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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:
1953
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and similar to OECD guideline 411.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1953
Report Date:
1953
Reference Type:
publication
Title:
Toxicology of Mono, Di, Tripropylene Glycol Methyl Ethers
Author:
Rowe et al.
Year:
1954
Bibliographic source:
Arch Ind Hyg Occup Med, 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): Propylene glycol methyl ether
- Physical state: Colorless liquid
- Analytical purity: 100 %
- Specific gravity: 25/25°C

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
Not specified in the report

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
Route of Administration: dermal
- Area of exposure: Shaved abdomen
- Type of wrap if used: A pad of absorbent cotton about 3"By 3" in size and sufficiently thick to just absorb the volume of the test material was applied to the shaved abdomen of the rabbit. The proper dose of the compound was added to the cotton and then covered with an impervious saran film about 5" by 5".This saran film was covered with a heavy cloth and the whole application was then strapped onto the animal with adhesive tape.



Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not specified in the report
Duration of treatment / exposure:
90 days
Frequency of treatment:
5 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2 ml/kg (1838 mg/kg)
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
4 ml/kg (3676 mg/kg)
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
7 ml/kg (6433 mg/kg)
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
10 ml/kg (9190 mg/kg)
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5 animals/control, 2 ml/kg- 6 animals, 4 ml/kg- 7 animals, 7 ml/kg- 9 animals, 10 ml/kg- 11 animals
Control animals:
yes
Details on study design:
Post-exposure period: no data
- Rationale for animal assignment : Random
- Post-exposure recovery period : None

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No data
DERMAL IRRITATION (if dermal study): No
BODY WEIGHT: Yes
FOOD CONSUMPTION: Yes
HAEMATOLOGY: Yes
Time schedule for collection of blood: Prior to exposure and on day 30th and 90 th.
URINALYSIS: No

Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
On 90th day the rabbits were autopsied and tissues were taken from the liver, kidney, spleen, adrenal, heart, lungs and occasionally from stomach for histological examination. These sections were stained with hematoxylin and eosin.
Other examinations:
Organ weights: At autosy weights of liver, kidney, adrenal, spleen, lungs and heart.
Statistics:
The possible significance between mean cell counts, body weights and organ weights was determined by use of student's test of "t".

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
not specified
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
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:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY: The mortalities resulting from the repeated applications of PGME to the skin of rabbits for a period 90 days as below.
1/6, 2/7, 8/9 and 11/11 for 2, 4, 7 and 10 ml/kg respectively. The higher doses i.e. 7 ml/kg and 10 ml/kg of PGNME produced narcosis which generally led to the death of the animal. Dose group with 2ml/kg and 4 ml/kg were associated with only slight mortality but that was due to respiratory infection and in no way attributable to exposure of PGME.The animals which showed narcosis during the early portion of the experimental period which disappeared as the applications were repeated. The animals had developed a tolerance for the materials.


BODY WEIGHT AND WEIGHT GAIN: There were no significant differences in body weights between control and treated animals of 2ml/kg and 4 ml/kg dose groups. The animals treated with 7ml/kg and 10 ml/kg dose levels showed terminal loss in body weights probably due to decreased food consumption.

FOOD CONSUMPTION: Food consumption was decreased in the animals of 7ml/kg and 10 ml/kg dose groups.

HAEMATOLOGY: There were no PGME exposure related effects on any of the measured hematology parameters in rabbits.

ORGAN WEIGHTS: There were also no statistically significant differences in organ weights of rabbits exposed to PGME

GROSS PATHOLOGY: Gross examination of animals surviving the 90 day period of treatment, irrespective of dose, revealed normal lungs, heart, liver, kidney, adrenal, testes, stomach and intestines. These organs were also normal grossly in rabbits that became narcotized and died, with the exception that the stomach was usually filled with food and marked distended. This gastric retention appeared to be correlated with the narcotic effect. Occasionally, small hemorrhagic areas were noted in the gastric mucosa of such animals.


HISTOPATHOLOGY: Upon histological examination of tissues from surviving animals, the liver, lung, heart, adrenal, spleen, testes and stomach were within normal limits. Death from narcosis was often related to pneumonia and empyema.Occasionally, pyelonephritis or early interstitial nephritis was observed. Renal tubular necrosis of moderate to marked severity was observed in three rabbits that died from the 7 ml/kg and 10 ml/kg doses of PGME.However, other rabbits that died showed only a slight granular degeneration in the tubules

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 838 mg/kg bw/day
Sex:
male
Basis for effect level:
other: overall effects
Dose descriptor:
LOAEL
Effect level:
3 676 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 the results of this study NOAEL for male rabbits is (2.0 ml/kg) 1838 mg/kg/day and LOAEL for male rabbits is (4.0 ml/kg) 3676 mg/kg/day..
Executive summary:

Four groups of male rabbits each were applied by repeated dermal doses, five days per week of PGME (colorless liquid) for a period of 90 days. A total of 65 daily doses were applied to shaved abdomen of rabbit’s equivalent to 10.0 ml/kg, 7.0 ml/kg, 4.0 ml/kg, and 2.0 ml/kg. A fifth matched group of five male rabbits served as a control group for the experiment.

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

The mortalities resulting from the repeated applications of PGME to the skin of rabbits for a period 90 days as below.1/6, 7/2, 9/8 and 111/11 for 2, 4, 7 and 10 ml/kg respectively. The higher doses i.e. 7 ml/kg and 10 ml/kg of PGNME produced narcosis which generally led to the death of the animal. Dose group with 2ml/kg and 4 ml/kg were associated with only slight mortality but that also due to respiratory infection and in no way attributable to exposure of PGME.The animals which showed narcosis during the early portion of the experimental period which disappeared as the applications were repeated. The animals had developed a tolerance for the materials.

There were no significant differences in body weights between control and treated animals of 2 ml/kg and 4 ml/kg dose groups. The animals treated with 7ml/kg and 10 ml/kg dose level showed terminal loss in body weights probably due to decreased food consumption. Food consumption was decreased in the animals of 7ml/kg and 10 ml/kg dose groups.

There were no PGME exposure related effects on any of the measured hematology parameters in rabbits. There were also no statistically significant differences in organ weights of rabbits exposed to PGME.

Gross examination of animals surviving the 90 day period of treatment, irrespective of dose, revealed normal lungs, heart, liver, kidney, adrenal, testes, stomach and intestines. These organs were also normal grossly in rabbits that became narcotized and died, with the exception that the stomach was usually filled with food and marked distended. This gastric retention appeared to be correlated with the narcotic effect. Occasionally, small hemorrhagic areas were noted in the gastric mucosa of such animals.

Upon histological examination of tissues from surviving animals, the liver, lung, heart, adrenal, spleen, testes and stomach were within normal limits. Death from narcosis was often related to pneumonia and empyema.Occasionally, pyelonephritis or early interstitial nephritis was observed. Renal tubular necrosis of moderate to marked severity was observed in three rabbits that died from the 7 ml/kg and 10 ml/kg doses of PGME.However, other rabbits that died showed only a slight granular degeneration in the tubules.

Based on the results of this study NOAEL for male rabbits is (2.0 ml/kg) 1838 mg/kg/day and LOAEL for male rabbits is (4.0 ml/kg) 3676 mg/kg/day