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Administrative data

Description of key information

The acute oral LD50 in rabbits was slightly lower than for rats, 625 and >/= 1000 mg/kg, respectively. The dermal LD50 was >2000 mg/kg in rabbits. The acute inhalation LC50 in rats is considered to be 6025 ppm.

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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:
1 Oct 1980 - 8 Sept 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to test guidelines and/or standard method and in accordance with GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Cox-SD
Sex:
male/female
Details on test animals and environmental conditions:
According to the protocol:Specie: RatStrain: Sprague-Dawley albino whiteSex: Equal numbers of male and femaleSource: Laboratory Supply, Indianapolis, INAge/Weight: At least 6 weeks/160-150 g (report states rats weighed 204 +/- 17 g)Identification: Individually numbered by body markingsHousing: Ten per cage. During the quarantine and after dosingQuarantine: At least 4 days.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% solution
Details on oral exposure:
Nitroethane (P-1355) was suspended in a 1% CMC solution and was administered by gavage in a single dose to Cox-SD albino rats weighing 204±17 g. The dosing solution was prepared on weight/volume basis. Ten male and ten female rats were used per dose level. The animals were fasted prior to dosing. The volume of the dosing solution was adjusted according to the dose and the body weight of the animal.
Doses:
The selected oral doses administered to the male and female rats were 0, 560, 800, 1100, 1600, and 2300 mg/kg. Additional dose levels of 950,1000, 1050, and 1250 mg/kg were administered to female rats only along with appropriate controls. For identification, the earlier dosed female rats were labelled as Group I and the later dosed female rats were labelled as Groups II (950), III (1000, 1050), and IV (950, 1050, 1250).
No. of animals per sex per dose:
Group I, 10 male and 10 female rats/dose. For groups II, III and IV, 10 female rats/dose.
Control animals:
yes
Details on study design:
All the animals in this study were observed frequently on the day of the compound administration and thereafter for 14 days. Any unusual signs of toxicity or death were noted during this period. The animals that died during the observation period were necropsied on the same day or the next day if the animal died during the night. At the end of 14 days, the surviving animals were weighed, sacrificed and examined for gross pathology.
Statistics:
The oral LD50' values, the 95% confidence limits (shown in parenthesis), and the slope (±SE) were calculated according to Finney (Probit Analysis, Cambridge University Press 1971) adapted to BASIC computer program.
Preliminary study:
Not applicable.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 428 mg/kg bw
Based on:
test mat.
95% CL:
1 232 - 1 657
Sex:
female
Dose descriptor:
LD50
Effect level:
1 083 mg/kg bw
Based on:
test mat.
95% CL:
991 - 1 167
Mortality:
See Table 1 below.
Clinical signs:
After oral dosing, the males at doses >800 mg/kg and the females at doses >1000 mg/kg were lethargic and ataxic by the fourth hour. The females showed anorexia, bloody nares at day 1, and hematuria and bloody feces by days 2 and 3. In both sexes the above conditions lasted from two to three days. The animals were normal by day seven.
Body weight:
See Table 1 below.
Gross pathology:
The necropsy of the animals found dead during the observation period showed severe intestinal hemorrhage.The necropsy of the surviving animals at day 14 showed that some of the male·and female rats, including the controls, showed lung infections. The other organs were grossly normal.
Other findings:
No additional information below.

Table 1 Acute Oral Toxicity of P-1355 in Rats

        Mortality  

 Dose

mg/kg

 Ave. Body Wt. Gain Dead/Treated  No/Day of Study

 Gross Pathological Observations*

     Male        
 0  50  0/10  --

 All organs normal

 560  40  0/10  --

 #8, 9 lung infection

 800  42  0/10  --

 #2 lung infection

 1100  43  0/10  --

 All organs normal

 1600  43  7/10  --

 #6 lung infection

 2300  --  10/10  --

 --

     Female        
 Group I      

 

 0

 23

 0/10

 --

 All organs normal

 560

13

 0/10

 --

 800

 16

 0/10

 --

 All organs normal

 1100

 18

 8/10

 1/1, 7/2

 All organs normal

 1600

 --

 10/10

 7/1, 3/2

 --

 2300

 --

 10/10

 4/1, 5/2, 1/3

 --

 Group II

 

 

 

 

 0

 7

 0/10

 --

 #2 lung infection

 950  5  0/10  --

 All organs normal

 Group III        
 0  15  0/10  --

 #10 lung infection

 1000  14  4/10  --

 All organs normal

 1050  8  6/10  1/1, 3/2, 1/3, 1/5

 All organs normal

 Group IV        
 0  23  0/10  --

 #2, 3, 4, 7, 8 lung infection

 950  21  0/10  --

 #1, 2, 4, 5 lung infection

 1050  16  0/10  --

 #1 lung infection

 1250  15  7/10  3/1, 1/2, 3/3

 All organs normal

*On surviving animals

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral.LD50 of nitroethane (P-1355) in male rats was 1428 (1232-1657) mg/kg and in the female rats was 1083 (991-1167) mg/kg.
Executive summary:

The acute oral toxicity of nitroethane was examined. The acute oral.LD50 of nitroethane (P-1355) in male rats was 1428 (1232-1657) mg/kg and in the female rats was 1083 (991-1167) mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 083 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
circa 1973
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
Principles of method if other than guideline:
Groups of rats were exposed for 6 or 7 hours to various concentrations of nitroethane for varying number of days. At 13,000 ppm (40.6 mg/L), rats were exposed for a single 6 or 7 hour period. At 2200 ppm rats (6.8 mg/L) were exposed for 6 hours for 5 exposures. At 200 and 550 ppm (0.625 and 1.55 mg/L, respectively), rats were exposed for 6 hours for 12 days.Rats were exposed to 200, 550, 2200 or 13,000 ppm nitroethane for six hours. At the lower concentrations, rats were exposed multiple days. Rats were exposed for 4 days to 2200 ppm and for three weeks to 200 or 550 ppm. Methemoglobin levels in the blood and test material concentration in liver, lung, heart and kidney were determined.
GLP compliance:
no
Test type:
other: rats were exposed for 6 or 7 hours for various number of exposures
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
not specified
Details on test animals and environmental conditions:
Wistar rats with a mean weight of 250 g were used. Animals were fed a diet devoid of nitrites.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Groups of 8-10 rats were exposed for 6-7 hours in inhalation chambers.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatographic analysis
Duration of exposure:
6 - 7 h
Concentrations:
13,000 ppm for 6 or 7 hours for a single exposure2200 ppm for 6 hours for 5 exposures550 ppm for 6 hours for 12 exposures200 ppm for 6 hours for 12 exposures
No. of animals per sex per dose:
8-10 rats/group
Control animals:
not specified
Details on study design:
Groups of 8-10 rats were exposed for 6-7 hours in inhalation chambers for a single - twelve exposures. After the last exposure, blood methemoglobin levels and NO2 levels in selected tissues were measured.
Statistics:
Mean levels of blood methemoglobin and NO2 levels in selected tissues were calculated.
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 19.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Rats survived repeated exposure to 2200 ppm (6.7 mg/L) for 6 hours/day for 5 days. The LC100 is 13'000 ppm following a six hour exposure to nitroethane.
Mortality:
See below.
Clinical signs:
See below.
Body weight:
See below.
Gross pathology:
See below.
Other findings:
See below

Experiment 1: Rats were exposed to 13,000 ppm nitroethane for several hours. The rats died 6 -7 hours during the inhalation exposure. The methemoglobin level of 2.8% was lower than that recorded for the nitropropanes, either 1 -NP or 2 -NP. Similarly with nitrite ion concentration. NE was found in the liver (0.8 mg) as well as in the lungs (0.1 ml).

Experiment 2: Animals placed in an atmosphere of 2200 ppm (6.8 mg/L) of nitroethane survived numerous 6-hour inhalation sessions. Nonmetabolized nitroethane in the liver was 0.1 mg/100 g. Since no noticeable effects were observed in rats exposed to 2200 ppm, groups of rats were exposed to lower concentrations for longer periods of time.

Experiment 3: Groups of rats were exposed to 550 ppm (1.55 mg/L) for 6 hours/day for 12 exposures. There was no methemoglobin noted in the blood and only traces of nitrites in the organs.

Experiment 4: Groups of rats were exposed to 200 ppm (0.625 mg/L) for 6 hours/day for 12 exposures. Similar to the results in experiment 3, there was no methemoglobin noted in the blood and only traces of nitrites in the organs.

Table 1 Effects following nitroethane exposure via inhalation

                  Level of NO2, ug/100 g tissue
 Exposure Conc., ppm  Number of exposures  Duration, hours  Methemoglobin, %  Heart  Lungs  Kidney  Spleen
 13,000  1  6 -7  2.84  930  192  255  700
 2,200  5  6  0  171  14  55  121
 550  12  6  0  236  60  trace  trace
 200  12  6  0  trace  trace  trace  trace
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LC50 of nitroethane is calculated to be 6025 ppm.
Executive summary:

The acute toxicity of nitroethane was examined following a single exposure to 13'000 ppm and repeated exposure to lower concentrations. Under the conditions of this study, the LC100 is 13'000 ppm following a six hour exposure to nitroethane.  All rats exposed to 2200 ppm of nitroethane for 6 hours/day for 5 days survived (LC0). This study was conducted before guidelines and GLP, but sufficient data is available for interpretation of results. Normalizing the LC0 value for a 4 hour exposure, this is equivalent to a LC50 of 6025 ppm/4 hr (2200*301/2/ 41/2). According to the CLP/GHS legislation, nitroethane can be classified as Category 4 for acute toxicity via the inhalation route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
19 882 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:
9 July 1980 - 20 Oct 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
According to the protocol:Strain : New Zealand ablino whiteSex: Equal number male and femaleSource: Kelley's. Rabbitry, Laconia , IndianaAge/Weight: At least 9 weeks/2 kgIdentification: Individually numbered on the inner side of the ear pinna,Housing: Individually caged during and after exposureQuarantine: At least 7 days
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test was conducted on ten rabbits (5 males and 5 females) weighing 2.7+/-0.2 kg. The animals' abdomens were shaved free of hair, and the skins in all the animals were further prepared by abrasions. The abrasions were made with a blunt hypodermic needle without obtaining bleeding and wereplaced 2-3 cm apart over the area of exposure, Each animal was treated with 2000 mg of liquid P-1355 per kg of body weight.For each rabbit, a weighed amount of P-1355 to give an appropriate dose per kg body weight, was spread over the prepared abdominal skin area. The skin area was then covered with a gauze and a sheet of impervious rubberized cloth to prevent any loss of the test material. The trunk was then further enclosed with a flexible stainless steel protective screen held in place by tape. The animals were then returned to their individual cages. After 24 hours of dermal exposure the bindings and patches were removed. The exposed areas were gently cleaned and observed for skin irritancy.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
Following removal of the wrap and cleaning the application site, the animals were returned to their individual cages and observed daily thereafter for another 14 days for any unusual signs of toxicity or death. At the end of 14 days, the surviving animals were weighed, sacrificed and examined for gross pathology.
Statistics:
According to the protocol, the dermal LD50 value, slope,. and 95% percentile confidence limits were estimated by the method of Finney (Probit Analysis. Cambridge Press 1979), adapted to BASIC computer program.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 24 hour exposure period and the 14 day observation period.
Clinical signs:
At the end of 24 hours of exposure, the treated skin sites in all the rabbits were normal..The animals showed no signs of toxicity or abnormal pharmacological behavior during the 14 day observation period.
Body weight:
The Mean and Standard Deviation for male rabbits was 2.602 +/- 0.176, 2.631 +/- 0.231 and 2.893 +/- 0.200 kg on study day 0, 7 and 14, respectively. The Mean and Standard Deviation for female rabbits was 2.859 +/- 0.136, 2.911 +/- 0.199 and 3.135 +/- 0.125 kg on study day 0, 7 and 14, respectively.
Gross pathology:
At necropsy, the treated skin sites were normal and a part of the treated skin site from each rabbit was excised and fixed in neutral formalin. The internal organs in all the rabbits were grossly normal.
Other findings:
No additional information available.

No additional information available.

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
All rabbits survived 24 hour exposure to 2000 mg/kg nitroethane as well as a 14 day observation period.
Executive summary:

The dermal toxicity of nitroethane was examined. All rabbits survived 24 hour exposure to 2000 mg/kg nitroethane as well as a 14 day observation period.

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

Additional information

The acute oral toxicity of nitroethane was examined in rats. In the most reliable study, the acute oral LD50 ranged from approximately 1428 mg/kg in male rats and 1083 mg/kg in female rats. In a dermal toxicity study of nitroethane all rabbits survived a 24 hour exposure to 2000 mg/kg nitroethane as well as a 14 day observation period. The acute toxicity of nitroethane to rats was examined following a single exposure to 13,000 ppm and repeated exposure to lower concentrations. Under the conditions of this study, the acute LC50 is considered to be 6025 ppm.

Justification for classification or non-classification

The acute oral LD50 from the key study is 1083 and 1428 mg/kg in female and male rats, respectively. Therefore, nitroethane is classified as category 4 under GHS. The acute inhalation LC50 is considered to be 6025 ppm (19'882 mg/m3) and, therefore, nitroethane is classified as category 4 under CLP/GHS. The dermal LD50 is greater than 2000 mg/kg and, therefore, nitroethane is not classifiable for acute dermal toxicity under CLP/GHS.