Ammonium hydrogendifluoride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18th October to 2nd November 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium hydrogendifluoride

EC Number:

215-676-4

EC Name:

Ammonium hydrogendifluoride

Cas Number:

1341-49-7

Molecular formula:

F2H5N

IUPAC Name:

ammonium fluoride hydrofluoride

Details on test material:

Ammoniumhydrogenfluoride (NH4FxHF), a white crystalline industrial compound. Batch number: 21-06-89.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley (SPF outbred) rats, aged 5-6 weeks on arrival, obtained from the Central Institute of Laboratory Animal Breeding, Hannover. Initial body weights for males were 146-28 g, and for females were 118-176 g. Rats were housed individually in stainless steel cages in quarantine at a temperature of 20-22°C and relative humidity of 50-60%, on a 12 hour light/dark cycle. There were approximately 15 air changes per hour. Food (Altromin Co. R1324 mixed food) and tap water were provided ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 2% Tylose

Details on oral exposure:

Ammoniumhydrogenfluoride was suspended in 2% Tylose (pH ranging fom 3.9 - 6.8). The substance was administered in a single dose via gastric tube. A fixed dosing volume of 10 ml/kg bw was used.

Doses:

0, 21.5, 46.4, 100 and 147 mg/kg bw.

No. of animals per sex per dose:

10 rats of each sex per dose.

Control animals:

yes

Details on study design:

The rats were randomised by help of a computer card. The rats were fasted approximately 16-20 hours before dosing. After administration of the single dose, rats were observed for 14 days. Behaviour, food consumption and body weight gain were recorded. At the end of the observation period all surviving animals were sacrificed, necropsied and examined macroscopically. Necropsy was performed immediately after death in rats that died during the observation period.

Statistics:

Body weight and food consumption data were evaluated using descriptive methods and ANOVA.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LDLo

Effect level:

100 mg/kg bw

Remarks on result:

other: 1 male out of 10 died

Effect levels 2

Sex:

female

Dose descriptor:

LDLo

Effect level:

147 mg/kg bw

Remarks on result:

other: 8/10 animals died

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

130 mg/kg bw

Remarks on result:

other: Estimated based on deaths occurring at dose levels of 100 and 147 mg/kg

Mortality:

Six males and 8 females in the high dose group (147 mg/kg bw) within 2 days of administration. One male in the 100 mg/kg bw group died 4.5 hours after administration.

Clinical signs:

other: Clinical signs were apparent at doses of 46.4 mg/kg bw and higher and included; dyspnoea, decreased spontaneous motility, sedation, decreased cutaneous circulation, piloerection, ataxia, decreased body tone, respiratory sounds and markedly diminised food

Gross pathology:

There were no abnormal findings in rats administered 0, 21.5 or 46.4 mg/kg bw.
1 male in the 100 mg/kg group exhibited a reddened thymus; stomach: gastric dilation, hyperaemia, edematous wall, single ulcera spread over the entire mucosa, suspicion of mucosa detachment, jejunum: single reddened areas, ileum: reddened.
At 147 mg/kg bw: 3 males and 3 females: stomach: gastric dilation, hyperaemia, edematous wall, single ulcera spread over the entire mucosa, suspicion of mucosa detachment. 1 male stomach had gastric mucosa without abnormal finding but some bloody content. 3 males and 3 females displayed bloody content and hyperaemic mucosa of the small intestine. 2 males and 3 females had hyperaemic mucosa in the caecum. 1 male had reddened peyer's patches. 2 males had reddened Nll. mesenteriales. 1 male exhibited grey kidneys, with a white-red coloured cortex, about 2-3 mm spongioid consistency.

Other findings:

No other findings reported.

Any other information on results incl. tables

Table 1. Toxicity symptoms and time of onset.

Dose group	Symptoms	Time of Onset
Controls	No abnormal findings	-
21.5 mg/kg	No abnormal findings	-
46.4 mg/kg	1 male and some females showed decreased spontaneous motility, the 1 male also showed dyspnoea.	Symptoms appeared within 15 minutes of administration, but disappeared 75 minutes after dosing.
100 mg/kg	Dyspnoea, respiratory sounds, piloerection, decreased cutaneous circulation, slight ataxia, half closed eyes, decreased spontaneous motility. Sedation was observed although the animals responded to disturbance. 1 male died after 4.5 hours	Symptoms appeared within 15 minutes of administration, but disappeared 4 days after dosing.
147 mg/kg	6/10 males and 8/10 females died within 2 days of administration. Severe dyspnoea, decreased cutaneous circulation, slight ataxia, decreased body tone, prone position, sedation, cyanosis, salivation, lacrimation, mydriasis, slight haemorrhagic discharge from the nose. After 24 hours all surviving rats showed bad general condition.	Symptoms appeared 10 minutes after dosing and remained until the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Ammoniumhydrogenfluoride was classified as Toxic if swallowed according to EC guideline 79/831, annex VI, part 1.

Executive summary:

The acute oral toxicity of ammonium hydrogenfluoride was determined according to OECD method 401. The test substance was administered to male and female Sprague-Dawley rats by gavage in single doses of 21.5, 46.4, 100 or 147 mg/kg bw. The control group received vehicle alone (2% Tylose). Dose-dependent symptoms occurred immediately after dosing and lasted less than 2 hours after treatment with 46.5 mg/kg bw, or up to 14 days after treatment with 147 mg/kg bw. Symptoms included dyspnoea, ataxia, reduced circulation and decreased spontaneous motility. One male rat (n = 10) died in the 100 mg/kg bw group, and 6 males (n = 10) and 8 females (n = 10) died in the 147 mg/kg bw group. Deaths occurred between 1 hour and 2 days following administration. The LD50 was therefore estimated to be 130 mg/kg bw.