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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
circa 1942
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results

Data source

Reference
Reference Type:
publication
Title:
The Metabolism of Nitroparaffins: II The Metabolic Products of Nitroethane
Author:
Scott, E.W.
Year:
1942
Bibliographic source:
Journal of Industrial Hygiene and Toxicology 24: 226-228

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
In vitro and in vivo metabolism of nitroethane was examined in rabbit blood.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test material was described as nitroethane. No information on source of material provided.

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
intravenous
Vehicle:
not specified
Duration and frequency of treatment / exposure:
A single intravenous dose of nitroethane was administered to a rabbit.;;
Doses / concentrations
Remarks:
Doses / Concentrations:982 mg nitroethane was administered.
No. of animals per sex per dose:
one
Control animals:
other: animal served as it's own control

Results and discussion

Preliminary studies:
Not applicable.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not applicable.
Details on distribution in tissues:
Not applicable.
Details on excretion:
Not applicable

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Acetaldehyde and nitrite were found in blood following intravenous administration.

Any other information on results incl. tables

In vitro study

In the in vitro study using H2O2, the distillate contained 77% of the original nitroethane and acetaldehyde in an amount equivalent to 16% of the nitroethane, leaving a loss of 7% in the recovery.

In the experiment without H2O2, 80% nitroethane and 18.5% of the nitroethane as acetaldehyde. No detectable acetaldehyde was observed in a sample of blood (no nitroethane added) treated in the same way.

In vivo study

Once 5% mercuric chloride followed by 1% sodium carbonate was used as a protein precipitant, the presence of increased nitrite after injections of nitroethane was then easily demonstrated. In the rabbit receiving 1.0 gram nitroethane intravenously, the values per 100 ml of blood for nitroethane and nitrite respectively were 58.5 and 0.60 mg after 30 minutes, 68.0 and 0.62 mg after 120 minutes and almost nil for both after 5 hours. The nitrite color of the 5 -hour sample, however, was definitely deeper than that shown for the blank. The proportion of nitrite found in comparison to the amount of nitroethane given and acetaldehyde previously found, was relatively low. This was probably due to the readiness with which oxyhemoglobin reacts with nitrite which is thus, for the most part, converted to nitrate.

In order to test this hypothesis, a rabbit was given 50 mg NaNO2 intravenously. The blood nitrite of this animal was 3.88 mg/100 ml after 5 minutes, 1.96 mg/100 ml after 45 minutes, 0.60 mg/100 after 120 minutes and 0.28 mg/100 ml after 240 minutes. The results indicate that the nitrite ion is rapidly removed from the blood until a certain level is reached, after which the decrease in concentration becomes more gradual.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study resultsFollowing intravenous administration of nitroethane, acetaldehyde and nitrite were found in relatively large amounts in rabbit blood.
Executive summary:

Following intravenous administration of nitroethane, acetaldehyde and nitrite were found in relatively large amounts in rabbit blood.