Registration Dossier

Administrative data

Description of key information

The oral LC50 value for both males and females was 1478 mg/kg.  The acute dermal LD50 for nitromethane in rabbits was >2000 mg/kg.   The acute (4 hour) inhalation LC50 value is expected to be approximately 12 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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 The animals were given food and water ad libitum (with the exception that food was withdrawn the night before dosing).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
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.
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.
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.
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.

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),.


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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 478 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
circa 1940
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines and very limited information is available for interpretation of results. Study was also conducted with guinea pigs, species not typically used for acute inhalation toxicity studies.
Qualifier:
no guideline available
Principles of method if other than guideline:
Guinea pigs were exposed to various concentrations for various exposure periods. Animals were observed for at least 2 months following exposure and then necropsied.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
yes
Remarks on duration:
See below
Concentrations:
50,000 ppm for 1 hour
30,000 ppm for 0.25, 0.5, 1 or 2 hours
22,500 ppm for 1 hour
10,000 ppm for 1, 3 or 6 hours
5000 ppm for 3 or 6 hours
2500 ppm for 12 hours
1000 ppm for 30 or 48 hours
500 ppm for 140 hours

For longer exposures, report does not state how long animals were exposed each day or if it was a continuous exposure.
No. of animals per sex per dose:
Two guinea pigs per exposure
Control animals:
yes
Key result
Sex:
not specified
Dose descriptor:
LC100
Effect level:
50 000 ppm
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: 2 of 2 guinea pigs died
Key result
Sex:
not specified
Dose descriptor:
LC100
Effect level:
30 000 ppm
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: 2 of 2 guinea pigs died
Key result
Sex:
not specified
Dose descriptor:
LC100
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 2 of 2 guinea pigs died
Key result
Sex:
not specified
Dose descriptor:
other: approximate LC50
Effect level:
5 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 1 of 2 guinea pigs died therefore this is an approximate LC50
Key result
Sex:
not specified
Dose descriptor:
LC0
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: 0 of 2 guinea pigs died
Sex:
not specified
Dose descriptor:
LC0
Effect level:
500 ppm
Based on:
test mat.
Exp. duration:
140 h
Remarks on result:
other: 0 of 2 guinea pigs died

Symptoms of exposure included irritation, convulsant action, jerking or twitching movements of extremities, and slight, transient loss of weight. Stupor, narcosis, or light general anaesthesia was seen in exposures at >3% nitromethane in air. General visceral and cerebral congestion was present in all animals, including, to a lesser extent, the controls. Acute pulmonary congestion with oedema was noted in animals that died following high exposure concentrations. Animals also exhibited signs of upper respiratory irritation, as evidenced by the congestion. Liver damage of varying degrees was seen in all animals, regardless of route of administration. Gross changes in the kidneys, myocardium, and other organs and tissues consisted of oedema, pallor, or cloudy swelling and were like those usually seen following lethal doses of other materials.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
One of two guinea pigs exposed to 5000 ppm (~12 mg/L) for 6 hours died.
Executive summary:

The acute inhalation toxicity of nitromethane to guinea pigs was examined. The approximate LC50 was 5000 ppm following a 6 hour exposure. Stupor, narcosis, or light general anaesthesia was seen in exposures at 30,000 ppm nitromethane in air. General visceral and cerebral congestion was present in all animals, including, to a lesser extent, the controls. Acute pulmonary congestion with oedema was noted in animals that died following high exposure concentrations. Animals also exhibited signs of upper respiratory irritation, as evidenced by the congestion. Liver damage of varying degrees was seen in all animals, regardless of route of administration. Gross changes in the kidneys, myocardium, and other organs and tissues consisted of oedema, pallor, or cloudy swelling and were like those usually seen following lethal doses of other materials.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
circa 1940
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines and very limited information is available for interpretation of results. Study was also conducted with rabbits, species not typically used for acute inhalation toxicity studies.
Qualifier:
no guideline available
Principles of method if other than guideline:
Rabbits were exposed to various concentrations for various exposure periods. Animals were observed for at least 2 months following exposure and then necropsied.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
yes
Remarks on duration:
See below
Concentrations:
50,000 ppm for 1 hour
30,000 ppm for 0.25, 0.5, 1 or 2 hours
22,500 ppm for 1 hour
10,000 ppm for 1, 3 or 6 hours
5000 ppm for 3 or 6 hours
2500 ppm for 12 hours
1000 ppm for 30 hours
500 ppm for 140 hours


For longer exposures, report does not state how long animals were exposed each day or if it was a continuous exposure.
No. of animals per sex per dose:
Two rabbits per exposure
Control animals:
yes
Sex:
not specified
Dose descriptor:
LC100
Effect level:
50 000 ppm
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: 2 of 2 rabbits died
Sex:
not specified
Dose descriptor:
LC100
Effect level:
30 000 ppm
Based on:
test mat.
Exp. duration:
2 h
Remarks on result:
other: 2 of 2 rabbits died
Sex:
not specified
Dose descriptor:
LC100
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 2 of 2 rabbits died
Sex:
not specified
Dose descriptor:
other: approximate LC50
Effect level:
5 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 1 of 2 rabbits died therefore this is an approximate LC50
Sex:
not specified
Dose descriptor:
LC0
Effect level:
30 000 ppm
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: 0 of 2 rabbits died
Sex:
not specified
Dose descriptor:
LC0
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
3 h
Remarks on result:
other: 0 of 2 rabbits died

Symptoms of exposure included irritation, convulsant action, jerking or twitching movements of extremities, and slight, transient loss of weight. Stupor, narcosis, or light general anesthesia was seen in exposures at >3% nitromethane in air.

General visceral and cerebral congestion was present in all animals, including, to a lesser extent, the controls.
 Acute pulmonary congestion with edema was noted in animals that died following high exposure concentrations. Animals also exhibited signs of upper respiratory irritation, as evidenced by the congestion. Liver damage of varying degrees was seen in all animals, regardless of route of administration. Gross changes in the kidneys, myocardium, and other organs and tissues consisted cheifly of edema, pallor, or cloudy swelling and were like those usually seen following lethal doses of other materials.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
One of two rabbits exposed to 5000 ppm (~12 mg/L) for 6 hours died.
Executive summary:

The acute inhalation toxicity of nitromethane to rabbits was examined.

The approximate LC50 was 5000 ppm following a 6 hour exposure. Stupor, narcosis, or light general anesthesia was seen in exposures at 30,000 ppm nitromethane in air.

General visceral and cerebral congestion was present in all animals, including, to a lesser extent, the controls. Acute pulmonary congestion with edema was noted in animals that died following high exposure concentrations. Animals also exhibited signs of upper respiratory irritation, as evidenced by the congestion. Liver damage of varying degrees was seen in all animals, regardless of route of administration. Gross changes in the kidneys, myocardium, and other organs and tissues consisted cheifly of edema, pallor, or cloudy swelling and were like those usually seen following lethal doses of other materials.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
circa 1956
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
A group of 10 rats were exposed to 12.75 mg/L for one hour and observed for at least 48 hours following exposure.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No additional information available.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Raw air from a pressure line is passed to an expansion chamber. The air passes across the jet inlet of nitromethane from a continuous injection apparatus. The resulting vapor passes to a sealed exposure chamber containing the test animals.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
1 h
Concentrations:
12.75 mg/L
No. of animals per sex per dose:
10 rats
Control animals:
not specified
Details on study design:
Raw air from a pressure line is passed to an expansion chamber. The air passes across the jet inlet of nitromethane from a continuous injection apparatus. The resulting vapor passes to a sealed exposure chamber containing the test animals. Excess nitromethane, C02, and unused air are released from the top of the chamber. Analysls of the ingoing vapor to the chamber was by a colorimetric determination of a withdrawn sample.
Statistics:
No additional information available.
Preliminary study:
Not applicable.
Sex:
not specified
Dose descriptor:
LCLo
Effect level:
> 12.75 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
All animals survived the 1 hour exposure period and the 48 hour observation period.
Clinical signs:
There was "no appreciable sign of toxicity other than mild sedation and eye irritation" during exposure. Both of these effects resolved after rats were removed from the chamber.
Body weight:
No additional information available.
Gross pathology:
No additional information available.
Other findings:
No additional information available.

All animals lived for 48 hours after exposure. There was "no appreciable sign of toxicity other than mild sedation and eye irritation" during exposure. Both of these effects resolved after rats were removed from the chamber.

Conclusions:
The LClo is >12.75 mg/L following 1 hour exposure to nitromethane.
Executive summary:

The acute inhalation toxicity of nitromethane was examined. The LClo is >12.75 mg/L following 1 hour exposure to nitromethane.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
12 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 June 1980 - 14 July 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
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
test material was applied to abraded skin (one female tested with intact skin)
Principles of method if other than guideline:
Test material was applied to the skin for 24 hours under an impervious rubberized cloth. Animals were observed for 14 days following exposure.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
The animals were at least 9 weeks old and weighed at least 2 kg. They were acclimated for 7 days before use. Twenty four hours before the test, each animal was examined. Only animals with no skin injury were used. The animals were given food and tap water ad libitum.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test material (at 2000 mg/kg) was applied over a shaved area of abdominal skin and covered with a gauze patch and an impervious rubberized cloth. The dressings were removed after 24 hours.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
Probe study had one maile with abraded skin and and one female with intact skin.

Main study had 10 males and 5 females with abraded skin .
Control animals:
not specified
Details on study design:
A preliminary test was conducted with one male with abraded skin and one female with intact skin. The test material (at 2000 mg/kg) was applied over a shaved area of abdominal skin and covered with a gauze patch and an impervious rubberized cloth. The dressings were removed after 24 hours, and the animals were observed for toxicity over 14 days.

Since neither of the animals died, the study was repeated with 5 animals/sex, with abraded skin. The dressings were removed after 24 hours, and the sites of application were examined for erythema and edema. The animals were observed for toxicity over 14 days. Body weights were recorded prior to application of material and at 7 and 14 days. Complete necropsies were performed on animals that died. Gross necropsies were performed on all rabbits euthanized on day 14. Since one of the males died early on in the study, a second group of 5 males was added to the study.
Statistics:
If possible, LD50 value, slope and 95% confidence limits were calculated using the probit analysis of Finney (Cambridge Press, 1979) adapted to a BASIC computer program.
Preliminary study:
Both rabbits dermally exposed to nitromethane in the probe study survived.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the main study, one of five male and zero of five female rabbits dosed with 2000 mg/kg died. The only death occurred on day 4. The animal that died had evidence of a lung infection and discharge around the nose. Therefore a second group of five male rabbits were dosed with test material at the same dose; zero of five male rabbits died.
Clinical signs:
There was no evidence of dermal irritation noted in male or female rabbits. Discharge around the nose was observed in one male and one female.

Body weight:
Animals gained weight normally.
Gross pathology:
The animal that died had evidence of a lung infection.
Other findings:
None of the animals had evidence of skin irritation and the abrasions healed by 14 days.

No additional information available.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The dermal LD50 is >2000 mg/kg.
Executive summary:

The acute dermal LD50 for nitromethane in rabbits was examined.

One of 11 male rabbits and 0 of 6 female rabbits died following dermal exposure for 24 hours. The dermal LD50 is >2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

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 LD50 value (with the 95% confidence interval) for males was 1506 (1370-1602) mg/kg. The LD50 value (with the 95% confidence interval) for females was 1449 (1261-1560) mg/kg.  The LD50 value for both males and females was 1478 mg/kg. The study was not conducted according to guidelines but was conducted according to GLP and the report contains sufficient data for interpretation of study results

The acute dermal LD50 for nitromethane in rabbits was >2000 mg/kg. The study was not conducted according to guidelines, but was conducted according to GLP and the report contains sufficient data for interpretation of study results

 

In an acute inhalation study in rats, the LC50 is >12.75 mg/L following a one hour exposure to nitromethane. This study was conducted before guidelines and GLP, but sufficient data is available for interpretation of results. In another study a group of four rats were exposed to 2500 ppm (6.24 mg/L), for 6 hours/day for 4 consecutive days. The animals died after the 4th day. All 15 animals, exposed to 500 ppm (1.25 mg/L) for 6 hours/day for 3 weeks, survived until termination. In an acute inhalation toxicity with nitromethane in guinea pigs and rabbits, the approximate LC50 was 5000 ppm following a 6 hour exposure. All animals died after a 6 hour exposure to 10’000 ppm and after a one hour (guinea pigs) or 2 hour (rabbits) exposure to 30’000 ppm. Stupor, narcosis, or light general anaesthesia was seen in exposures at 30,000 ppm nitromethane in air.

Justification for classification or non-classification

Based on a weight of evidence approach using acute inhalation toxicity studies in rats, guinea pig and rabbit, the acute (4 hour) inhalation LC50 value is expected to be 12 mg/L (12’000 mg/m3 or ca. 5000 ppm). According to the CLP/GHS legislation, nitromethane can be classified as Category 4 for acute toxicity via the inhalation route. The substance does not need to be classified for acute toxicity via the oral and dermal route of exposure.