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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Acceptable, well documented study which meets basic scientific principles and contains sufficient detail to be able to judge the results reliable as a contribution to the understanding of the toxicity of this substance. Method only provides an approximation of the LD50.

Data source

Reference
Reference Type:
publication
Title:
Comparative toxicological study of ethyl glycol acetate and butyl glycol acetate
Author:
Truhaut R, Dutertre-Catella H, Phu-Lich N, Ngoc Huyen V
Year:
1979
Bibliographic source:
Toxicol Appl Pharmac 51, 117-27

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Modification of the Draize 1959 method using the 'sleeve' technique of Dutertre-Catella(Food Cosmet Toxicol, 16, 177-81, 1978 - in French)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Source: Pfaltz & Bauer, Flushing, NY.
Name: ethylene glycol monobutylether acetate
Purity: no details

Test animals

Species:
rabbit
Strain:
other: New Zealand (unspecified)
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Evic-Ceba, Blanquefort, France
- Fasting period before study: no
- Weights at start of study: 2.2-2.5kg
- Food and water: ad libitum
- Housing: individual
- Acclimation period: 2 weeks

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin
- Type of wrap if used: successive layers of gauze, cotton wool then a sheet of rubber held by bandage then a final sheet of rubber around trunk to avoid leakage

QUANTIFICATION OF TEST MATERIAL USED
The weight difference between the wrapping materials before and after exposure was used to quantify the amount of material absorbed through the skin.
Duration of exposure:
24 hours
Doses:
see table below
No. of animals per sex per dose:
no data
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Weights were recorded before dosing and at the end of the 14-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The presence of blood, protein, glucose, ketone bodies and nitrites in the urine and urine pH was measured with test strips (times not indicated). Red and white blood cells in urine were counted with a Coulter counter. Hemoglobin was also measured. All animals were necropsied upon death. Heart, lungs, liver, spleen, pancreas, kidneys, adrenals, ovaries, bladder, skin, brain and testes were fixed and examined histologically.
Statistics:
The LD50 was determined by the method of Miller and Tainter (Proc Soc Exp Biol Med 57, 261-4, 1944). Because the actual absorbed dose could not be controlled to provide a geometric progression, the method of calculation of LD50 using moving averages could not be used and the determined LD50 is therefore only approximate.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 1 500 mg/kg bw
Remarks on result:
other: figure is based on absorbed and not applied dose
Mortality:
Animals generally died between 24 and 48hrs after application and no later than 4 days. The numbers and sexes of animals that died and the doses at which deaths occurred were not listed.
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Other findings:
- Potential target organs: Red blood cells, kidney
- Other observations: Hemoglobinuria and/or hematuria, and decreases in red blood cells and blood hemoglobin were observed in treated animals. In some animals treated with the substance, red blood cells fell to less than 10E12/liter and hemoglobin to 480-650 mmol/liter blood (20-25% of normal). The lowest values were reached after 48 to 72 hours and returned to normal over 8-14 days in animals who survived treatment.  The numbers and sexes of animals exhibiting these hematological changes and dose levels at which they were observed were not listed.
- Histopathology: Necropsy of animals that died revealed bloody kidneys and the presence of high quantities of blood in the bladder.  Closer examination of the bladders of these animals revealed a necrotizing, hemorrhagic, and atrophic acute tubular necrosis with occasional glomerular lesions, characterised by atrophic tubular dilation, tubular fatty degeneration, vacuolar degeneration, haematic pigment deposits in the glomerulus and the butubular cells with glumerular retraction and luminar hyaline deposits, luminar granular deposits, foci of cellular lysis, occasional interstitial fibro-inflammatory organisation and parietal atrophy.  Kidneys of animals who survived the 2-week observation period appeared normal. According to the authors, all the lesions observed were likely secondary effects following haemolysis.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on an LD50 of 1500mg/kg, a classification of harmful is appropriate. It should be borne in mind that this was absorbed and not applied dose.
Executive summary:

In an acute dermal toxicity study in rabbits where basic details were reported, an LD50 of 1500mg/kg was reported. The absorbed dose over the 24hr exposure period (between 610 -2200mg/kg), from which the results were calculated, represented only 8 -13% of the actual applied dose. All exposed animals showed marked haemoglobinuria.

Synopsis

LD50 (dermal) ~1500mg/kg