Lithium fluoride

Endpoint summary

Description of key information

Based on the findings in an acute oral toxicity study an LD50 of 706 mg/kg bw was determined for male and female rats.

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

Study period:

1988-12-28 to 1989-01-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

November 1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot No.of test material: Lot 129, Drums 1 - 10

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms, Germantown, New York
- Weight at study initiation: 201 - 291 g
- Fasting period before study: overnight prior to dosing
- Housing: the animals were individually housed in stainless steel suspended rat cages
- Diet: Purina Laboratory Rodent Chow 5001 ad libitum
- Water: tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 66 °F - 73 °F
- Humidity: 24 % to 63 %
- Photoperiod: 12 hour fluorescent light and 12 hour dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 % (weight/volume) solution with tap water

Doses:

males: 500, 700, 1000 mg/kg
females: 500, 1000, 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for mortality and clinical signs at 0.5, 1, 2, 3, 4 and 6 hours on the day of dosing and twice daily thereafter for thirteen days; on day 14 they were observed once. Body weights were taken on days 0, 7 and 14 of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights.

Sex:

male

Dose descriptor:

LD50

Effect level:

608 mg/kg bw

Based on:

test mat.

95% CL:

ca. 448 - <= 768

Sex:

female

Dose descriptor:

LD50

Effect level:

1 004 mg/kg bw

Based on:

test mat.

95% CL:

ca. 472 - <= 1 535

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

706 mg/kg bw

Based on:

test mat.

95% CL:

ca. 453 - <= 959

Mortality:

Mortality in males
500 mg/kg bw dose group - 1/5
700 mg/kg bw dose group - 4/5
1000 mg/kg bw dose group - 5/5
Mortality in females
500 mg/kg bw dose group - 1/5
1000 mg/kg bw dose group - 2/5
2000 mg/kg bw dose group - 5/5

Clinical signs:

other: Clinical signs commonly observed during the study included ataxia, tremors, diarrhea, abdominogenital staining, chromorhinorrhea and chromodacryorrhea. The onset of signs began approximately 1 hour after dosing and continued to be observed until day 6 of

Gross pathology:

Gross internal necropsy findings observed in decedents included blood in the intestines of several rats, one of which also had a stomach which was distended with gas. All surviving animals appeared normal at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the study, a male LD50 value of 608 mg/kg bw, a female LD50 value of 1004 mg/kg bw, and a combined LD50 value of 706 mg/kg bw were obtained when orally administered as a 25 % (weight/volume) solution in tap water.

Executive summary:

Groups of Sprague-Dawley rats consisting of five males and/or five females were orally administered graded dosages of the test substance as a 25 % (weight/volume) solution in tap water by gavage according to OECD Guideline 401. Males were administered with 500, 700 and 1000 mg/kg bw. Females were administered with 500, 700 and 2000 mg/kg bw.

Mortality occurred in all dose groups. By male rats in dose groups 500, 700 and 1000 mg/kg bw out of 5 rats per dose group 1, 4, 5 rats died respectively. By female rats in dose groups 500, 1000 and 2000 mg/kg bw out of 5 rats per dose group 1, 2, 5 rats died respectively. The predominant clinical signs were ataxia, tremors, diarrhea, abdominogenital staining, chromorhinorrhea and chromodacryorrhea. Most signs of toxicity subsided by day 6 of the study. All surviving animals gained weight by day 14 of the study.

Gross internal necropsy findings observed in decedents included blood in the intestines of several rats, one of which also had a stomach which was distended with gas. Animals which survived treatment and were sacrificed on day 14 appeared normal when necropsied.

Under the conditions of the study, a male LD50 value of 608 mg/kg bw, a female LD50 value of 1004 mg/kg bw, and a combined LD50 value of 706 mg/kg bw were obtained when orally administered as a 25 % (weight/volume) solution in tap water.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

706 mg/kg bw

Quality of whole database:

Acceptable and well documented study report, compliant to guideline.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Testing for acute toxicity via the inhalation route is not applicable as human exposure via inhalation is unlikely. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5.2 testing is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The test substance has a high melting point (848 °C) and a very low vapour pressure (1.22E-021 Pa).
No signs of systemic effects were observed in two acute studies with the structurally similar substances lithium bromide and lithium chloride. Both tests showed that toxic effects due to inhalation can be excluded, although the water solubility favors the uptake of the test substance via the mucous membrane of the respiratory tract.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII, Section 8.5.3, Column 2 of regulation (EC) No. 1907/2006 (REACH) testing by the dermal route is appropriate if : 1. Inhalation of the substance is unlikely; and 2. skin contact in production and/or use is likely; and 3. the physicochemical and toxicological suggest a potential for a significant rate of absorption through the skin. Lithium fluoride is an inorganic salt with a molecular weight of < 100 and is soluble in water. A log Pow was estimated to be 0.23 for the corresponding anion hydrofluoric acid proving low lipophilicity. Only lipophilic substances are able to penetrate the intact skin barrier. Polar substances and ionic compounds like lithium fluoride are not able to pass the intact epidermis at all. No signs of systemic toxicity were observed in the acute dermal toxicity studies conducted with the read across source substances lithium bromide and lithium chloride. Additionally, lithium fluoride did not show any skin irritating or skin corrosive properties in two in vitro studies (please refer to IUCLID section 7.3.1). Hence, the penetration is not facilitated due to damage of the skin surface. Therefore, it can be reliably assumed that lithium fluoride is not able to pass the stratum corneum. Further in vivo testing would be unethical and cannot be scientifically justified with the above argumentation.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

Groups of Sprague-Dawley rats consisting of five males and/or five females were orally administered graded dosages of the test substance as a 25 % (weight/volume) solution in tap water by gavage according to OECD Guideline 401 and EPA 81-1 acute oral. Males were administered with 500, 700 and 1000 mg/kg bw. Females were administered with 500, 700 and 2000 mg/kg bw.

Mortality occurred in all dose groups. By male rats in dose groups 500, 700 and 1000 mg/kg bw out of 5 rats per dose group 1, 4, 5 rats died respectively. By female rats in dose groups 500, 1000 and 2000 mg/kg bw out of 5 rats per dose group 1, 2, 5 rats died respectively. The predominant clinical signs were ataxia, tremors, diarrhea, abdominogenital staining, chromorhinorrhea and chromodacryorrhea. Most signs of toxicity subsided by day 6 of the study. All surviving animals gained weight by day 14 of the study.

Gross internal necropsy findings observed in decedents included blood in the intestines of several rats, one of which also had a stomach which was distended with gas. Animals which survived treatment and were sacrificed on day 14 appeared normal when necropsied.

Under the conditions of the study, a male LD50 value of 608 mg/kg bw, a female LD50 value of 1004 mg/kg bw, and a combined LD50 value of 706 mg/kg bw were obtained when orally administered as a 25 % (weight/volume) solution in tap water.

Acute inhalation toxicity

Testing for acute toxicity via the inhalation route is not applicable as human exposure via inhalation is unlikely. According to REACH Regulation No. 1907/2006, Annex VIII, 8.5.2 testing is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The test substance has a the high melting point (848 °C) and a very low vapour pressure (1.22E-021 Pa).

Acute dermal toxicity

In accordance with Annex VIII, Section 8.5.3, Column 2 of regulation (EC) No. 1907/2006 (REACH) testing by the dermal route is appropriate if :

1. Inhalation of the substance is unlikely; and

2. skin contact in production and/or use is likely; and

3. the physicochemical and toxicological properties suggest a potential for a significant rate of absorption through the skin.

Lithium fluoride is an inorganic salt with a molecular weight of < 100 and is soluble in water. A log Pow was estimated to be 0.23 for the corresponding anion hydrofluoric acid proving low lipophilicity. Only lipophilic substances are able to penetrate the intact skin barrier. Polar substances and ionic compounds like lithium fluoride are not able to pass the intact epidermis at all.

No signs of systemic toxicity were observed in the acute dermal toxicity studies conducted with the read across substances lithium bromide and lithium chloride. Additionally, lithium fluoride did not show any skin irritating or skin corrosive properties in two in vitro studies (please refer to IUCLID section 7.3.1). Hence, the penetration is not facilitated due to damage of the skin surface.

Therefore, it can be reliably assumed that lithium fluoride is not able to pass the stratum corneum. Further in vivo testing would be unethical and cannot be scientifically justified with the above argumentation.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified as acute toxicity cat. 4, H302: "Harmful if swallowed" under Regulation (EC) No 1272/2008.