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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Based upon a review of the available data the following effect level has been chosen for acute toxicity: inhalation:
LC50 (rat) at 60 mins for nitrogen dioxide: 115 ppm.
The modification of exposure duration to 4-hour exposure using Haber's law results in the 4-h LC50 for nitrogen dioxide of 28.8 ppm, or 55 mg/m3. Considering one mole dinitrogen tetraoxide results in the formation of two moles of nitrogen dioxide, this value was recalculated to 14.4 ppm by the registrant, which is equal to 55 mg/m3 , for dinitrogen tetraoxide.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
55 mg/m³ air
Quality of whole database:
The study has a Klimisch score 2.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Toxicity: Oral and dermal

The substance is a gas and is classified as corrosive to skin. Therefore in accordance with column 2 of Annex VII (required in section 8.5) of REACH Regulation 1907/2006 the study does not need to be conducted.

Acute Toxicity: Inhalation

The substance is classified as corrosive to skin. Therefore in accordance with column 2 of Annex VIII (required in section 8.5) of REACH Regulation 1907/2006 the study does not need to be conducted. However, there is some literature data available for the test material (Peng et al, 2004) and also nitrogen dioxide (Carson et al, 1962), which can be read across to the test material based upon the following justification:

It is understood that there is an equilibrium existing between NO2 and N2O4. Hence, it would seem inevitable that any toxicity studies conducted with these oxides will share common toxicities. It also seems plausible that the prevalent oxide of nitrogen would be nitrogen dioxide.

The results obtained from the available literature data is as follows:

Dinitrogen Tetroxide:

Peng et al (2004)

The first 2 - 6 h after intoxication is the most severe stage of the injury. During the long-term observation intoxication with the test material can induce pulmonary fibrosis and adenocarcinoma.

Nitrogen dioxide:

Carson et al (1962)

Rat: Based on the lung to body weight ratio and the pathological changes found in exposed animals, the LC50 concentrations of the test item were 416, 201 and 115 ppm for 5, 15 and 60 min, respectively.

Rabbit: Rabbits were exposed for 15 minutes to various concentrations of the test item. The LC50 was estimated to be 315 ppm.

Dog: Dogs were exposed for single 5- to 60-minute periods to various concentrations of the test item. Dogs had only mild toxic signs to exposure to the test item.

Based upon a review of this data the following effect level has been chosen as the literature paper provides LC50 values and the preferred species (rat) is used:

LC50 (rat) at 60 mins: 115 ppm

The modification of the exposure duration from 60 minutes to 4 hours using Haber's law, as recommended by the ECHA guidance on information requirements and chemical safety assessment (cn x t = const), where n = 1 for the extrapolation from shorter to longer exposure durations, results in 4 -h LC50 of 28.8 ppm, or 55 mg/m3. Considering one mole dinitrogen tetraoxide results in the formation of two moles of nitrogen dioxide, this value was recalculated to 14.4 ppm for dinitrogen tetraoxide by the registrant, which is equal to 55 mg/m3.


Justification for selection of acute toxicity – oral endpoint
The substance is a gas and is classified as corrosive to skin. Therefore in accordance with column 2 of Annex VII (required in section 8.5) of REACH Regulation 1907/2006 the study does not need to be conducted.

Justification for selection of acute toxicity – inhalation endpoint
The substance is classified as corrosive to skin. Therefore in accordance with column 2 of Annex VIII (required in section 8.5) of REACH Regulation 1907/2006 the study does not need to be conducted. However, there is some literature data available for the test material (Peng et al, 2004) and also nitrogen dioxide (Carson et al, 1962), which can be read across to the test material based upon the following justification:

It is understood that there is an equilibrium existing between NO2 and N2O4.Hence, it would seem inevitable that any toxicity studies conducted with these oxides will share common toxicities. It also seems plausible that the prevalent oxide of nitrogen would be Nitrogen Dioxide.

The results obtained from this literature data is as follows:

Dinitrogen Tetroxide:
Peng et al (2004)
The first 2 - 6 h after intoxication is the most severe stage of the injury. During the long-term observation, we find that intoxication with the test material can induce pulmonary fibrosis and adenocarcinoma.

Nitrogen dioxide:
Carson et al (1962)
Rat: Based on the lung to body weight ratio and the pathological changes found in exposed animals, the threshold concentrations of the test item found were 104, 65 and 28 ppm for 5, 15 and 60 min, respectively.

Rabbit: Rabbits were exposed for 15 minutes to various concentrations of the test item. The LC50 was estimated to be 315 ppm.

Dog: Dogs were exposed for single 5- to 60-minute periods to various concentrations of the test item. Dogs had only mild toxic signs to exposure to the test item.

Based upon a review of this data the following effect level has been chosen as the literature paper provides LD50 values and the preferred species (rat) is used:

LC50 (rat) at 60 mins: 115 ppm

The modification of the exposure duration using Haber's law, as recommended by the ECHA guidance on information requirements and chemical safety assessment, to 4-hour exposure results in 4-h LC50 of 28.8 ppm, or 55 mg/m3.

Justification for selection of acute toxicity – dermal endpoint
The substance is a gas and is classified as corrosive to skin. Therefore in accordance with column 2 of Annex VII (required in section 8.5) of REACH Regulation 1907/2006 the study does not need to be conducted.

Justification for classification or non-classification

The substance is currently classified as Acute Tox. 2* according to Annex VI of Regulation (EC) No 1727/2008, however the asterix against it indicates that it is a "de minimis" classification made by conversion of the entries of Annex I of the DSD with other classification criteria in mg/L.

In the study of Carsson et al. (1962), 1 -hour LC50 of 115 ppm was obtained. The modification of the exposure duration to 4 hours using Haber's law, as recommended by the ECHA guidance on information requirements and chemical safety assessment, results in the 4 -h LC50 of 28.8 ppm, or 55 mg/m3. Considering one mole dinitrogen tetraoxide results in the formation of two moles of nitrogen dioxide, this value was recalculated to 14.4 ppm by the registrant, which is equal to 55 mg/m3 , or 0.055 mg/L for dinitrogen tetraoxide. Therefore the classification of dinitrogen tetraoxide as Acute Tox. 1, H330 in accordance with Regulation 1272/2008/EC is proposed by the registrant.

The harmonized classification of dinitrogen tetraoxide according to Regulation 1272/2008/EC gives a specific concentration limit of 0.5% for classification with STOT SE 3, H335. However, respiratory tract irritation is inherent to the corrosive properties of the substance and is considered therefore to be covered by classification as Skin Corr. 1B, H314 and EUH071 (Corrosive to respiratory tract). Therefore a separate classification as STOT SE 1, H335 is considered to be not necessary.