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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:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted according to generally accepted testing guidelines of the time. Basic data presented only.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Principles of method if other than guideline:
The study was conducted according to generally recognized procedures of the time. Equivalent to current methods.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance name: ethylene glycol monopropyl ether
Specific gravity: 0.913
Purity: >99.1%

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
Male New Zealand white rabbits were purchased from Dutchland Laboratory Animals, Inc., Denver, Pa. Water was available ad libitum. Food was available ad libitum and was Purina Laboratory Rabbit Chow. Rabbits were quarantined and acclimated to the laboratory conditions for at least three (3) weeks prior to treatments.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Back skin was closely clipped, but was not abraded. Depending on the volume administered, one or more pads were placed over the site. The pads were held in close contact with the skin by an occlusive wrap of dental dam. Test material was injected into the pad under the wrap using a long stainless steel intubation needle. The edges of the dental dam were sealed using adhesive tape. The wrap was removed after 24 hours, and the amount of residual material remaining was estimated and removed.
Duration of exposure:
14 day observation period
Doses:
Doses administered were 5.2, 10.5, 21.0 or 42.0 mmol/kg (541, 1092, 2184 or 4368 mg/kg, respectively).
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
All animals were observed twice daily for mortality and once a day for abnormal signs. Dermal responses were scored on Days 1, 3, 7, 10 and 14 (using the method of Draize). Individual body weights were recorded prior to dosing, on Day 7, and at death or termination (day 14). Survivors were killed on Day 14. All animals (including those that died) were autopsied. Gross pathology was recorded for all rabbits.
Statistics:
The LD50 value and confidence interval were calculated using the method of Thompson and Weil.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1 337 mL/kg bw
Based on:
test mat.
95% CL:
1 009 - 1 768
Remarks on result:
other: LD50: 12.86 (9.7-17.0) mM
Mortality:
Information not available
Clinical signs:
Anorexia, slight depression, cyanosis, ataxia and soft feces were seen at lower doses and salivation, nasal discharge, iritis, significant depression, labored breathing and prostration were seen at higher doses (doses not stated).
Body weight:
Information not available
Gross pathology:
Two of the low dose animals exhibited abnormal pathology. One animal in the 541 mg/kg group had red spots on the surface of the thymus and another had poor differentiation of the cortex and medulla of the kidney. All animals in the other groups had abnormal pathology. Animals dosed with 1092 mg/kg had a discolored margin of the liver (N=1), enlarged kidney (N=3), dark red kidney (N=1), poor differentiation of the cortex and medulla of the kidney (N=4), dark red stomach (N=1), and red discoloration of the large and small intestine (N=1). These changes were observed in 4-5 animals treated with 2184 mg/kg. One animal treated with 2184 mg/kg had a pale liver, and another had an enlarged spleen. Red discoloration of the large and small intestines and kidney toxicity also were found in 3 animals treated with 4368 mg/kg.
Other findings:
Administration of 2184 mg/kg (the highest dose tested at which enough animals survived to make an evaluation) produced slight skin irritation.

Applicant's summary and conclusion

Conclusions:
The LD50 value (and its confidence interval) was 12.86 (9.7-17.0) mmoles/kg, or 1337 (1009-1768) mg/kg. The number of individual deaths at each dose was not stated. Anorexia, slight depression, cyanosis, ataxia and soft feces were seen at lower doses and salivation, nasal discharge, iritis, significant depression, labored breathing and prostration were seen at higher doses (doses not stated).