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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1950
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1950
Report Date:
1950
Reference Type:
publication
Title:
Toxicology of Mono-, Di-, and Tri-Propylene Glycol Methyl Ethers
Author:
Rowe, V.K., McCollister, D.D., Spencer, H.C. et al.
Year:
1954
Bibliographic source:
Published in AMA Archives of Industrial Hygiene and Occupational Medicine, June 1954, Vol 9: 509-525.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dowanol 50B (Dipropylene Glycol Methyl Ether)
- Physical state: Clear colorless liquid

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
Route of Administration: dermal
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
5 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1 ml/kg
Basis:

Remarks:
Doses / Concentrations:
3 ml/kg
Basis:

Remarks:
Doses / Concentrations:
5 ml/kg
Basis:

Remarks:
Doses / Concentrations:
10 ml/kg
Basis:

No. of animals per sex per dose:
Only male rabbits were used. Total no. of animals used: 29 rabbits
Control group-5
1 ml/kg-5
3 ml/kg-6
5 ml/kg-6
10 ml/kg-7
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes

DERMAL IRRITATION (if dermal study): Yes

BODY WEIGHT: Yes
- Time schedule for examinations: Rabbits were weighed before the application of each daily dose of the test compound.

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

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Control blood counts were taken before the start of the study and on the thirtieth and ninetieth day of the application of the compound.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 29 animals before the start of the study, 30th day-22 and 90th day-20 animals
- Parameters checked in table [No.1] were examined.

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Possible significance between means was studied by students test of "t".

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
no effects observed
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
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:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
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 SIGNS AND MORTALITY
Dowanol 50B at the 10 ml/kg and 5 ml/kg produced some narcosis. However narcosis was not observed at lower dose levels (1.0 and 3.0 ml/kg).
Mortality was high at the 10.0 ml/kg dosage level, slight at 5.0 ml/kg, low at 3.0 ml/kg(1/6) and absent at the 1.0 ml/kg dose level.
BODY WEIGHT AND WEIGHT GAIN
No adverse body weight changes occurred at any level except just prior to death in those animals that succumbed, presumably to the narcotic effects of the top dosage levels.


HAEMATOLOGY
No haematological changes, occurred at any dosage level.


ORGAN WEIGHTS
No significant organ weight changes occurred at any dosage level.

GROSS PATHOLOGY
Observations for gross pathology revealed only gastric distension and occasional gastric irritation in those animals dying at the 10 ml/kg dosage level.

HISTOPATHOLOGY: NON-NEOPLASTIC
Histopathological studies conducted on the liver, lung, spleen, adrenal, heart, testes and stomach of those animals receiving the 5.0 and 10.0 ml/kg dosage levels revealed no changes. The kidneys of those animals on the 10.0 ml/kg level showed some granular and some hydropic changes, at the 5.0 ml/kg same kidney abnormalities were observed but they were of no greater intensity than those observed in some of the controls.


OTHER FINDINGS
The effect of severe (repeated and prolonged) exposure to the skin was slight, being similar to that caused by distilled water under similar conditions. No skin irritation was observed during 90 days of exposure.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 850 mg/kg bw/day (actual dose received)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOEL for dipropylene glycol methyl ether in rabbits following dermal exposure was 2850 mg/kg bw/day under the conditions of this study.
Executive summary:

DOWANOL 50B, the methyl ether of dipropylene glycol, a colorless liquid was evaluated for chronic skin absorption in rabbits.

 

Male rabbits were selected and divided into groups of at least five animals each. Dipropylene glycol methyl ether was applied over the abdominal skin using the following technique. A pad of absorbent cotton about 3”×3” in size and sufficiently thick just to absorb the volume of the test material was applied to the clipped abdomen of the rabbit. The proper dose of the compound was added to the cotton and the pad was then covered with an impervious saran film about 5”×5”. This saran film was covered with a heavy cloth, and the whole application was then strapped onto the animal with adhesive tape. Dipropylene glycol methyl ether was thus applied five times a week over a period of three months at four dosage levels: 1.0, 3.0, 5.0 and 10.0 ml/kg. A separate group of five animals to which distilled water was bandaged served as controls.

 

The rabbits received the stock diet of commercial rabbit chow and water ad libitum. The rabbits were weighed before the application of each daily dose of the test compound. Control blood counts were taken before the start of the study and on the thirtieth and ninetieth day of the application of the compound. Possible significance between means was studied by students test of “t”. On the ninetieth day the rabbits were autopsied and tissues taken from the liver, kidneys, spleen, adrenal, heart, lung and occasionally stomach, for histopathological examination. Such sections were stained with haematoxylin and eosin.

 

Dipropylene glycol methyl ether at the 10 ml/kg and 5 ml/kg produced some narcosis. However narcosis was not observed at lower dose levels (1.0 and 3.0 ml/kg). Mortality was high at the 10.0 ml/kg dosage level, slight at 5.0 ml/kg and absent at the 1.0 and 3.0 ml/kg dose levels.

 

No adverse body weight changes occurred at any level except just prior to death in those animals that succumbed, presumably to the narcotic effects of the top dosage levels.

 

No haematological changes occurred at any dosage level. No significant organ weight changes occurred at any dosage level. Observations for gross pathology revealed only gastric distension and occasional gastric irritation in those animals dying at the 10 ml/kg dosage level.

 

Histopathological studies conducted on the liver, lung, spleen, adrenal, heart, testes and stomach of those animals receiving the 5.0 and 10.0 ml/kg dosage levels revealed no changes. The kidneys of those animals on the 10.0 ml/kg level showed some granular and some hydropic changes, at the 5.0 ml/kg same kidney abnormalities were observed but they were of no greater intensity than those observed in some of the controls.

 

The effect of severe (repeated and prolonged) exposure to the skin was slight, being similar to that caused by distilled water under similar conditions.