Dilithium oxide

Endpoint summary

Description of key information

Acute toxicity: inhalation:

LC50 (4h) 0.94 mg/L aerosol

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Remarks:

/Lov

Sex:

male/female

Details on test animals or test system and environmental conditions:

Four groups of 8 male and 8 female laboratory-raised F344/Lov rats, aged 9 to 12 weeks, were used in the two series of lithium exposures. A single control group consisting of the same number of animals was shared between the two lithium exposure series. The animals were housed two per cage in filter-topped polycarbonate plastic cages (48 X 24 X 20 cm high) with hardwood chip bedding. Rooms were maintained at 68- 72°F, with a relative humidit of 20-50% and a 12-hr light: dark cycle with light starting at 6:00 AM Food (Lab Blox, Allied Mills, Chicago, III.) and water from bottles with sipper tubes were provided ad libitum. The animals were randomly assigned into exposure groups by body weight. Any animal appearing in poor health or having an initial body weight beyond two standard deviations of the group mean for each sex was not used in the study.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Remarks:

Rochester-type chamber, 1m³

Vehicle:

clean air

Remarks:

and argon

Mass median aerodynamic diameter (MMAD):

>= 0.54 - <= 0.68 µm

Geometric standard deviation (GSD):

>= 1.36 - <= 1.56

Remark on MMAD/GSD:

The aerosol particles showed the typical branched-chain structure of vaporizationcondensation aerosols of metal oxides

Details on inhalation exposure:

Mixture of Li2O and LiOH, contained limited (up to 25%) Li2CO3, generated under conditions of low relative humidity (<25%).
Aerosols flowed through the animal exposure chamber at 200 liters/min.

Analytics: The mass concentration of aerosol in the chamber was monitored by drawing filter samples (0.8 µm Acropore filters, Gelman Instrument Co., Ann Arbor, Mich.) every 15 min throughout the exposure. The filters were weighed with an electrobalance (Model 27. Cahn Instruments. Cerntos. Calif.). An optical aerosol monitor (Model P-5A. Environmental Monitoring Systems, Knoxville, Tenn.) provided real-time monitoring of the aerosol concentration in the chamber.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

500, 750, 1000 and 1500 mg/m³

No. of animals per sex per dose:

8

Control animals:

yes

Details on study design:

- Body weights:
Body weights were measured on Days 0 (preexposure). 1, 5, 8, 14, 21. and 28. Clinical examinations for signs of toxicity (respiratory difficulty, encrustation of blood or mucus around the eyes, nose, or mouth, righting reflexes, etc.) were performed daily.

- Sacrifice and necropsy:
At 14 days after exposure, a portion of the surviving animals were selected randomly for sacrifice by ip injection of a lethal dose of T-61 euthanasia solution (American Hoechst Co., Sommerville. N.J.). The remaining animals were observed for an additional 14 days and then sacrificed. A complete necropsy was performed on all animals. Lung, liver, kidney, and thymus weights were recorded. The thymus, liver, kidneys, and respiratory tract, from nares to lungs, were removed and fixed in 10% neutral buffered Formalin for histopathology. Tissue sections stained with hematoxylin and eosin were prepared for light microscopy.

Statistics:

The 14-day LC50 values were calculated for the male and female rats separately and combined using probit analysis (Finney, 1964). Because the exposures were not concurrent, and because animals died at various times after exposure, only qualitative comparisons could be made for body weight and organ weight data.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

940 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 730 - <= 1 200

Exp. duration:

4 h

Remarks on result:

other: 14-day observation period

Mortality:

The male rats died earlier than the female rats exposed concurrently.

Clinical signs:

bodyweight loss

Remarks:

excessive salivation and nasal mucus secretion. Coughing and choking, respiratory difficulty, including audible mouth breathing, encrustation of blood and mucus around the eyes and nose, slowing of the righting reflex, and general lethargy.

Body weight:

Rapid and persistent weight loss was characteristic of animals in the higher exposure concentration groups.
Animals exposed to only 500 mg/m³ exhibited transient and reversible weight losses.

Gross pathology:

Alterations were seen in the larynges, turbinates, and lungs of exposed animals. There was a clear dose-response pattern for both males and females in all exposure groups. Laryngeal lesions were the most consistent alterations with all of the lithium aerosols tested. The principal change was necrotic laryngitis. The lesion was segmental, affecting primarly the epiglottis and anterior portions of the larynx with the more distal portions often entirely spared. In affected regions there was mucosal erosion and/or ulceration, submucosal inflammation with extension into laryngeal musculature, and occasional thrombosis of submucosal vessels. There was bacterial colonization of ulcerated surfaces and occasional laryngeal foreign bodies (hair fragments) were present. Mucosal surfaces immediately adjacent to necrotic zones frequently exhibited squamous metaplasia. The majority of animals with laryngeal pathology also had turbinate lesions. Occasional animals had turbinate lesions with no evidence of laryngeal involvement.
Turbinate lesions consisted of focal to patchy erosive to ulcerative rhinitis. The nasal cavity often contained an exudate formed of aggregates of neutrophils enmeshed in mucus. Areas of squamous metaplasia were found within the nasal mucosa. Bacterial colonization and occasional nasal foreign bodies (hair fragments and keratinous debris) were observed. Pulmonary lesions were of varying severity and were present only in animals with laryngeal and/or turbinate involvement. The mildest lesions were rare and consisted of acute multifocal terminal bronchiolitis and associated alveolitis. More severe lesions consisted of patchy diffuse necrotizing pneumonia, often associated with inhaled foreign bodies (hair fragments and keratinous debris) and bacterial colonies. Thymic lesions were also present. The principal change was depletion of cortical lymphocytes with resultant organ atrophy. Multifocal hemorrhage was a common accompaniment.

Other findings:

Several animals had swollen, inflammed external genitalia.
No clear dose-response relation could be discerned for absolute organ weight or organ weight-to-body weight ratios in the exposed animals.

Interpretation of results:

other: Category 3 based on EU GHS criteria

Remarks:

toxicity based on corrosion

Conclusions:

The 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730-1200) mg/m³ (0.94 mg/L) for the lithium oxide and hydroxide mixture and 960 (830-1200) mg/m³ for the lithium hydroxide aerosols.

Executive summary:

Male and female F344/Lov rats were exposed to aerosols of Lithium combustion aerosols (Case 3: predominantly lithium monoxide with some lithium hydroxide and about 12% lithium carbonate). The 14-day LC50 values (with 95% confidence limits) determined after 4-hr exposures were 940 (730-1200) mg/m³ (0.94 mg/L) for the lithium oxide and hydroxide mixture and 960 (830-1200) mg/m³ for the lithium hydroxide aerosols. Histopathologic lesions were observed in the nasal turbinates, larynx, and occasionally in the lungs with both aerosols. The most prominent lesions were necrotizing laryngitis and ulcerative rhinitis. Pulmonary lesions represented a secondary extension of the upper respiratory tract lesions rather than a primary manifestation of lithium toxicity. The similarities in the LC50 values and also in the histopathologic lesions observed suggest that any Li2O in the aerosol reacted rapidly with water vapor in the respiratory tract to form LiOH prior to deposition. The type of lesion, primarily necrotizing, supports the suggestion that combustion aerosols of alkali metals exert their toxicity by producing localized areas of high pH upon contact with the tissue, thereby causing protein coagulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

0.94 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

good quality

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Due to the corrosive properties of the substance, acute toxicity test are waived. One result of an inhalation study on rats is available revealing the stong basic corrosion properties of the substance. In this study the LC50 (4h) was determined to be 0.94 mg/L aerosol leading to a classification as Category 3 (H331) according to Regulation (EC) No 1272/2008. As the mechanism of toxicity is corrosivity, the test item need to be labelled in addition as EUH071 ‘corrosive to the respiratory tract’.