Nitrogen trifluoride

Endpoint summary

Description of key information

As NF₃is a gas the oral and dermal route of exposure are not considered relevant.

Of the numerous inhalation experiments conducted with NF₃only one experiment meets the requirements of REACh (Deichmann & Gerade) of a 4 hour exposure. The LC₅₀value reported here was 2000 ppm (equivalent to 5920 mg/m³) in mice; however details regarding the design of this study are lacking, with only an LC₅₀value reported. 

In the Vernotet al(1973) study, the inhalatory toxicity of NF₃was determined in a number of species including the rat and mouse. The design for this consisted of a single 1 hour exposure to rats and mice exposed whole body. The 1 hour LC₅₀values reported in this study were 6700 ppm (2264 mg/m³) and 7500 ppm 2534 mg/m³) for rats and mice, respectively. The rat value has been directly cited by the ISO 10298 International standards document for the determination of a gas or gas mixture. The inclusion of the mouse value here is compare the value obtained with the rat and the Deichmann & Gerade study. 

The data reported by Vernot et alconfirms that there is little in difference in terms of the acute toxicity of NF₃to mice or rats following a 1 h, whole-body exposure.

Following time adjustment using Haber’s rule to a 4h LC₅₀a value of 3350 ppm was derived for the rat (and 3750 ppm for the mouse). It is noted (by ISO 10298) that the use of Haber’s rule predicts a lower LC₅₀value when extrapolating from 1h to a 4h LC₅₀value. When comparing time adjusted 4h LC₅₀valuevs.experimentally generated data for the mouse, the time adjusted value is almost 2-fold greater. However, as originally stated however, the data reported by Deichmann & Gerade is not open to scientific scrutiny as no experimental details have been found in the published literature. It is therefore deemed appropriate to use the time adjusted LC₅₀value, which is viewed as a more conservative estimate of the toxicity. Furthermore, the rat LC₅₀value provides further assurance as it is the lower of the two time adjusted values.

Justification for selection of acute toxicity – oral endpoint

As nitrogen trifluoride is a gas, the oral route of exposure is not relevant

Justification for selection of acute toxicity – inhalation endpoint

The only available data in the literature which complies with requirements of REACh

Justification for selection of acute toxicity – dermal endpoint

As nitrogen trifluoride is a gas, the dermal route of exposure is not relevant

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a study on acute toxicity by the inhalation route is available

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

n/a

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP and non-guideline compliant

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study involved exposing several species of animal in NF3 for various times in order to determine LC50 values for 15, 30 and 60 mins

GLP compliance:

no

Test type:

fixed concentration procedure

Limit test:

no

Species:

other: rat ,mice, monkey, dog

Strain:

other: SD, ICR, rhesus, beagle

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Male SD and ICR mice were exposed (whole body) in a 30L bell jar chamber (10/gp of the same species). NF3 was introduced into the air stream prior to entry into a duplicate chamber which was used to establish contaminant concentrations. Air flow was fixed at 30 L/minute.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 15 - ca. 60 min

Concentrations:

Refer to results section

No. of animals per sex per dose:

10/gp

Control animals:

no

Details on study design:

Animals surviving the exposure were held up to 2 weeks to include delayed deaths. 

Statistics:

LC50 calculations were made by computerised version of the probit method of Finney.

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 6 700 ppm

95% CL:

ca. 6 130 - ca. 7 320

Exp. duration:

60 min

Remarks on result:

other: rat

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 3 350 ppm

Based on:

other: time adjusted

Exp. duration:

4 h

Remarks on result:

other: rat

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 7 500 ppm

95% CL:

ca. 6 800 - ca. 8 280

Exp. duration:

60 min

Remarks on result:

other: mouse

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 3 700 ppm

Based on:

other: time adjusted

Exp. duration:

4 h

Remarks on result:

other: mouse

Table 7.2.2/01-1: Mortality in rats and mice exposed to NF3 for 60 minutes

Concentration (ppm)		Mortality
Mean	Range
RAT
4118	4018 – 4428	0/10
5117	5002 – 5298	1/10
6121	5986 – 6232	4/10
7190	7134 – 7257	5/10
8204	8036 – 8282	9/10
LC50: 6700 ppm (6130 – 7320)
MOUSE
4112	3854 - 4264	0/10
6469	6297 – 6560	3/10
7150	6888 – 7544	4/10
8200	8150 – 8250	6/10
12218	12136 – 12300	10/10
LC50: 7500 ppm (6800 – 8280)

 

Interpretation of results:

Category 4 based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

9 916 mg/m³ air

Quality of whole database:

The study is not GLP compliant. From the 1h LC50 value determined in this study, the value has been time adjusted using Haber's rule to extrapolate to a 4h exposure

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because inhalation of the substance is likely

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

n/a

Justification for classification or non-classification

Acute oral toxicity:waiver requested as NF3 is a gas the oral route of exposure is not relevant.

 

Acute toxicity inhalation:The test material should be classified as ‘Acute Tox 4’ and the hazard statement ‘H332: Harmful if inhaled' should be applied according to the harmonised classification in Regulation 1272/2008.

   

Acute toxicity dermal:waiver requested as NF3 is a gas the dermal route of exposure is not relevant