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Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted similar to OECD guideline 410.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Principles of method if other than guideline:
Method: other
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): Dipropylene Glycol Monomethyl Ether
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state:
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 170-240 gms
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:


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


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
other: occlusive and open
Vehicle:
water
Details on exposure:
Route of Administration: dermal
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not specified in the publication
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
4 hours/day; 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 1000 mg/kg/d(occlusive and open)
Basis:
nominal per unit body weight
No. of animals per sex per dose:
8/sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: None

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: No

DERMAL IRRITATION (if dermal study): No

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes


FOOD EFFICIENCY: No data


WATER CONSUMPTION: No data


OPHTHALMOSCOPIC EXAMINATION: No



HAEMATOLOGY: Yes


CLINICAL CHEMISTRY: Yes

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
At the postmortem examination, fragments of bone marrow were removed from the left femur of each rat and placed in tubes containing one drop of 20 % bovine serum albumin in saline. The tubes were placed on a vortex mixer for a few seconds to disperse the marrow fragments. Marrow films were then prepared, air dried and fixed in solvent methanol before staining for 10 min each in May-Grunwald and Giemsa stains. The films were then differentiated for 10 min in dilute phosphate buffer and blotted dry. Additionally one femur from each animal was decalcified with a 10 % solution of formic acid in formalin for 1 week and processed and stained with hematoxylin and eosin.
HISTOPATHOLOGY: Yes
At 28 days, all the rats were killed by intraperitoneal injection of pentobarbitone sodium. The animals were examined post-mortem and testes weighed. Samples of liver, kidney, skin, stomach, small and large intestine and testes were taken for histological processing. Additionally lungs were processed where there was evidence gross abnormality. After fixation in neutral buffered formalin, 5µm sections were cut and stained with hematoxylin and eosin
Other examinations:
Organ weights
Statistics:
The differences between body weight gain, food intake, clinical chemistry, hematology and bone marrow film data between test and control groups were analyzed using the unpaired student t-test to compare values in a test group with those in the corresponding control group at the same stage of the study. Thus combined weight of both testes was used in the analysis in which the weight of both testes animals from test animals was compared with that from the corresponding control animals, with the unpaired student t-test. Histological data were analyzed Fischer's test.

Results and discussion

Results of examinations

Clinical signs:
not specified
Dermal irritation:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
no effects observed
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 specified
Details on results:
CLINICAL SIGNS AND MORTALITY: All animals were survived during 28 day exposure period.

BODY WEIGHT AND WEIGHT GAIN: There were no significant differences in body weights between control and exposed animals


FOOD CONSUMPTION: There were no significant differences in food consumption between control and exposed animals


HAEMATOLOGY: There were no statistically significant differences from control values with respect to hematology.

CLINICAL CHEMISTRY: There were no statistically significant differences from control values with respect to clinical chemistry.

ORGAN WEIGHTS: There were no statistically significant differences organ weights of rats exposed to DPGME


GROSS PATHOLOGY: Macroscopic examination of the tissues revealed no significance findings attributable to DPGME exposure in rats


HISTOPATHOLOGY: NON-NEOPLASTIC: Macroscopic examination of the tissues revealed no significance findings attributable to DPGME exposure in rats


Effect levels

Dose descriptor:
NOEL
Effect level:
> 1 000 mg/kg bw/day
Sex:
male
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on results of the study NOEL for rats via dermal route was >1000 mg/kg/day.
Executive summary:

Wistar rats (8 animals/sex/dose) were exposed to 0,100 and 1000 mg/kg/day (occluded and open) of DOWANOL DPM (colorless liquid) 5 days/week for 28 days.

Monitored for effects included clinical observations, body weights, food consumption, hematology, blood chemistry and, necropsy, organ weights, gross pathology and histopathology.

All animals were survived during 28 day exposure period.There were no significant differences in body weights, food consumption between control and exposed animals.There were no statistically significant differences from control values with respect to hematology and clinical chemistry DPGME exposed rats.

Macroscopic and microscopic examination of the tissues revealed no significance findings attributable to DPGME exposure in rats.

Based on results of the study NOEL for rats via dermal route was > 1000 mg/kg/day.