Lithium salt of branched-aliphatic dicarboxylic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-07-08 to 2014-08-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted under GLP conditions in accordance with the OECD guideline No 423 (2001).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(May, 2008)

Deviations:

no

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar Crl: WI (Han)
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: young adult animals (8-9 weeks)
- Weight at study initiation: 143 - 185 g
- Fasting period before study: overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: group housing of 3 animals per cage
- Diet (e.g. ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: assumed low toxic effects

Doses:

2000 mg/kg (10 mL/kg) body weight.
300 mg/kg (10 mL/kg) body weight.

No. of animals per sex per dose:

3 animals per dose (total of 12 animals)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead or sacrificed after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, three out of six animals were found dead on Day 2 or 3.
At 300 mg/kg, no mortality occurred.

Clinical signs:

At 2000 mg/kg, lethargy, hunched posture, piloerection, ptosis and/or diarrhea were noted for the animals between Days 1 and 9.
At 300 mg/kg, hunched posture and/or piloerection, were noted for the animals on Day 1.

Body weight:

At 2000 mg/kg, one of the surviving animals showed slight body weight loss between Days 1 and 8. Other animals showed expected body weight gain.

Gross pathology:

At 2000 mg/kg, abnormalities of the stomach and small intestines (contents: gelatinous) were found in one of the animals found dead.

Any other information on results incl. tables

Table 1. Mean body weights

Sex / dose level	Mean weight +/- St.Deviation (g)
	Day 1	Day 8	Day 15
Females 2000 mg/kg	153 +/- 9	166 +/- 8	196 +/- 1
Females 2000 mg/kg	176 +/- 11	174	198
Females 300 mg/kg	177 +/- 8	198 +/- 9	209 +/- 7
Females 300 mg/kg	157 +/- 7	187 +/- 6	202 +/- 11

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of Lithium salt of branched-aliphatic dicarboxylic acid in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Executive summary:

The oral LD50 value of Lithium salt of branched-aliphatic dicarboxylic acid in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Based on these results:

- according to the Globally Harmonised System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments),

Lithium salt of branched-aliphatic dicarboxylic acid should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.

- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments),

Lithium salt of branched-aliphatic dicarboxylic acid should be classified as Category 4 and should be labelled as H302: Harmful if swallowed.