lithium manganese iron phosphate

Endpoint summary

Description of key information

Acute oral toxicity:
LD50 > 2000 mg/kg bw, rat (female), OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF guidelines, Huygevoort (2006)
Acute inhalation toxicity:
LC50 > 3.2 mg/L, rat (male/female), OECD 403, EU Method B.2, EPA OPPTS 870.1300 and JMAFF, Janssen (2007)
Acute dermal toxicity:
LD50 > 2000 mg/kg bw, rat (male/female), OOECD 402, EU Method B.3 and EPA OPPTS 870.1200, Lükenhaus (2012)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 October 2006 - 13 December 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: 222 - 258 g (Day 1)
- Fasting period before study: yes (food was witheld overnight - for a maximumof 20 hours - prior to dosing until 3-4 hours after administration of the test material)
- Housing: animals were housed in groups of 3 in Macrolon cages furnished withy sterilised sawdust and paper as cage-enrichment.
- Diet: pelleted rodent diet, SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany (ad libitum)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 23.0 °C
- Humidity (%): 41 - 91%
- Air changes (per hr): ca. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Route of administration:

oral: gavage

Vehicle:

other: Water (Milli-U)

Details on oral exposure:

The formulations were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

Doses:

2000 mg/kg (10 mL/kg) bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

STUDY DESIGN
The toxicity of the test material was assessed by stepwise treatment of groups of 3 females. the first group was treated at a dose of 2000 mg/kg. Due to the absence of mortality, the second group of animals was also dosed at 2000 mg/kg.

OBSERVATIONS
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality was observed twice daily. Body weights were recorded on day 1 (pre-administration), 8 and 15. Clinical signs were observed at periodic intervals on the day of dosing and once daily thereafter until day 15.
- Necropsy of survivors performed: yes (descriptions of all internal macroscopic abnormalities were recorded).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the animals died during the study.

Clinical signs:

other: No clinical signs were noted.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the oral LD50 value of the test material in female Wistar rats was in excess of 2000 mg/kg bw, the highest permissible dose level tested.

Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF guidelines, following the acute toxic class method.

During the study, the test material was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg bw. All animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15.

None of the animals died during the study and no clinical signs were noted. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Furthermore, no abnormalities were found at macroscopic post mortem

examination of the animals.

Therefore, under the conditions of the study, the oral LD50 value of the test material in female Wistar rats was in excess of 2000 mg/kg bw, the highest permissible dose level tested.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was conducted under GLP conditions and in accordance with standardised guidelines. The study was assigned a Klimisch score of 1. The supporting study is a guideline study but GLP status cannot be confirmed and hence the supporting study has been assigned a Klimisch score of 2. The quality of the database is good.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

3.2 mg/m³ air

Quality of whole database:

The key study was conducted under GLP conditions and in accordance with standardised guidelines. The study was assigned a Klimisch score of 1. The supporting study is a guideline study but GLP status cannot be confirmed and hence the supporting study has been assigned a Klimisch score of 2. The quality of the database is good.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study was conducted under GLP conditions and in accordance with standardised guidelines. The study was assigned a Klimisch score of 1. The supporting study is a guideline study but GLP status cannot be confirmed and hence the supporting study has been assigned a Klimisch score of 2. The quality of the database is good.

Additional information

Acute toxicity oral:

In the key study, the acute oral toxicity of the test material was investigated under GLP conditions and in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF guidelines, following the acute toxic class method.

During the study, the test material was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg bw. All animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15.

None of the animals died during the study and no clinical signs were noted. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Furthermore, no abnormalities were found at macroscopic post mortem examination of the animals.

Therefore, under the conditions of the study, the oral LD50 value of the test material in female Wistar rats was in excess of 2000 mg/kg bw, the highest permissible dose level tested.

This was selected as the study since it was conducted under GLP conditions and in accordance with standardised guidelines.

In the supporting study, the acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 following the standard acute method.

During the study, the test material was administered by oral gavage to four groups of five male Sprague-Dawley rats at dose levels of 1000, 2150, 4640 and 10000 mg/kg bw and to four groups of five female Sprague Dawley rats at dose levels of 2150, 4640, 10000 and 21500 mg/kg bw. All animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice following a 14 day observation period.

All of the females dosed at 2150 mg/kg bw survived; there were 2, 5 and 5 mortalities at dose levels of 4640, 10000 and 21500 mg/kg bw, respectively. All of the males dosed at 1000 and 2150 mg/kg bw survived; there were 4 and 5 mortalities at dose levels of 4640 and 10000 mg/kg bw, respectively. Clinical signs of toxicity such as black mucus, nosebleed, bloody tears were noted in female rats at dosews of 4640, 10000 and 21500 mg/kg and male rats at doses of 4640 and 10000 mg/kg bw. Animals that died during the study were found to have reduced bodyweights compared to those recorded at study initiation. No abnormal necropsy findings occurred in any test animal which could be suspected to be due to the test material.

Therefore, under the conditions of the study, the oral LD50 value of the test material in male and female Sprague-Dawley rats was determined to be 3690 mg/kg bw and 5010 mg/kg bw, respectively.

 

Acute inhalation toxicity:

In the key study, the acute inhalation toxicity of the test material was investigated under GLP conditions and in accordance with the standardised guidelines OECD 403, EU Method B.2, EPA OPPTS 870.1300 and JMAFF.

During the study the test material was administered by nose-only inhalation, for 4 hours, to one group of five male and five female Wistar rats, followed by a 14 -day observation period. Animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice.

The mean actual concentration was 3.2 ± 1.1 mg/L. The nominal concentration was 23.3 mg/L. The generation efficiency was 15%.

The mean mass aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined twice. The MMAD was 3.0 and 3.2 µm, respectively and the GSD was 2.1 and 2.0, respectively.

Under the conditions of the study no mortality occurred and no clinical signs were noted. No effects on body weight and body weight gain indicative of toxicity were noted. Furthermore, no abnormalities were found at macroscopic post mortem examination.

The acute inhalation LC50 of the test material was determined to be in excess of 3.2 mg/L, the highest test concentration considered to be technically attainable.

This was selected as the study since it was conducted under GLP conditions and in accordance with standardised guidelines.

In the supporting study, the acute inhalation toxicity of the test material was investigated in accordance with the standardised guideline OECD 403.

During the study the test material was administered by nose-only inhalation, for 4.5 hours, to one group of five male and five female Sprague-Dawley rats, followed by a 14 -day observation period. Animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice.

The actual concentration was 5153.3 ± 131.1 mg/m³. The mean mass aerodynamic diameter (MMAD) was 5.14 µm, and the GSD was 2.32.

Under the conditions of the study no mortality occurred and no clinical signs were noted. No effects on body weight ndicative of toxicity were noted. Furthermore, no abnormalities were found at macroscopic post mortem examination.

The acute inhalation LC50 of the test material was therefore determined to be in excess of 5000 mg/m³.

Acute dermal toxicity:

In the key study, the acute dermal toxicity of the test material was investigated under GLP conditions and in accordance with the standardised guidelines OECD 402, EU Method B.3 and EPA OPPTS 870.1200.

During the study, five male and five female rats received semi-occlusive dermal applications of 2000 mg/kg bw of test material. The exposure duration was 24 hours. The animals were observed for mortality, clinical signs, body weight changes and local reactions for 14 days after which time they were sacrificed and subjected to gross necropsy.

Under the conditions of the study, none of the animals died, no clinical signs were observed and the body weight development of all male and female animals was within the expected range. Male 21 had a yellow spot on the epididymides. Male 22 had granulated Peyer' patches. These were considered incidental findings and were not considered to be related to treatment with the test material. No specific gross pathological changes were recorded for any other animals. No erythema or oedema was noted on any animal during the study.

It was therefore concluded that the acute dermal LD50 of the test material is in excess of 2000 mg/kg bw.

This was selected as the study since it was conducted under GLP conditions and in accordance with standardised guidelines.

In the supporting study the acute dermal toxicity of the test material was investigated in accordance with the standardised guideline OECD 402.

During the study, five male and five female rats received semi-occlusive dermal applications of 2000 mg/kg bw of test material. The exposure duration was 24 hours. The animals were observed for mortality, clinical signs, body weight changes and local reactions for 14 days after which time they were sacrificed and subjected to gross necropsy.

Under the conditions of the study, none of the animals died, no clinical signs were observed and the body weight development of all male and female animals was within the expected range. No specific gross pathological changes were recorded for any other animals.

It was therefore concluded that the acute dermal LD50 of the test material is in excess of 2000 mg/kg bw.

Justification for classification or non-classification

The substance does not fulfil the classification criteria for acute toxicity according to European Regulation (EC) No 1272/2008.