Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
according to general accepted protocols.
GLP compliance:
not specified
Test type:
other: not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
molecular weight: 117

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 215 - 295 g for males and 160-220 g for females
- Housing: stainless-steel cages
- Diet (e.g. ad libitum): ad libitum (standard lab chow, Purina)
- Water (e.g. ad libitum): not specified


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 71 ± 3°F
- Humidity (%): 50 ± 10% RH
- Photoperiod (hrs dark / hrs light): 12h light/dark cycle

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass chamber
- Exposure chamber volume: 54 litre
- Method of holding animals in test chamber: individual
- System of generating particulates/aerosols: vaporization of the liquid on a glass bead column. The total chamber airflow passed through the column and diluted the nitrite to the desired concentration. The nitrite flow to the bead column was controlled by a Sage syringe pumplModel 355).

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Exposure atmospheres were continuously monitored by an infrared spectrophotometer (Miran IA gas analyzer) and the output was displayed on a stripchart recorder (Linear, Model 156). The air was calibrated by serial injections of the liquid (i-PN) into a closed-loop system.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
not specified
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 14 days after exposure
- Necropsy of survicors: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight, necropsy
Statistics:
The calculation of the LC50 for the combined sexes, together with the slope and 95% confidence limits were based on the method of Finney (1964).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
716 ppm
Based on:
test mat.
95% CL:
>= 702 - <= 731
Exp. duration:
4 h
Remarks on result:
other: Slope 47
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.426 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: calculated
Mortality:
yes
Clinical signs:
irregular respiration
Remarks:
cyanosis
Body weight:
There were no significant effects of exposure on body weight gain during the 14-day postexposure observation period.
Gross pathology:
Necropsy examination of animals which died during the study indicated that signs of pulmonary hemorrhage were the only exposure-related macroscopic observation. At the terminal necropsy, after the postexposure observation period, there were indications of mild pulmonary hemorrhage (petechiae) found in less than half the animals.
Other findings:
During the exposure, the animals initially showed increased activity and blanching of the ears and feet, then gradually became cyanotic, and developed respiratory difficulties. In cases where death ensued, prostration, and, rarely, convulsions were observed after the initial signs. There were no significant differences in mortality between males and females.
In no instance did an animal die after cessation of an exposure. Animals that survived the 4 hr of exposure generally showed a marked improvement in behavior and appearance within 10-20 min of the exposure termination, even if they appeared close to death (i.e., severe respiratory difficulties, prostration) at the end of exposure. The signs of cyanosis, bluish ears and feet, persisted for up to several hours after the exposure. There were no significant effects of exposure on body weight gain during the 14-day postexposure observation period.

Any other information on results incl. tables

The LC50 ppm has been converted to mg/L with the following equation:

C (ppm) = mol. volume (24.45) /mol weight * C (mg/m³)

716 ppm = 24.45/117 * C (mg/m³)

C (mg/m³) = 3426 mg/m³ = 3.426 mg/L

(source: https://www.ccohs.ca/oshanswers/chemicals/convert.html)

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 based on EU GHS criteria
Remarks:
according to EU harmonised classification
Conclusions:
The LC50 (4h) in the rat for the test item was determined to be 716 ppm (3.426 mg/L). Impacts resulting from the corrosiveness of the substance cannot be excluded.
Executive summary:

The acute inhalative toxicity for the test item in the rat was investigated in an acute toxicity inhalation test (published by Klonne et al.) according to international standard protocols. 5 female rats and 5 male rats were exposed to a vapour of the test item in an 54 -litre glass chamber for 4 hours. Exposure atmospheres for the test item was generated by vaporization of the liquid on a glass bead column.

The 4-hr inhalation LC50 was determined for methyl-, ethyl-, n-propyl-, n-butyl-, isobutyl-, and isopentyl nitrite in Sprague-Dawiey rats. LC50 values were 176, 160, 300, 420, 777, and 716 ppm, respectively. The dose-mortality curves were characterized by extremely steep slopes. Toxic signs observed during exposure included cyanosis, prostration, and rarely, convulsions. There were no effects of exposure on body weight gain during a 14-day postexposure observation period. Signs of pulmonary hemorrhage were apparent in rats which died during exposure but were much less prominent in rats sacrificed at study termination. No animals died after cessation of exposure, and rapid recovery was apparent after exposure. Concentration X Time (CT) relationships suggested that the actual concentration was more important than the "dose" in determining the lethal effects of inhalation exposure to nitrites. Because of the extremely steep dose-mortality curves, the aliphatic nitrites are more hazardous than the LC50 values would indicate. The LC50 (4h) in the rat for the test item was determined to be 716 ppm (3.426 mg/L). Impacts resulting from the corrosiveness of the substance cannot be excluded.