2,3-epoxypropan-1-ol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 March 1980 to 30 May 1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Not relevant - guideline comparable study conducted according to standard methods by reputable organisation - US National Toxicology Program

GLP compliance:

yes

Remarks:

Laboratory underwent quality assurance audits throughout the course of the study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycidol

IUPAC Name:

Glycidol

Constituent 2

Reference substance name:

Glycidol

IUPAC Name:

Glycidol

Constituent 3

Reference substance name:

2,3-epoxypropan-1-ol

EC Number:

209-128-3

EC Name:

2,3-epoxypropan-1-ol

Cas Number:

556-52-5

Molecular formula:

C3H6O2

IUPAC Name:

(oxiran-2-yl)methanol

Constituent 4

Reference substance name:

2,3-epoxy-1-propanol

IUPAC Name:

2,3-epoxy-1-propanol

Details on test material:

Purity: 94 % (94% pure, containing 1.2% 3-methoxy-l,2-propanediol, 0.4% 3-chloro-1,2-propanediol, 2.8% diglycidyl ether, and 1.1% 2 ,6-dimethanol-
1,4-dioxane
Viscous liquid, colourless
At 25°C, the vapour pressure of glycidol is 0.9 mm mercury

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI.
- Age at study initiation: 7 weeks old
- Weight at study initiation: No information available
- Fasting period before study: Not applicable
- Housing: polycarbonate standard lab cages with Cerex spun -bonded nylon cage filters rats housed in groups of 5 by sex
- Diet (e.g. ad libitum): NIH 07 Rat and Mouse Ration, ad libitum
- Water (e.g. ad libitum): ad libitum standard potable water from automatic watering system
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 40-60%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 3 March 1980 To: 30 May 1980

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Rats-O, 25, 50, 100, 200, or 400 mg/kg bw/day glycidol in distilled water by gavage;
dose volume -rats - 5 mL/kg bw administered on 5 d/wk for 13 weeks

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No information provided

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days/week for 13 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
25, 50, 100, 200 or 400 mg/kg
Basis:

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

Refer to Table 1 below

Positive control:

No information provided

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes

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: No data
- 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

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

OTHER: Reduced sperm motility and testicular atrophy/degeneration were recorded at 25 mg/kg dose and 200mg/kg dose groups respectively.

Sacrifice and pathology:

No information provided

Other examinations:

No information provided

Statistics:

No information provided

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

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

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

All rats that received 400 mg/kg bw died by week 2. 3/10 males and 1/10 females that received 200 mg/kg also died before the end of the study. At 25 mg/kg bw/day, reduced sperm motility and reduced number of sperm in semen from the cauda epididymis was observed. Reduced mean body weights were also observed at 50 mg/kg bw/day. Animals receiving 200mg/kg bw displayed signs of testicular atrophy and degeneration. At 400 mg/kg bw/day, necrosis of the granular cell layer of the cerebellum, demyelination in the medulla of the brain, tubular cell degeneration and/or necrosis of the kidney and lymphoid necrosis of the thymus were observed.

Effect levels

Dose descriptor:

LOAEL

Effect level:

25 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

male/female

Basis for effect level:

other: Lowest dose at which effects on test animals were observed.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

>= 25 mg/kg:  reduced sperm motility; reduced number of sperm in semen from the cauda epididymis;
>= 50 mg/kg:  reduced mean body weights;
200 mg/kg:     3/10 males and 1/10 females died before the end of the study;
>= 200 mg/kg: testicular atrophy and/or degeneration;
400 mg/kg:     all animals died by week 2; necrosis of the granular cell layer of the cerebellum, demyelination in the medulla of the brain,
               tubular cell degeneration and/or necrosis of the kidney, lymphoid necrosis of the thymus

Applicant's summary and conclusion

Conclusions:

In this 13-week gavage study in rats compound-related histologic lesions included necrolysis of the granular cell layer of the cerebellum, demyelination in the medulla of the brain, tubular cell degeneration and/or necrosis of the kidney, lymphoid necrosis of the thymus, and testicular atrophy and/or degeneration.

Executive summary:

In the study conducted in 1990, the test substance Glycidol was examined for its ability to cause toxicity when administered by oral gavage to male and female Fischer 344 rats for 13 weeks. The test substance was administered 5 days a week for 13 weeks at a concentration of 25, 50, ,100, 200 or 400 mg/kg. Ten animals per sex per dose were administered. All rats receiving 400 mg/kg bw died by week 2. 3 out of 10 males and 1 out of 10 females that received 200 mg/kg also died before the end of the study. Reduced sperm motility and a reduction in the number of sperm in semen from the cauda epididymis was observed in the 25 mg/kg dose group. Reduced mean body weights were observed in the 50 mg/kg dose group and testicular atrophy/degeneration was observed in the 200 mg/kg dose group. Based on these results, the test substance should be classified as STOT-RE category 2 with the signal word "Warning" and the hazard statement H373: May cause damage to organs (testicles, brain, kidneys, thymus) through prolonged or repeated exposure via the oral route, in accordance with Regulation EC No. 1272/2008.