Ammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(10 animals/sex/dose)

Principles of method if other than guideline:

The study was conducted according to an internal BASF method whose principle is comparable to the OECD Guideline 401. A test group consisting of 10 animals/sex/dose was treated by single gavage with an aqueous solution of the test substance. Body weights were monitored during the 14 day observation period. The animals were observed for mortality and for clinical signs of toxicity for a period of 14 days. Decedents were subjected to necropsy. At the end of the observation period, the surviving animals were sacrificed (CO2 aphyxiation) for the purpose of necropsy. The LD50 value was estimated on the basis of the observed mortalities using the method of Finney D. J (Probit analysis, Cambridge University Press, 3 Aufl., 1971).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium chloride

EC Number:

235-186-4

EC Name:

Ammonium chloride

Cas Number:

12125-02-9

Molecular formula:

ClH4N

IUPAC Name:

ammonium chloride

Specific details on test material used for the study:

- Physical state: solid
- Analytical purity: 99.7%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr.K.THOMAE GmbH, Biberach, Germany
- Weight at study initiation: male: 170-178 g, female: 171-187 g (within 20% of mean weight)
- Fasting period before study: The animals were given no feed for 16 hours before administration, but water was available ad libitum
- Housing: 5 animals per cage (Type VII A steel cages; FA Becker & Co., Castrop-Rauxel)
- Diet: Kliba-Labordiaet, (Klingentalmuehle AG, CH); ad libitum
- Water: tap water; ad libitum
- Acclimation period: for at least one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Concentration of test substance in vehicle: 6.81, 10, 14.7, 21.5 %
- Maximum Volume applied: 10 mL/kg bw

Doses:

681, 1000, 1470, 1780, 2150 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of administration, at least once each workday. Check for mortality and moribund animals was performed twice daily on week days and once daily on Saturday, Sunday or on public holidays.
- Frequency of weighing: days 0, 3, 4, 7, 9, 13
- Necropsy of survivors performed: yes; before sacrifice, animals were fasted for a period of 16 hours
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 410 mg/kg bw

Based on:

dissolved

Remarks:

in water

95% CL:

>= 1 260 - <= 1 550

Remarks on result:

other: Slope factor = 1.36

Mortality:

Mortality: (out of 10 males and 10 females)
- Number of dead males at doses 2150, 1780, 1470, 1000 and 681: (after 1h) 8/7/4/0/0, (after 1d) 8/7/4/0/0, (≥2-14d) 8/7/4/0/0
- Number of dead females at doses, 2150, 1780, 1470, 1000, 681: (after 1h) 10/9/7/0/0, (after 1d) 10/9/7/3/0, (≥2-14d) 10/9/7/3/0

Clinical signs:

other: No clinical signs were manifested by animals of the lowest dose group (NOEL clinical signs = 681 mg/kg bw). Clinical signs were seen in animals dosed with 1000 mg/kg bw and above. Clinical symptoms indicated an influence on the central nervous system. Fo

Gross pathology:

Dying animals:
- General congestion: poor
- Heart: dilatation bilaterally; sporadically dilatation on the left side;
- Stomach: atonic; liquid contents; malacia of the mucosa in the glandular stomach;
- Intestines: atonic, diarrheal and mucous contents; malacia of the mucosa in several cases;

Other findings:

Histopathology (only one animal):
- Liver: fatty degeneration
- Kidney: fatty degeneration, lower nephron nephrosis

Any other information on results incl. tables

Table 1: Mortality

Dose (mg/kg bw)	Conc.	Gender	1 h	24 h	48 h	day 7	day 14
2150	21.5	male	8	8	8	8	8
		female	10	10	10	10	10
1780	17.8	male	7	7	7	7	7
		female	9	9	9	9	9
1470	14.7	male	4	4	4	4	4
		female	7	7	7	7	7
1000	10.0	male	0	0	0	0	0
		female	0	3	3	3	3
681	6.81	male	0	0	0	0	0
		female	0	0	0	0	0

Table 2: Weight (g)

Dose (mg/kg bw)	Gender	day 0	day 3/4	day 7	day 9	day 13
2150	male	178	216	248	262	-
	female	178	-	-	-	-
1780	male	171	206	236	245	-
	female	179	198	210	219	-
1470	male	170	210	241	251	-
	female	179	204	220	221	-
1000	male	177	226	246	-	283
	female	179	207	213	-	226
681	male	170	221	240	-	269
	female	171	205	210	-	218

Table 3: Clinical signs

Dose (mg/kg bw)	2150		1780		1470		1000		681
	male	female	male	female	male	female	male	female	male	female
Dyspnea	<15 m-5 h	<15 m-30 m	<15 m-5 h	<15 m-5 h	<15 m-5 h	<15 m-5 h	15 m-2 h	15 m-2 h	-	-
Apathy	<15 m-1 h	<15 m-30 m	<15 m-1 h	<15 m-1 h	<15 m-1 h	<15 m-1 h	30 m-2 h	30 m-2 h	-	-
Abnormal position	<15 m-1 h	<15 m-30 m	15 m-30 m	15 m-1 h	30 m	15 m-30 m	-	30 m	-	-
Stagger	1 h-5 h	-	<15 m-5 h	<15 m-5 h	<15 m-5 h	<15m-5 h	15 m-2 h	15 m-2 h	-	-
Atony	<15 m-30 m	<15 m-30 m	15 m-30 m	15 m-1 h	30 m	30 m	-	-	-	-
Twitching	<15 m-1 h	<15 m-30 m	15 m-1 h	15 m-1 h	30 m-1 h	15 m-1 h	-	30 m	-	-
Tonic convulsions	15 m-30 m	15 m-30 m	-	30 m	-	-	-	-	-	-
Piloerection	4 h-5 h	-	4 h-5 h	4 h-5 h	4 h-5 h	4 h-5 h	-	-	-	-
Exophthalmus	<15 m-1 h	<15 m-30 m	15 m-1 h	15 m-1 h	30 m-1 h	15 m-1 h	-	-	-	-
Poor general state	<15 m-1 h	<15 m-30 m	<15 m-1 h	<15 m-1 h	<15 m-1 h	<15 m-1 h	30 m-2 h	30 m-2 h	-	-

m: minutes

h: hour

d: day

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria