Hexafluorosilicic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Range-finding study for the NTP carcinogenicity study.

Data source

Reference

Reference Type:

publication

Title:

Technical Report on the Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F1 Mice.

Author:

NTP

Year:

1990

Bibliographic source:

U.S Department of Health and Human Services. NTP TR 393, NIH Publication No. 91-2848

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: NTP protocol

Principles of method if other than guideline:

14-day dose range-finding study in the rat.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium fluoride

EC Number:

231-667-8

EC Name:

Sodium fluoride

Cas Number:

7681-49-4

Molecular formula:

FNa

IUPAC Name:

sodium fluoride

Details on test material:

Sodium fluoride (read-across)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female rats were obtained from Charles River Laboratories (Portage, MI) and were observed for 6 days. The rats were 5 weeks old when placed on the study. The rats were fed on a semisynthetic low fluoride diet, available ad libitum. Water was supplied in glass bottles with rubber stoppers and stainless steel sipper tubes that were changed every 3 days. The cages were kept at a temperature of 21-23 degC with a relavtive humidity of 40-60%. Fluorescent light was supplied for 12 hours per day.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

0, 50, 100, 200, 400 or 800 ppm sodium fluoride in deionised water, available ad libitum.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Nominal concentrations.

Duration of treatment / exposure:

The study was 14 days in length. The sodium fluoride was available ad libitum in the drinking water.

Frequency of treatment:

The sodium fluoride was available ad libitum in the drinking water.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm

Remarks:

nominal in water

Doses / concentrations 2

Dose / conc.:

50 ppm

Remarks:

nominal in water

Doses / concentrations 3

Dose / conc.:

100 ppm

Remarks:

nominal in water

Doses / concentrations 4

Dose / conc.:

200 ppm

Remarks:

nominal in water

Doses / concentrations 5

Dose / conc.:

400 ppm

Remarks:

nominal in water

Doses / concentrations 6

Dose / conc.:

800 ppm

Remarks:

nominal in water

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

Groups of five rats of each sex received 0, 50, 100, 200, 400 or 800 ppm sodium fluoride in deionised water ad libitum. Animals were housed five per cage with semisynthetic low fluoride feed available ad libitum. Water consumption was recorded every 3 days. The rats were observed twice daily for signs of morbidity, mortality and signs of toxicity. They were weighed at the beginning, at the end of the first week and at necropsy. All animals were necropsied and tissues examined for gross lesions. No further investigations were performed.

Positive control:

Not relevant

Examinations

Observations and examinations performed and frequency:

Water consumption was recorded every 3 days. The rats were observed twice daily for signs of morbidity, mortality and signs of toxicity. They were weighed at the beginning, at the end of the first week and at necropsy.

Sacrifice and pathology:

All animals were necropsied and tissues examined for gross lesions.

Other examinations:

No further examinations

Statistics:

Various

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

All male and female rats given water containing 800 ppm sodium fluoride died; 1/5 female given 400 ppm also died. No gross lesions were observed at necropsy. All groups of males and females surviving to the end of the studies gained weight except the group receiving 400 ppm. In this group, 4/5 male lost 5-31% of their initial body weight and 3/4 female lost 10-29% of their initial body weight.

The following signs of toxicity were noted in all animals in the two highest dose groups: dehydration and lethargy by day 4 and hunched posture by day 5. In addition, reduced water consumption recorded by cage for male and female in the second highest dose group (400 ppm).

Effect levels

1

Dose descriptor:

NOEL

Effect level:

200 ppm

Sex:

female

Basis for effect level:

other: Mortality, bodyweight effects, clinical signs, reduced water consumption

2

Dose descriptor:

NOEL

Effect level:

200 ppm

Sex:

male

Basis for effect level:

other: Bodyweight effects, clinical signs, reduced water consumption

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Dose (ppm)	Survival	Mean Body Weight			Final Weight relative to control (%)
		Initial	Final	Change
Male
Control	5/5	86 ±5	167 ±6	81 ±3	100
50	5/5	79 ±3	151 ±4	72 ±2	91
100	5/5	75 ±4	146 ±5*	71 ±1*	88
200	5/5	77 ±3	140 ±6**	62 ±4**	84
400	5/5	80 ±3	69 ±6**	-11 ±5**	41
800	0/5	79 ±2	-	-	-
Female
Control	5/5	80 ±4	133 ±2	53 ±3	100
50	5/5	74 ±3	128 ±3	53 ±4	96
100	5/5	79 ±4	128 ±2	49 ±2	96
200	5/5	77.0 ±5	128 ±4	51 ±3	96
400	4/5	80 ±4	79 ±14**	0 ±15**	59
800	0/5	77 ±3	-	-	-

*Significantly different (P≤0.05) from the control group by Dunn’s or Shirley’s test

**P<0.01

Applicant's summary and conclusion

Conclusions:

In the 14 day study, all male and female rats given water containing 800 ppm of sodium fluoride died. Effects at the second highest concentration (400 ppm) included weight loss, dehydration and lethargy. All other groups showed little signs of toxicity; males and females surviving to the end of the study gained weight.

Executive summary:

In the 14 day study, all male and female rats given water containing 800 ppm of sodium fluoride died; 1/5 female given 400 ppm died. No gross lesions were observed at necropsy. All groups, male and female, surviving to the end of the studies gained weight except the group receiving 400 ppm. In this group, 4/5 male lost form 5-31% of their initial body weight and 3/4 female lost from 10-29% of their initial body weight. The following signs of toxicity were noted in all animals in the two highest dose groups: dehydration and lethargy by day 4 and hunched posture by day 5. In addition, reduced water consumption was seen at 400 ppm.