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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 September 1980 - 15 October 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guidelines but was conducted according to GLPs and the report contains sufficient data for interpretation of study results

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Animals: The animals were at least 6 weeks old and weighed 200 +\- 25 g. They were acclimated for at least 4 days before use. The animals were given food and water ad libitum (with the exception that food was withdrawn the night before dosing). The animals were randomly allocated to groups of 10/sex.

Test material: The test material was suspended in 1% carboxymethyl cellulose.

Test conduct: The test material was administered by gavage at doses of 0, 600, 800, 1000, 1400 and 1800 mg/kg to groups of 10 animals per sex. The maximum dosing volume did not exceed 5 ml per animal. The animals were observed at least daily for 14 days. Animals were weighed before dosing and on days 7 and 14. Animals that died during the study and those that were terminated on day 14 were necropsied.

An additional study was performed with 2 groups of 10 animals/sex dosed with 0 or 1600 mg/kg to further refine the LD50 value, since all the animals exposed to 1800 mg/kg died.

Based on the mortality rate at the different dose levels, the oral LD50 value, 95% confidence limits, slope and standard error were calculated according to the method of Finney (probit analysis, Cambridge Press, 1979) adapted to a BASIC computer program.

Probe study: Prior to the definitive study a probe study was conducted. In the probe study, doses of 500, 1000, 1500 and 2000 mg/kg were administered to groups of 5 rats. The animals were observed for at least 7 days following oral dosing.
GLP compliance:
yes
Test type:
other: Oral LD50
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Nitromethane, % by wt. 95.88%
Nitroethane, % by wt. 3.31%
2-nitropropane, % wt. 0.55%
Water, % by wt. 0.023%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The male and female rats weighed approximately 200 and 190 g, respectively at the time of dosing. Rats were quarantined for a minimum of 4 days.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% carboxymethyl cellulose
Details on oral exposure:
The test material was administered by gavage at doses of 0, 600, 800, 1000, 1400 and 1800 mg/kg to groups of 10 animals per sex. The maximum dosing volume did not exceed 5 ml per animal.
Doses:
0, 600, 800, 1000, 1400, 1600 and 1800 mg/kg
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
The selected animals were fasted overnight. The fasted animals were gavaged with a selected dose. Each animal in the group was identified by a number. The animals were fed Purina Certified Rodent Chow 5002, ad libium. Each utilized lot was identified and dated. The diet was certified free of contaminants and the analysis was performed by the supplier. Tap water was supplied ad libium. Every quarter the animals drinking water was analyzed to ensure that the levels of contaminants were equal to or less than the recommended levels as per the Primary Drinking Water Regulations (40CFR 141.11, 141.12, 141.14).

The animals were observed at least daily for 14 days. Animals were weighed before dosing and on days 7 and 14. Animals that died during the study and those that were terminated on day 14 were necropsied. All major organs and the body caviies were examined for gross abnormalities and gthe the carcasses were discarded. Any unusual observation will be recorded and reported.
Statistics:
Based on the mortality rate at the different dose levels, the oral LD50 value, 95% confidence limits, slope and standard error were calculated according to the method of Finney (probit analysis, Cambridge Press, 1979) adapted to a BASIC computer program.

Results and discussion

Preliminary study:
In a probe study, doses of 500, 1000, 1500 and 2000 mg/kg were administered to groups of 5 rats. No mortality was noted at 500 mg/kg after 7 days. Two of five and three of five died within 7 days following administration of 1000 and 1500 mg/kg, respectively. All rats died within 24 hours following administration of 2000 mg/kg. Rats in the 2000 mg/kg group were observed to be very nervous and shaky 3 hours after dosing.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 506 mg/kg bw
95% CL:
> 1 370 - < 1 602
Sex:
female
Dose descriptor:
LD50
Effect level:
1 499 mg/kg bw
95% CL:
> 1 261 - < 1 560
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 478 mg/kg bw
Mortality:
Female mortality
600 mg/kg - 0 of 10
800 mg/kg - 0 of 10
1000 mg/kg - 0 of 10
1400 mg/kg - 5 of 10 (4 died on day 1 and 1 died on day 3)
1600 mg/kg - 6 of 10 (7 died on day 1 and 1 died on day 4)
1800 mg/kg - 10 of 10 (10 died on day 1)

Male mortality
600 mg/kg - 0 of 10
800 mg/kg - 0 of 10
1000 mg/kg - 0 of 10
1400 mg/kg - 3 of 10 (3 died on day 1)
1600 mg/kg - 6 of 10 (6 died on day 1)
1800 mg/kg - 10 of 10 (9 died on day 1 and 1 died on day 3)
Clinical signs:
Males exposed to 1800 mg/kg were hyperactive at 7 hours, and females exposed to this dose exhibited a bloody discharge from the nose at 7 hours and convulsions at 13 hours. 

Animals treated with 1600 mg/kg exhibited tremors 2 and 4 hours after dosing.
Body weight:
First study: Average group weights of surviving males treated with any concentration of test material and surviving females treated with up to and including 1000 mg/kg were similar to controls.  Body weight gains of females treated with 1400 mg/kg were lower than control (7.1% gain vs. 14.6%) between days 0 and 7, but not between days 7 and 14.  

Second study: Body weight gains of males and females exposed to 1600 mg/kg were lower than control between days 0 and 7 (males 30.3 and 24.3% for control and 1600 mg/kg groups, respectively; females 16.4 and 6.2% gain for control and 1600 mg/kg groups, respectively), and higher than control between days 7 and 14 (males 14.6 and 22.8% for control and 1600 mg/kg groups, respectively; females 4.7 and 7.8% gain for control and 1600 mg/kg groups, respectively),.
Gross pathology:
First study: Necropsies of animals that died showed hemorrhage of intestines and/or lungs. With the exception of 4 animals with lung infections, gross necropsies of all other animals were normal.

Second study: The animals that died on the first day had hemorrhaged intestines at necropsy. The animal that died on day 4 died on the weekend and was not necropsied.  The 6 survivors had normal necropsies on day 14.
Other findings:
No additional information available.

Any other information on results incl. tables

First study: None of the controls or rats exposed to concentrations = 1000 mg/kg died.  Three males and four females exposed to 1400 mg/kg died on day 1, and an additional female exposed to 1400 mg/kg died on day 3. All animals exposed to 1800 mg/kg died (19/20 on day 1 and 1 male on day 3). Males exposed to 1800 mg/kg were hyperactive at 7 hours, and females exposed to this dose exhibited a bloody discharge from the nose at 7 hours and convulsions at 13 hours.  Necropsies of animals that died showed hemorrhage of intestines and/or lungs. With the exception of 4 animals with lung infections, gross necropsies of all other animals were normal.  Average group weights of surviving males treated with any concentration of test material and surviving females treated with up to and including 1000 mg/kg were similar to controls.  Body weight gains of females treated with 1400 mg/kg were lower than control (7.1% gain vs. 14.6%) between days 0 and 7, but not between days 7 and 14.   

Second study:
  None of the controls died.   Animals treated with 1600 mg/kg exhibited tremors 2 and 4 hours after dosing. Six out of 10 exposed males and 7/10 exposed females died on day 1. An additional female died on day 4. The animals that died on the first day had hemorrhaged intestines at necropsy. The animal that died on day 4 died on the weekend and was not necropsied.  The 6 survivors had normal behavior and necropsies on day 14. Body weight gains of males and females exposed to 1600 mg/kg were lower than control between days 0 and 7 (males 30.3 and 24.3% for control and 1600 mg/kg groups, respectively; females 16.4 and 6.2% gain for control and 1600 mg/kg groups, respectively), and higher than control between days 7 and 14 (males 14.6 and 22.8% for control and 1600 mg/kg groups, respectively; females 4.7 and 7.8% gain for control and 1600 mg/kg groups, respectively),.


Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LC50 value for both males and females was 1478 mg/kg.
Executive summary:

The acute oral toxicity of nitromethane was examined in rats. Groups of 10 male and 10 female rats were dosed with 0, 600, 800, 1000, 1400, 1600 and 1800 mg/kg and observed for 14 days.

All rats dosed with 1000 mg/kg survived the two week observation period. The LC50 value (with the 95% confidence interval) and slope of the line for males was 1506 (1370 - 1602) mg/kg and 21.7 +/- 6.9, respectively. The LC50 value (with the 95% confidence interval) and slope of the line for females was 1449 (1261 - 1560) mg/kg and 16.4 +/- 5.2, respectively. The LC50 value for both males and females was 1478 mg/kg.