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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
other: 10 day repeated dose
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to a guideline study design. Ten-day exposure instead of 28-day exposure. Only a single dose used.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
yes
Principles of method if other than guideline:
Ten-day exposure instead of 28-day exposure. Single exposure level.
GLP compliance:
yes (incl. certificate)
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ethoxypropanol
- Physical state: Liquid
- Analytical purity: 91.1%
- Impurities (identity and concentrations):
8.0% 2-ethoxy-1-propanol
0.7% 1-methoxy-2-propanol
0.1% 2-methoxy-1-propanol
0.04% 1-(2-propenyloxy)-2-propanol

- Purity test date: 6 June 1983
- Lot/batch No.: Batch No. 96 from BP Chemie, Lavera
At room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Each animal was uniquely identified by ear notching.

TEST ANIMALS
- Source: Charles River UK Ltd, Kent, England
- Age at study initiation: Approximately 6 weeks of age at receipt
- Weight at study initiation: Males: 255 – 300 g, Females: 170 – 205 g
- Housing: Animals were housed in groups of three or less in polypropylene cages with stainless steel grid tops and floors.
- Diet: Ad libitum access to No. 1 pelleted expanded maintenance diet from Special Diet Services Ltd, Essex, England
- Water: Ad libitum access to water supplied by the North Surrey Water Company
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 – 22.5 degrees C
- Humidity: 37 – 64 % relative humidity
- Air changes: Approximately 15 air changes per hour
- Photoperiod: 14 hour light:10 hour dark cycle

IN-LIFE DATES: From: June 2, 1983 To: June 24, 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
Ten days
Frequency of treatment:
Once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
2 ml/kg/day
Basis:

No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: Based on pilot study conducted as doses of 2 ml/kg and 5 ml/kg.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: Daily

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At necropsy
- Parameters checked in table [No.?] were examined: Erythrocyte count (RBC); Leucocyte count, total (WBC); Haemoglobin (HB); Haematocrit (HCT); Mean Cell Volume (MCV); Mean Cell Haemoglobin (MCH); Leucocyte count, differential (WBC-diff); Reticulocyte count (Retic).

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Each animal was subjected to a detailed macroscopic examination including opening the abdominal, thoracic and cranial cavities. The appearance of all organs was noted in situ and all abnormalities recorded; the cut surfaces of liver and kidneys were examined.

HISTOPATHOLOGY: Yes
Liver, spleen, pancreas, stomach, duodenum, ileum, caecum, lymph nodes, colon, rectal, adrenal, kidney, bladder, prostate, testis, epididymis, seminal vesicle, ovary, uterus, thymus, heart, lung, aorta, trachea, oesophagus, tyroids, salivary glands, eye, Hardarien gland, brain, pituitary, skin, bone, muscle, nerve, spinal cord.
Statistics:
Student’s ‘t’ test to compare group means. When individual variance ratios were significant (P < 0.05), Chochran’s approximation was used.

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
Haematological findings:
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
All animals survived the study. Slight loss of condition, including coat staining and lack of grooming was observed.
BODY WEIGHT AND WEIGHT GAIN
Bodyweight gain was slightly reduced in treated male animals; a transient reduction in body weight gain was observed in treated female rats at the beginning of the study.

HAEMATOLOGY
Small but statistically significant reductions in erythrocyte count, haematocrit and haemoglobin concentration were seen in treated male animals.

ORGAN WEIGHTS
Statistically significant increases in mean absolute and relative liver weights were recorded in treated female rats. Increases in relative liver and testis weights were recorded in treated males. The increase in relative testes weight was considered to be a reflection of the slightly reduced body weight in these animals since the absolute testes weights in these animals were indistinguishable from those of control animals.

HISTOPATHOLOGY: NON-NEOPLASTIC
There were no microscopic findings that were considered to be related to treatment with ethoxypropanol. There were no histopathological findings that could account for the increased liver weights.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The female rat given 5 ml/kg in the pilot study was killed in extremis after receiving a total of 6 doses.  All other animals survived the pilot study.

Applicant's summary and conclusion

Executive summary:

In a 10-day oral gavage study in rats, daily doses of 2.0 ml/kg ethyoxypropanol (the in vivo hydrolysis product of ethoxypropyl acetate) produced a small reduction in the growth rate of male animals and an ungroomed appearance and staining of the fur in both sexes.  Small but statistically significant reductions in erythrocyte count, haematocrit and hemoglobin concentration were seen in treated males.  These changes were not seen in female animals and their toxicological significance is not clear.  Liver weights were increased in both male and female animals, but there were no histopathological findings in these livers. A true NOAEL could not be obtained from this study.