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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 June - 15 August 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed and reported guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.8%

Test animals

Species:
rat
Strain:
other: Hoe: WISKf (SPF 71)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Pharma Forschung Toxikologie
- Age at study initiation: males 45 days; females 40 days
- Weight at study initiation: males 158-189 g, females 158-191 g
- Housing: in groups of 3 or 4 animals in Makrolon type-3 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Altromin R 1324 pellets ad libitum
- Water (e.g. ad libitum): Community tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 50 +/- 20 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 27.06.1984 To: 15.08.1984

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: n.a.
Details on inhalation exposure:
Exposure period: 14 days
Recovery period: 36 days
Control group: Yes, concurrent to treatment (air)
Method: OECD 412 (OECD 1981)

10 males and 10 females were used per group (whole body exposure).
Ethylene glycol dimethyl ether was applied to a vaporizer and continuously evaporated at 80°C. The resulting test substance/air mixture was carried to the inhalation chambers (2.25 m3) using an air stream of 800 L/h. The Ethylene glycol dimethyl ether concentration was determined by a Miran 80 photometer every 30 min. CO, CO2 (Uras 2 T Infrared-Gasanalysator) and O2 (Magnos 3 magnetic Oxygen-Analysator) concentration as well as humidity (Transmitter HMT 12) and temperature (CMR-Meßumformer TEU 320) were determined continuously.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Please refer to "Details on inhalation exposure"
Duration of treatment / exposure:
6 hours/d
Frequency of treatment:
5 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
10 ppm (0.037 mg/L)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
50 ppm (0.187 mg/L)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
250 ppm (0.935 mg/L)
Basis:
analytical conc.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
Animals were observed for mortality and clinical symptoms once before each exposure, several times during exposure, once after each exposure and daily during the recovery period. Body weights were recorded before treatment and weekly during the study, food and water consumption were determined weekly. Haematological examination (haemoglobin concentration, reticulocyte count, haematocrit, erythrocyte count, leucocyte count, thrombocyte count, differential blood count, thromboplastin time, Heinz body count, activated partial thromboplastin time and clotting time) and clinical biochemistry (sodium, potassium, bilirubin, creatinine, glucose, urea nitrogen, calcium, chloride, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, cholesterol, total serum protein, meth-haemoglobin, lactate dehydrogenase, phosphorus, lipids, electrophoresis) were performed in 10 animals per group (5 males and 5 females) one day after the last exposure and in the remaining animals 36 days after the last exposure. 10 rats of each dose group (5 males and 5 females) were sacrificed 1 day after the last treatment and the remaining animals 36 days after the last exposure and examined for gross macroscopical changes. Heart, spleen, lung, liver, kidney, brain, testis, ovary, seminal vesicle, adrenal, pituitary gland and thyroid gland were weighed and the relative organ weight was calculated. Full histopathology was carried out on numerous organs and tissues.
Positive control:
None

Examinations

Observations and examinations performed and frequency:
Clincal observations, body weight, food/water consumption, haematology, clinical biochemistry, ophthalmoscopy, organ weights, gross macroscopy, histology
For details please refer to "Details on study design"
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Please refer to "Details on study design"
Statistics:
no data

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):
effects observed, treatment-related
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
Mortality/Viability:
All animals survived and no clinical signs were noted at any dose level. No neurological or ophthalmological effects or changes in mucosa were noted.
Body weight:
Body weight gain of all animals was not affected.

Food/water consumption:
There were no effects upon the mean daily food consumption observed at all dose levels. Water consumption of all females of the 50 ppm dose group was decreased from day 29 until termination of the study. Water consumption of all females of the 250 ppm dose group was decreased on study day 22 and 50.

Haematology:
There were no changes noted at any dose level.

Clinical biochemistry:
All determined parameters were within the control range.

Organ weights:
Relative organ weights were within the control range.

Macroscopic/microscopic findings:
No changes occurred at any dose level with the exception of the reduction of cell layers of seminiferous epithelium in male rats of the 250 ppm dose group. This effect was reversible. There were no such findings in the recovery group.

Effect levels

Dose descriptor:
NOEC
Effect level:
0.187 mg/L air (analytical)
Sex:
male
Basis for effect level:
other: slight changes in the seminiferous epithelium, no changes in female rats at all doses

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on the observed slight changes in the seminiferous epithelium in male rats of the 250 ppm dose group, the NOEC is considered to be 50 ppm (0.187 mg/L). No effects were observed in female animals at any dosage.
Executive summary:

A 14 day inhalation toxicity study was performed in rats. The animals were exposed to an Ethylene glycol dimethyl ether atmosphere of 0, 10 (0.037 mg/L), 50 (0.187 mg/L) and 250 ppm (0.935 mg/L).All animals survived and no clinical signs were noted at any dose level. No neurological or ophthalmological effects or changes in mucosa were noted. Body weight gain of all animals was not affected. There were no effects upon the mean daily food consumption observed at all dose levels. Water consumption of all females of the 50 ppm dose group was decreased from day 29 until termination of the study. Water consumption of all females of the 250 ppm dose group was decreased on study day 22 and 50. There were no haematological changes noted at any dose level.All determined clinical parameters were within the control range. Relative organ weights were within the control range.

No changes occurred at any dose level with the exception of the reduction of cell layers ofseminiferous epithelium in male rats of the 250 ppmdose group. This effect was reversible. There were no such findings in the recovery group.