Dilithium glutarate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003/10/15 - 2003/11/18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentanedioic acid, lithium salt (1:2)

EC Number:

608-319-2

Cas Number:

29126-51-0

Molecular formula:

C5H8O4.2Li

IUPAC Name:

Pentanedioic acid, lithium salt (1:2)

Test material form:

solid: particulate/powder

Details on test material:

White powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ExxonMobil Research and Engineering (Paulsboro, New Jersey)
- Expiration date of the lot/batch: July 2008

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Solubility and stability of the test substance in the solvent/vehicle: the test substance was soluble in the vehicle at the concentrations used during the study

Test animals

Species:

rat

Strain:

other: crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

ENVIRONMENTAL CONDITIONS:
TEST ANIMALS
- Source: CHarles River Laboratories
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10-13 weeks
- Weight at study initiation: 211-253 grams
- Fasting period before study: 18 hours
- Housing: single housed
- Diet (e.g. ad libitum): PMI Certified Rodent Diet Meal 5002, ad libitum
- Water (e.g. ad libitum): Deionized water, ad libitum
- Acclimation period: 7-28 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64 - 72 degrees Fahrenheit
- Humidity (%): 30 to 70 percent relative humidity
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

IN-LIFE DATES: From: 2003/10/15 To: 2003/11/18

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Deionized

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 0.88 mL/kg, 2.75 mL/kg, and 10 mL/kg for dose groups 175 mg/kg, 550 mg/kg and 2000 mg/kg respectively
- Justification for choice of vehicle: Test substance was soluble in chosen vehicle over duration of study

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg fasted body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Per OECD Test Guideline 425 a single female was initially dosed with 2,000 mg/kg.

Doses:

175 mg/kg, 550 mg/kg and 2,000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded on the day prior to dosing, on the day of dosing (Day 0), on Day 7, and Day 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Animals were observed for mortality twice daily. Clinical observations were made at 30 minutes, 1, 2, 4, and 6 hours after dosing and once per day

Statistics:

Statistical analyses included calculating the means and standard deviations of body weight and body weight change by group and sex. The oral median lethal dose (LD50) was calculated using the AOT425StatPgm software.

Results and discussion

Preliminary study:

Per OECD test guideline 425, one female was initially dosed with 2,000 mg/kg, this animal was found dead on Day 1. The subsequent animal was then treated with 175 mg/kg as the standard starting dose to avoid biasing the LD50 towards 2000 mg/kg.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 098 mg/kg bw

Based on:

test mat.

95% CL:

550 - 2 000

Clinical signs:

Clinical signs were only evident in the 2000 mg/kg animals. These signs included hypothermia, prostration, hypopnea, dyspnea, ocular discharge, soft stool, mucoidal stool and staining of the fur in the ano-genital area.

Gross pathology:

Gross postmortem examination of the animals that were found dead during the study included ano-genital staining, small intestine and cecum distended with gas
and yellow liquid and the stomach distended with gas and yellow liquid. All other animals were free of gross postmortem abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 for Dilithium Glutarate following oral intubation was established at 1098 mg/kg for females. These findings warrant classification of Dilithium Glutarate as an acute oral toxicant Category 4 under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

Dilithium Glutarate was administered via oral intubation to Crl:CD(SD) rats (8 females) at doses of 175, 550, and 2000 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. Mortality was observed only at 2000 mg/kg and all of the animals that succumbed following administration of Dilithium Glutarate died within 1 day of dosing. The incidence of death was considered dose related. All animals which survived to study termination were free of abnormalities at postmortem examination. All surviving animals displayed increases in body weight over their Day 0 values. The LD50 for Dilithium Glutarate was established at 1098 mg/kg for females. These findings warrant classification of Dilithium Glutarate as an acute oral toxicant Category 4 under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).