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Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Adequacy of study:
supporting study
Study period:
1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Experimental investigation, but study well documented, meeting generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Structure-acute toxicity relationship of aromatic hydrocarbons in mice.
Author:
Tanii, H.; Huang, J.; Hashimoto, K.
Year:
1995
Bibliographic source:
Toxicol. Lett. 76:27-31.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
This study was carried out to assess the effect of metabolism on acute toxicity of aromatic hydrocarbons. To achieve this mice were pretreated with carbon tetrachloride at a dose level which did not cause death but which was known to inactivate hepatic microsomal monooxygenases
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylbenzene
EC Number:
202-849-4
EC Name:
Ethylbenzene
Cas Number:
100-41-4
Molecular formula:
C8H10
IUPAC Name:
ethylbenzene
Details on test material:
- Name of test material (as cited in study report): Ethylbenzene.

The aromatic hydrocarbons evaluated in this structure -activity study were benzene, toluene, o, m and p-xylene, cumene, propyl and butyl benzene.

Test animals

Species:
mouse
Strain:
other: ddY mice
Sex:
male
Details on test animals or test system and environmental conditions:
No data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Olive oil
Details on exposure:
The intraperitoneal LD50 was determined in mice for benzene and a series of 8 alkyl benzenes including ethyl benzene. The mice received either olive oil alone or olive oil containing 20% CCl4 by intraperitoneal injection 24 hours prior to determination of the intraperitoneal LD50 of the test materials. Observation continued over the following week and the test animals were observed thrice daily.

Additionally the n-octanol/water partition coefficient was measured for all the test materials
Doses:
No data
No. of animals per sex per dose:
Groups of 4 mice were used at each of 4 dose levels.
Control animals:
not specified
Details on study design:
No data
Statistics:
The LD50 was calculated according to Weil, 1952. The structure activity relationship was analysed by the model of Hansch and Fujita using log P.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
17.81 other: mmol/kg
Based on:
test mat.
Remarks on result:
other: IP LD50 CCl4-pretreated = 17.81 mmol/kg (17.81 df = 0)
Mortality:
No data
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
IP LD50 control = 19.7 mmol/kg (range 16.09-24.14)
IP LD50 CCl4-pretreated = 17.81 mmol/kg (17.81 df = 0)
(attributed to reduced metabolism due to carbon tetrachloride poisoning)

The authors calculated the to demonstrate the effect of metabolism on acute toxicity. A ratio of <1 implies a substance becomes more toxic after metabolism. Correlation with log P revealed a rough relationship between toxicity following metabolic saturation and increasing hydrophobicity.

Results for ethyl benzene are presented together with those at each end of the spectrum of values obtained. This study showed a significant correlation between acute toxicity and hydrophobicity.

benzene LD50 cont/LD50 CCl4 = 1.35; log P = 2.24
ethyl benzene LD50 cont/LD50 CCl4 = 1.11; log P = 3.34
butyl benzene LD50 cont/LD50 CCl4 = 0.53; log P = 4.34
Executive summary:

This study was carried out to assess the effect of metabolism on acute toxicity of aromatic hydrocarbons. To achieve this mice were pretreated with carbon tetrachloride at a dose level which did not cause death but which was known to inactivate hepatic microsomal monooxygenases.

The intraperitoneal LD50 was determined in mice for benzene and a series of 8 alkyl benzenes including ethyl benzene. The mice received either olive oil alone or olive oil containing 20% CCl4 by intraperitoneal injection 24 hours prior to determination of the intraperitoneal LD50 of the test materials. Observation continued over the following week and the test animals were observed thrice daily. Groups of 4 mice were used at each of 4 dose levels. The LD50 was calculated according to Weil, 1952.

Additionally the n-octanol/water partition coefficient was measured for all the test materials.

The structure activity relationship was analysed by the model of Hansch and Fujita using log P.

IP LD50 control = 19.7 mmol/kg (range 16.09-24.14)
IP LD50 CCl4-pretreated = 17.81 mmol/kg (17.81 df = 0)
(attributed to reduced metabolism due to carbon tetrachloride poisoning)

The authors calculated to demonstrate the effect of metabolism on acute toxicity. A ratio of <1 implies a substance becomes more toxic after metabolism. Correlation with log P revealed a rough relationship between toxicity following metabolic saturation and increasing hydrophobicity.

Results for ethyl benzene are presented together with those at each end of the spectrum of values obtained. This study showed a significant correlation between acute toxicity and hydrophobicity.

benzene LD50 cont/LD50 CCl4 = 1.35; log P = 2.24
ethyl benzene LD50 cont/LD50 CCl4 = 1.11; log P = 3.34
butyl benzene LD50 cont/LD50 CCl4 = 0.53; log P = 4.34

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