before treatment commenced and during Week 12 of the study
- Dose groups that were examined: 0 and 1000 mg/Kg

HAEMATOLOGY: Yes
- Time schedule for collection of blood: during Week 13
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined.: Hemoglobin, total red blood cell count, total white blood cell count, differential white cell count, hematocrit, calculations of absolute indices, and Hepato Quick test (on sample obtained by tail snip without anesthesia)

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: during Week 13
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. blood urea nitrogen, glucose, aspartate aminotransferase, alanine aminotransferase, sodium, potassium, calcium, chloride, total protein, albumin, albumin-globulin ratio, alkaline phosphatase, Creatinine, phosphate, total bilirubin.

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

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

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, After 13 weeks of dosing all rats were killed and necropsied and adrenals, kidneys, liver, ovaries (with fallopian tubes), testes (plus epididymides) were weighed

HISTOPATHOLOGY: Yes, animals from the control group and 1000 mg/Kg underwent histopathological examination of a comprehensive list of tissues. Rats from 50 and 250 mg/Kg dose groups had only lungs, liver, kidneys and skin sections examined.

Tissues examined in situ and fixed: Adrenals, aortic arch, any abnormal tissue, bladder, bone (sternum and rib), brain, eyes, femur, heart, intestine (duodenum, jejunum, ileum, caecum, colon, rectum), kidneys, liver, lungs (perfused), mammary gland, mesenteric lymph node, muscle (thigh), nasal cavity, esophagus, ovaries (with fallopian tubes), pancreas, pituitary, prostate, sciatic nerve, seminal vesicles, skin (normal), skin (treated), spleen, stomach (glandular and nonglandular), spinal cord (cervical, thoracic and lumbar portions), submaxillary salivary gland, submandibular lymph node, testes (plus epididymides), thymus, thyroids, tongue, trachea, uterus

Other examinations:

No data available

Statistics:

Hematology, clinical chemistry, organ weight and body weight data were statistically analysed for homogeneity of variance using the F-max test. If the group variances appeared homogeneous a parametric ANOVA was used and pairwise comparisons made via Student\s t-test using Fischer's F-protected LSD. If the variances were heterogeneous, log or square root transformations were used in an attempt to stabilize the variances. If the variances remained heterogeneous, then a non-parametric test such as Kruskal-Wallis ANOVA was used and pairwise comparisons made via Dunn Z test where considered appropriate.

Organ weights were also analyzed conditional on body weight (i.e. analysis of covariance).

Histopathology data were analayzed using Fischer's Exact Probability test.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

mortality observed, non-treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

no effects observed

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

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

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:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality:
Clinical signs: There were no notable intergroup differences. The most notable clinical signs included scabbing on and yellow staining around the dosing site, which were seen in all dose groups that received the test material.
Mortality: There was one premature death (male at 250 mg/kg/day dose), which was not considered due to treatment with the test material.

Dermal Irritation: No data available

Body weight and weight gain: There were no consistent dose related effects seen in body weight gain.

Food consumption and compound intake: There were no notable intergroup differences in food consumption

Food efficiency: No data available

Water consumption and compound intake: There were no notable intergroup differences in water consumption

Opthalmoscopic examination: There were no abnormal opthalmoscopic findings

Haematology: There were no notable hematological intergroup differences.

Clinical chemistry: No data available

Urinanalysis: No data available

Neurobehaviour: No data available

Organ weights: No detailed data available

Gross pathology: No detailed data available

Histopathology: No detailed data available

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effect observed for clinical signs, body weight, food and water consumption and opthalmology parameters 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 Ethanol, 2 (hydroxymethylamino) is 1000 mg/kg/day when applied dermally to male and female Sprague-Dawley rats.

Executive summary:

13 weeks repeated dose toxicity (dermal) study of Ethanol, 2-(hydroxymethylamino) was conducted in Sprague-Dawley rats according to US EPA Pesticide Assessment Guidelines Subdivision F, 82-3. The test chemical was dissolved in distilled water and used at dose levels of 0, 50, 250 or 1000 mg/Kg. The chemical was applied daily (Monday – Friday) at a constant volume of 2 ml/kg over an area of approximately 10% of the total body surface area. The treated area was protected for approximately 6 hours by an occlusive dressing held in place by means of nonirritating tape. The animals were observed for mortality, clinical signs, changes in body weight, water and food consumpton, opthamological, hematological and clinical chemistry signs were recorded and the animals underwent gross and histo- pathology. There was one premature death (male at 250 mg/kg/day dose), which was not considered due to treatment with the test material. No dose related changes in body weight, water and food consumption, ophthalmology and no notable hematological intergroup differences were noted. The most notable clinical signs included scabbing on and yellow staining around the dosing site was observed, which were seen in all dose groups that received the test material. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for Ethanol, 2 (hydroxymethylamino) is 1000 mg/kg/day when applied dermally to male and female Sprague-Dawley rats.