Butyl glycollate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-Jan-05 through 1989-Feb-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl glycollate

EC Number:

230-991-7

EC Name:

Butyl glycollate

Cas Number:

7397-62-8

Molecular formula:

C6H12O3

IUPAC Name:

butyl glycolate

Constituent 2

Reference substance name:

Polysolvan O

IUPAC Name:

Polysolvan O

Constituent 3

Reference substance name:

Glycolic acid-n-butyl ester

IUPAC Name:

Glycolic acid-n-butyl ester

Details on test material:

- Name of test material (as cited in study report): Polysolvan O (butyl glycollate)
- Physical state: liquid
- Analytical purity: about 97.3%
- Impurities (identity and concentrations): 0.1% unknown, <0.1% n-butanol, <0.1% di-n-butyl ether, 0.2% chloro acetic acid-n-butyl ester, 2.1% butoxy acetic acid n-butyl ester; <0.1% di-glycolic acid di-n-butylester, 0.3% water, 0.005% glycolic acid
- Purity test date: 09-Aug-1988
- Lot/batch No.: Laufprobe 09-Aug-1988
- Stability under test conditions: stable
- Storage condition of test material: in the dark, 20 °C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst Kastengrund, Germany
- Age at study initiation: about 6 weeks
- Fasting period before study: none
- Housing: 5/cage
- Diet (e.g. ad libitum): ad libitum, standard chow (Altromin 1324, Lage, Germany)
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 °C
- Humidity (%): 50±20%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light


IN-LIFE DATES: From: 1989-01-05 To: 1989-02-02

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
daily

VEHICLE
- Justification for use and choice of vehicle (if other than water): low solubility in water, high solubility in sesame oil
- Concentration in vehicle: 0, 0.16, 0.8, 4.0, 20.0%
- Amount of vehicle (if gavage): 5 ml/g bw

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

29 days, 28 applications

Frequency of treatment:

daily, prior to application

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 8, 40, 200, 1000 mg/kg bw/day (m/f)
Basis:
other: nominal in sesame oil

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: at start of study and twice/week

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, twice/week

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

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: once/week

OPHTHALMOSCOPIC EXAMINATION: Not required according to guideline

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of treatment
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: 5 m/5 f
- Parameters examined: erythrocytes, hemoglobin, hematocrit, MCV, MCH, MCHC, white blood cells, thrombocytes, differential blood picture, reticulocytes, Heinz bodies (control and high dose group), coagulation time

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of treatment
- Animals fasted: No
- How many animals: 5 m/5 f
- Parameters examined: sodium, potassium, calcium, chloride, inorganic phosphor, total billirubin, billirubin direct, glucose, uric acid, creatinine, urea, protein, ASAT, ALAT, y-GT, alkaline phosphatase, albumin, alpha1-3 globulin, beta1 globulin, y1 globulin, albumin/globulin ration

URINALYSIS: Yes
- Time schedule for collection of urine: at the end of treatment
- Metabolism cages used for collection of urine: No
- Animals fasted: No
- Parameters examined: appearance, color, pH, hemoglobin, protein, glucose, ketones, billirubin, urobilirubin, specific weight

NEUROBEHAVIOURAL EXAMINATION: No: not required

Sacrifice and pathology:

GROSS PATHOLOGY: complete necropsy
ORGAN WEIGHTS: heart, lung, liver, kidney, spleen, testes, adrenal glands
HISTOPATHOLOGY: heart, lung, liver, kidney, spleen, thymus, testes, stomach, small intestine (jejunum), large intestine (colon), bone marrow (femur), adrenal glands

Statistics:

Mean and standard deviation was calculated
Methods: Dunnett, Sidak, followed by Nemenyi

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL CHEMISTRY
at 1000 mg/kg bw(day: slight increase in inorganic phosphor and slight decrease in protein in both sexes

URINALYSIS
at 1000 mg/kg bw/day: slight increase of erythrocytes in sediment in both sexes

Effect levels

1

Dose descriptor:

NOEL

Remarks:

200 mg/kg bw/day

Sex:

male/female

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

2

Dose descriptor:

NOAEL

Remarks:

1000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Slight increase in inorganic phosphor, slight decrease in protein, slight increase of erythrocytes in urine sediment in both sexes. All observed findings are known to be reversible.

Remarks on result:

not measured/tested

Remarks:

Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Body weight (mean)

 

mg/kg bw/day	0	8	40	200	1000
Males
Day 1 (g)	132	128	121	125	130
Day 29 (g)	273	277	260	274	254
Females
Day 1 (g)	119	121	125	120	123
Day 29 (g)	175	180	188	185	183

 

Food consumption (mean)

 

mg/kg bw/day	0	8	40	200	1000
Males
Day 1 (g/day)	17.8	17.0	16.4	16.6	17.6
Day 29 (g/day)	16.4	15.9	15.2	15.5	14.7
Day 1-29 (g/day)	17.3	17.7	16.9	17.4	16.3
Females
Day 1 (g/day)	15.5	15.8	16.7	16.1	15.8
Day 29 (g/day)	10.9	10.0	11.4	10.4	9.2
Day 1-29 (g/day)	12.5	12.3	13.5	13.0	12.5

 

Clinical chemistry (changed parameter, mean)

 

mg/kg bw/day	0	8	40	200	1000
Males
Inorganic phosphor (mmol/L)	2.34	2.38	2.57	2.63	3.18
Protein (g/L)	59	61	56	56	54
Females
Inorganic phosphor (mmol/L)	2.62	2.18	2.64	2.65	3.7
Protein (g/L)	59	60	55	54	51

 

 

Applicant's summary and conclusion

Conclusions:

The no observed effects level (NOEL) for subacute oral (gavage) toxicity in male and female Wistar rats was 200 mg/kg bw/day under the conditions of the study. The top dose level of 1000 mg/kg bw/day can be considered as no observed adverse effect level (NOAEL) as only minor changes were noted, generally accepted to be reversible.

Executive summary:

The subacute oral toxicity of Polysolvan O (butyl glycollate, 97.3%) was investigated in male and female Wistar rats. Each 5 males and 5 females received dose levels of 0, 8, 40, 200 and 1000 mg/kg bw/day by daily gavage during a period of 29 days (28 applications).The test item was dissolved in sesame oil. Mortality, clinical findings and behavior were examined at least once a day, body weight and food consumption was determined twice a week and water consumption once a week. At the end of the application, hematology, clinical chemistry and urinalysis were performed. After sacrifice, a complete necropsy was performed, organ weights were determined and the animals were subjected to histopathology.

 

This study is assessed as appropriate and valid since it was performed according to an internationally accepted testing guideline and according to GLP. Reporting, assessment and data presentation in the study report was considered as appropriate.

 

No animal died prior to schedule and there were no clinical signs of toxicity. No effect was noted for body weight/body weight gain, food/water consumption and hematology. Gross pathology and histopathology revealed no treatment related findings and the organ weights were not affected.

 

Only at the top dose level of 1000 mg/kg bw/day there was a slight increase in inorganic phosphor and slight decrease in protein as well as a slight increase of erythrocytes in urine sediment in both sexes. However, all findings are known to be reversible.

 

The study is considered as acceptable as it was performed according to the OECD guideline 407 (adopted 1981) under GLP conditions.

 

Conclusion:

Polysolvan O (butyl glycollate, 97.3%) was tolerated up to the limit dose level of 1000 mg/kg bw/day without any adverse finding of systemic toxicity. Only isolated minor and reversible changes in clinical chemistry and urinalysis were noted. The NOEL for subacute toxicity was 200 mg/kg bw/day, while the NOAEL can be considered as 1000 mg/kg bw/day for male and female Wistar rats.