Potassium fluoride

Endpoint summary

Description of key information

Based on the reported acute oral LD50 values for sodium fluoride in experimental animals, fluoride salts are considered moderately toxic if ingested.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according generally valid procedures and all parameters described were closely related or comparable to guideline methods.

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

- a control group was not included.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Portage, MI, USA
- Weight at study initiation: 190 - 300 g (fasted weight)
- Fasting period before study: No data

ENVIRONMENTAL CONDITIONS
- Followed approved Standard Operating Procedures of the test facility

Route of administration:

oral: gavage

Vehicle:

other: deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4.0% w/v in deionized water
- Amount of test substance and vehicle dosed (if gavage): 2.86, 3.4, 4.0 or 5.6 mL/kg body weight
- Justification for choice of vehicle: test substance was readily soluble up to 4% in water

Doses:

Dose levels evaluated were: 114, 136, 160 and 224 mg NaF/kg body weight.

No. of animals per sex per dose:

10 female rats per dose

Control animals:

no

Details on study design:

After a single oral gavage dose, all animals were observed for mortality at frequent intervals during the first 4 hours after dosing (at least once during the first 30 minutes) and daily thereafter for the next 14 days.

Statistics:

The LD50 value and 95% confidence limits were calculated by the Probit Method [ J. Finney, Probit Analysis, 3rd Ed., Cambridge Univ. Press, 1971, pp. 50-90] by use of the computer program BLISS17 [Fortran version of BLISS17 program, written by D.J. Finney].

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 148.5 mg/kg bw

95% CL:

116.3 - 185.5

Mortality:

Dose Level Number of Deaths
114 mg/kg 2/10
136 mg/kg 4/10
160 mg/kg 7/10
224 mg/kg 8/10
336 mg/kg 8/8
500 mg/kg 8/8

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 for sodium fluoride in female Sprague-Dawley rats was 148.5 mg/kg body weight with 95% confidence limits of 116.3 - 185.5 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

248 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

May 1995 - June 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study comply with the Principles of GLP OECD and was conducted in accordance with EPA OPP 81-4 guideline.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Remarks:

GLP statement included

Limit test:

no

Species:

rat

Sex:

male/female

Route of administration:

inhalation

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.52, 1.02 and 1.98 mg/L

No. of animals per sex per dose:

five males and five females per group

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at least daily for signs of gross toxicity and mortality; bodyweights recorded just prior to exposure (day 0) and on days 7 and 14 (i.e. termination) or after death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality at 0.52 mg/L: Total 2/10 (i.e. Males 0/5; Females 2/5)
Mortality at 1.02 mg/L: Total 5/10 (i.e. Males 1/5; Females 4/5)
Mortality at 1.98 mg/L: Total 8/10 (i.e. Males 3/5; Females 5/5)

Clinical signs:

other: All animals, irrespective of their exposure level, displayed clinical signs such as: ocular and nasal discharge facial staining ano-genital staining abnormal respiration abnormal posture pilo-erection hypoactivity. Survivors from all exposure groups reco

Body weight:

Some surviving animals lost bodyweight through day 7, however all gained weight over the entire 14 -day observation period.

Gross pathology:

- Gross necropsy of decedents:
discoloration of the lungs, gastro-intestinal tract, liver and spleen; edema of the lungs; distention of the gastro-intestinal tract; fluid in the stomach and/or rigor mortis.

- Gross necropsy of survivors from all groups was generally unremarkable. Two survivors from the group exposed to 0.52 mg/L exhibited dark red foci on the lungs.

Conclusions:

An acute inhalation toxicity study was conducted with rats to determine the toxicity via inhalation for NaF and the defined LC50 value is 1.00 mg/L.

Executive summary:

An acute inhalation toxicity study was conducted with rats to determine the toxicity via inhalation for NaF.

After establishing the desired generation procedures during pre-test trials, 30 healthy rats were selected and equally distributed into three exposure groups of five males and five females each. Exposure values were 0.52, 1.02 and 1.98 mg/L and each test group was exposed for four hours. Chamber concentration and particle size distribution were determined periodically during each exposure.

The animals were observed for signs of gross toxicity and mortality at least daily for 14 days. Bodyweights were recorded just prior to exposure (day 0) and again on days 7 and 14 (i.e. termination) or after death. Necropsies were performed on all animals.

The mortality at each exposure level is provided below:

Exposure levelmg/L	Mortality
	Males	Females	Total
0.52	0/5	2/5	2/10
1.02	1/5	4/5	5/10
1.98	3/5	5/5	8/10

Following exposure all animals, irrespective of their exposure level, displayed clinical signs such as: ocular and nasal discharge, facial staining, ano-genital staining, abnormal respiration, abnormal posture, pilo-erection and hypoactivity. Survivors from all exposure groups recovered from these symptoms by day 12 of the study. Although some surviving animals lost bodyweight through day 7, all gained weight over the entire 14 -day observation period. Gross necropsy of the decedents revealed discoloration of the lungs, gastro-intestinal tract, liver and spleen, edema of the lungs, distention of the gastro-intestinal tract, fluid in the stomach and/or rigor mortis. Gross necropsy of the survivors from all groups was generally unremarkable. Two survivors from the group exposed to 0.52 mg/L exhibited dark red foci on the lungs.

Based on the results, the acute inhalation toxicity study defined LC50 of NaF is 1.00 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 674 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comply with the GLP as defined in 40 CFR 160: U.S EPA Good Laboratory Practice Standards: Pesticide Programs (FIFRA) and OECD Principles of Good Laboratory Practice C(81)30 (Final) Annex 2.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab animals, Scottdale, PA on May 8, 1995
- Age at study initiation: Not indicated
- Weight at study initiation: Males: 240-256 g; Females: 218-241 g
- Housing: One animal in one stainless steel cage
- Diet: Purina Rodent Chow 5012
- Water: Ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-71
- Humidity (%): Not indicated
- Air changes (per hr): Not indicated
- Photoperiod (hrs dark / hrs light): 12/12

TEST DATES: From: 23 May 1995 - To: 6 June 1995 (14 days)

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 2 x 3 cm
- % coverage: 10% of the body surface
- Type of wrap if used: Application site covered by adhesive backed-gauze patch and held in place by plaster (strapping)

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: No

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

10 healthy rats : 5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations, weighing before application and on days 7 and 14 (termination)
- Necropsy of survivors performed: Yes
- Other examinations performed: Macroscopic abnormalities at necropsy

Statistics:

No

Preliminary study:

No

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: dermal irritation and/or discoloration at the dose site One female exhibited facial staining, diarrhea and emaciation between days 2 and 6.

Gross pathology:

No macroscopic abnormalities

Other findings:

No

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material at 2000 mg/kg body weight caused transient facial staining, diarrhea and emaciation in only one of five females. All other animals appeared active and healthy. There is no need to classify or label the test material for acute dermal toxicity.

Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for Composite NaF, to produce toxicity after topical application. Based on the results of testing, the single dose Acute Dermal Toxicity LD50 of the test substance is greater than 2000 mg/kg of bodyweight when applied as received, moistend with distilled water.

Two thousand milligrams of the test substance per kilogram of bodyweight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for signs of gross toxicity and mortality at least once daily for 14 days. Bodyweight were recorded just prior to application and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived and gained bodyweight during the study. One female exhibited facial staining, diarrhea and emaciation between days 2 and 6. All other animals appeared active and healthy. Apart from the dermal irritation and/or discoloration noted at the dose site of all animals, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. Gross necropsy findings at terminal sacrifice were generally unremarkable.

Conclusion:

The Single Dose Acute Dermal LD50 of Composite NaF is greater 2000 mg/kg of bodyweight when applied as received, moistened with distilled water.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 348 mg/kg bw

Additional information

In the key acute oral toxicity studies (Proctor & Gamble, 1984, 1985), the LD50 for sodium fluoride in male Sprague-Dawley rats was reported to be 223 mg/kg body weight with 95% confidence limits of 177 - 272 mg/kg body weight and the LD50 for sodium fluoride in female Sprague-Dawley rats was reported to be 148.5 mg/kg body weight with 95% confidence limits of 116.3 - 185.5 mg/kg body weight, respectively. The acute oral LD50 for ammonium fluoride in Sprague-Dawley rats was reported (Riedel-de Haen AG, 1994) to be greater than 25 mg/kg body weight, but less than 2000 mg/kg body weight. In the key acute inhalation toxicity study (Wnorowski 1995), the LD50 for sodium fluoride in males and females healthy rats was reported to be 1.00 mg/L. In the key acute dermal toxicity study (Wnorowski 1995), the LD50 for sodium fluoride in males and females healthy rats was reported to be above 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Key study, conducted with test substance NaF. LD50 for female rats was lower than for male rats, thus the LD50 for females is taken forward. Assuming that the driver for toxicity is the fluoride ion, the established LD50 for NaF (148.5 mg/kg) was re-calculated to KF, resulting in 248 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
Key study, conducted with test substance NaF. Assuming that the driver for toxicity is the fluoride ion, the established LC50 for NaF (1 mg/L or 1000 mg/m³) was re-calculated to KF, resulting in 1674 mg/m³.

Justification for selection of acute toxicity – dermal endpoint
Key study, conducted with test substance NaF. Assuming that the driver for toxicity is the fluoride ion, the established LD50 for NaF (> 2000 mg/kg, limit test) was re-calculated to KF, resulting in > 3348 mg/kg.

Justification for classification or non-classification

According to EU classification, labelling and packaging of substances and mixtures (CLP) regulations (EC no 1272/2008), fluorides should be classified as acute toxic class 3 for acute oral toxicity.