Tallow, lithium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

The study was performed between 21 April 2010 and 01 June 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Justification for type of information:

See IUCLID section 13 for category and read across justification

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids C18-(unsaturated) lithium salts

Cas Number:

502962-81-4

IUPAC Name:

Fatty acids C18-(unsaturated) lithium salts

Test material form:

solid

Details on test material:

- Batch number: Not reported
- Expiry date: Not reported

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Oxon, UK.
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: Overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet (supplied by Harlan UK Limited, Oxon, UK) was allowed ad libitum throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: Acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: Day 1 To: Day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water to give a dose level of 300 or 2000mg/kg bodyweight.
- Amount of vehicle (if gavage): Not stated
- Justification for choice of vehicle: Distilled water was the preferred vehicle of the test method.
- Lot/batch no. (if required): Not stated
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Doses:

Following a sighting test at a dose levels of 300 and 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No. of animals per sex per dose:

1 female at 300 mg/kg bw
1 female at 2000 mg/kg bw
4 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight.

Results and discussion

Preliminary study:

A sighting test at a dose levels of 300 and 2000 mg/kg bw was performed.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: Signs of systemic toxicity noted were hunched posture, pilo-erection, ataxia, noisy respiration, sneezing and increased salivation. Animals appeared normal 2, 5 or 10 days after dosing.

Gross pathology:

No abnormalities were noted at necropsy.
Individual necropsy findings are given in Table 6 (in any other information section)

Any other information on results incl. tables

Table1              Individual Clinical Observations and Mortality Data -300mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

Table 2              Individual Bodyweights and Bodyweight Changes -300mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	180	202	212	22	10

Table 3              Necropsy Findings -300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected

Table 4              Individual Clinical Observations and Mortality Data -2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	H	H	HPA	HPA	HPA	HA	HA	H	0	0	0	0	0	0	0	0	0	0
	3-0 Female	HRnS	HRnS	HPRn	HPRn	HARn	Rn	Rn	RnRs	RnRs	RnRs	RnRs	RnRs	RnRs	0	0	0	0	0
	3-1 Female	H	HPA	HPA	HP	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	H	HPA	HPA	HA	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	H	HA	HA	HA	H	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

H =      Hunched posture

P =      Pilo-erection

A =      Ataxia

Rn =   Noisy respiration

Rs =   Sneezing

S =     Increased salivation

Table 5              Individual Bodyweights and Bodyweight Changes -2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2-0 Female	176	180	193	4	13
	3-0 Female	176	178	189	2	11
	3-1 Female	165	184	190	19	6
	3-2 Female	186	198	213	12	15
	3-3 Female	172	182	202	10	20

Table 6              Individual Necropsy Findings-2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected
	3-3 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

other: Not classified (EU CLP (EC) No 1272/2008) and Category 5 (UN GHS version 7, 2017)

Remarks:

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted 17 December 2001)

- Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. 

Following a sighting test at dose levels of 300 mg/kg bw and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations.

Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg bw were hunched posture, pilo-erection, ataxia, noisy respiration, sneezing and increased salivation. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg bw.

Bodyweight. 

All animals showed expected gains in bodyweight.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute oral median lethal dose (LD₅₀) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.