Lithium salicylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Jul 2017 - 26 Dec 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

Lot # 17-24168
Expiration: 20 Mar 2019
White Powder

Specific details on test material used for the study:

Source: ExxonMobil Research & Engineering (Paulsboro, NJ)
Lot # 17-24168
Expiration Date: 20 March 2019

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Raleigh NC and Stone Ridge NY
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 188 - 261 grams
- Fasting period before study: 16 - 20 hours
- Housing: Individually housed in suspended wire-bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet No. 5012)
- Water (e.g. ad libitum): Tap water, ad-libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Range during study duration: 18.38 to 22.38
- Humidity (%): Range during study duration: 20.3 to 89.7%. While the humidity intermittently exceeded 70%, the fluctuations occurred gradually, during which time the temperature remained relatively consistent and within range.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 30 Aug 2017 To: 20 Oct 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Distilled

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): Dose volume was based on fasted body weight of each animal, and the dry weight of the test article.
- Justification for choice of vehicle: Per OECD TG 425 with respect toformulation of the dosing preparations, the use of an aqeous solution is recommended wherever possible; substance was soluble in vehicle throughout duration of test.
- Expiration Date: 21 Jul 2018
- Purity: Filtered through 5-micron mesh system

Doses:

Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal died, additional animals were dosed, one at a time, by a single ordered dose progression (factor 3.2). This resulted in doses of 175, 550 and 2000 mg/kg bodyweight

No. of animals per sex per dose:

2000 mg/kg bw: 3 females; 550 mg/kg bw: 4 females, 175 mg/kg bw: 2 females

Control animals:

no

Details on study design:

Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal died, additional animals were dosed, one at a time, by a single ordered dose progression.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily thereafter for 14 days for toxicity and pharmacological effects. Animals were observed twice daily for mortality on Day 1 to Day 14, with the exception of Animals 3 and 8 which were only observed once on study day 5. Body weights were recorded pre-test, weekly, and at death or termination in the survivors.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical observations included, but were not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects including tremors and convulsions, changes in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking backwards).

Statistics:

The LD50 and 95% Confidence Limits were calculated according using AOT425 StatPgm provided by the U.S. EPA.

Results and discussion

Preliminary study:

Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal died, additional animals were dosed, one at a time, by a single ordered dose progression.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

> 209.7 - < 1 220

Mortality:

All three female rats died within approximately 4 hours following the single 2000 mg/kg bw oral dose. Two out of four female rats died by Day 1 following a single 550 mg/kg bw oral dose. Both female rats survived following a single 175 mg/kg bw oral dose.

Clinical signs:

other: At 2000 mg/kg bw abnormal physical signs included soiling and wetness of the anogenital area, ataxia, piloerection, prostration, lethargy, hunched posture, wetness of the nose/mouth area, and yellow diarrhea. At 550 mg/kg bw, abnormal physical signs inc

Gross pathology:

The gross necropsy of females receiving a single oral dose of 2000 mg/kg bw revealed darker than normal liver, and abnormalities of the gastrointestinal tract. Gross necropsy of the females that died folloing single oral dose of 550 mg/kg bw revealed abnormalities of the gastrointestinal tract, pale areas and darker than normal liver, darker than normal lungs, dark areas on the pancreas, and dark areas on the left kidney. The gross necropsy of the two surviving females following a single oral dose of 550 mg/kg bw revealed no observable abnormalities. The gross necropsy revealed no observable abnormalities in either female receiving a single oral dose of 175 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for Dilithium Salicylate following oral intubation was established at 550 mg/kg bw for females. This finding warrants classification of Dilithium Salicylate as an acute oral toxicant Category 4 under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

Dilithium Salicylate was administered via oral intubation to Sprague-Dawley rats in an Up and Down ordered progression at doses of 2000, 550, and 175 mg/kg to assess the acute oral toxicity. Animals were observed daily for 14 days post dosing. Overt signs of toxicity were apparent at a dose level of 2000 mg/kg and mortality was observed in all three females within 4 hours of dosing. The incidence of death was considered dose related. All animals which survived to study termination were free of abnormalities at postmortem examination (two females at the 550 mg/kg bw dose level, and 2 at the 175 mg/kg bw dose level). All surviving animals displayed increases in body weight over their day 0 values. The LD50 for Dilithium Salicylate based on this data was established at 550 mg/kg bw for females. This finding warrants classification of Dilithium Salicylate as an acute oral toxicant Category 4 under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).