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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic 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 peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Repeated dose oral toxicity study of the test chemical
Author:
Smyth et al
Year:
1955
Bibliographic source:
Journal of the American pharmaceutical association

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
The sub acute (90 days) study was conducted to evaluate the toxic effects of repeated administration of the test chemical to rat by the oral diet route.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
EC Number:
500-038-2
EC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Cas Number:
25322-68-3
Molecular formula:
(C2-H4-O)mult-H2-O
IUPAC Name:
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Details on test material:
- Name of test material (as cited in study report): Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: N/A
- Age at study initiation: N/A
- Weight at study initiation:N/A
- Fasting period before study:N/A
- Housing:N/A
- Diet (e.g. ad libitum):N/A
- Water (e.g. ad libitum):N/A
- Acclimation period:N/A

ENVIRONMENTAL CONDITIONS
- Temperature (°C): N/A
- Humidity (%):N/A
- Air changes (per hr):N/A
- Photoperiod (hrs dark / hrs light):N/A

IN-LIFE DATES: From: To:N/A

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
Dose group : Fed PEG 400 equivalents to 2000,4000,8000,16000,24000 mg/kg/day (2%, 4%, 8%, 16%, 24% respectively) PEG in the diet.
Control group : Fed diet without polyethylene glycol.

DIET PREPARATION
The diet consisted of 60 parts of freshly ground whole wheat, 30.5 parts of dried whole milk, 1.5 parts of dried liver extract U. S. P., 5.0 parts dried inactive brewers' yeast, 1 part calcium carbonate, and 2 parts iodized table salt.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0,2000,4000,8000,16000 and 24000mg/kg/day
Basis:
nominal in diet
No. of animals per sex per dose:
Control: 5 males and 5 females
2000 mg/kg/day:5 males and 5 females
4000 mg/kg/day:5 males and 5 females
8000 mg/kg/day:5 males and 5 females
16000 mg/kg/day:5 males and 5 females
24000mg/kg/day:5 males and 5 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Not examined

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 (body weight as a ratio to the amount of nutrient consumed was recorded.)

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: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not examined

OPHTHALMOSCOPIC EXAMINATION: Not examined

HAEMATOLOGY: Not examined

CLINICAL CHEMISTRY:Not examined

URINALYSIS: Not examined

NEUROBEHAVIOURAL EXAMINATION: Not examined

Organ weight : Liver weight, kidney weight were examined during the study period.

Mortality : Mortality effects was studied.
Sacrifice and pathology:
HISTOPATHOLOGY: Yes
Micro pathology of liver and kidney was examined.
Statistics:
It is indicated in the study data was subjected to statistical methods with a 1 in 19 level of significance.

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Decrease in weight gain of either sex in terms of grams per 100 Gm. nutrients eaten.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effect was observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
At dose concentration 16000 mg/kg/day kidney and liver were heavier than that of control rats.
Gross pathological findings:
not examined
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
During a 90-day period, effects were studied such as mortality, appetite, body weight both in grams and as a ratio to the amount of nutrient consumed, liver weight, kidney weight, and micro pathology of liver and kidney but no effects were observed up to 8000 mg/kg/day.

Effect levels

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Dose descriptor:
NOAEL
Effect level:
8 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Body weight as a ratio to the amount of nutrient consumed, body weight; liver weight, kidney weight; micro pathology of liver and kidney.
Dose descriptor:
LOAEL
Effect level:
16 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Body weight as a ratio to the amount of nutrient consumed, body weight; liver weight, kidney weight; micro pathology of liver and kidney.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a sub acute repeated dose toxicity study, the test chemical showed no effect upon male and female rats when it was present in the diet at a dose level upto 8000 mg/kg/day (8% concentration) during a 90 days study period. But at 16000 mg/kg/day, the test chemical showed effects on organ weight (liver and kidney heavier than that of control rats);and a Decrease in weight gain was observed.

Thus the NOAELs (no observed adverse effect level) for repeated dose oral toxicity was considered to be 8000 mg/kg/day whereas the LOAELs (low observed adverse effect level) for subacute repeated dose was considered to be 16000 mg.kg/day.
Executive summary:

The study was designed to investigate the subacute repeated dose toxicity effects of the test chemical in Wistar rats (male/female) by oral route, in an overall study period of 90 days. Dose group (5 animals per group) was fed a solution of PEG400 equivalent to 0, 2000, 4000, 8000, 16000 or 24000 mg/kg/day in the diet. The control group received no test chemical. During the study period, body weight as a ratio to the amount of nutrient consumed, body weight,liver weight, kidney weight, micro pathology of liver and kidneyswere examined. No effects upon male and female rats were observed when the test chemical was present in the diet at a level up to 8000 mg/kg/day (8%concentration) for 90 days study period. But at 16000 mg/kg/day it showed effects on organ weight (liver and kidneyheavier than that of control rats);and a decrease in weight gain was observed. Thus, from overall conclusion of the study the NOAEL (no observed adverse effect level) for repeated dose oral toxicity was considered to be 8000 mg/kg/day. And the LOAEL (low observed adverse effect level) for subacute repeated dose toxicity was considered to be 16000 mg/kg/day.