Barium bis(dihydrogenorthophosphate)

Endpoint summary

Description of key information

Oral (OECD 423, RL1), rat: LD50 > 300 < 2000 mg/kg bw, LD50 cut-off = 2000 mg/kg bw

Dermal (OECD 402, RL1), rat: LD50 > 2000 mg/kg bw (limit test)

Inhalation: no data available

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Behörde für Gesundheit und Verbraucherschutz, Hamburg, Germany

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 173 - 194 g
- Fasting period before study: approx. 16 hours before administration
- Housing: groups of three in MAKROLON cages (type III plus)
- Diet: ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: hydroxypropyl methylcellulose

Details on oral exposure:

VEHICLE
0.8% aqueous hydroxypropyl methylcellulose

MAXIMUM DOSE VOLUME APPLIED: 1.3 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: according to the OECD/EC guidelines

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw: 1/3 in the first step and 2/3 in the second step
300 mg/kg bw: no animal died prematuraly

Clinical signs:

2000 mg/kg bw: slightly to moderately reduced motility, slight to moderate ataxia and slightly to moderately reduced muscle tone in 4 of 6 animals, pilo-erection in all 6 animals and slight dyspnoea in 3 of 6 animals; In addition, pulpy faeces with offensive smell was observed in 2 of 6 animals and a reddish-brown wetted lower jar was noted in 1 of 6 animals.
300 mg/kg bw: no clinical signs observed

Body weight:

All surviving animals gained the expected weight at the end of the study period.

Gross pathology:

No pathological changes were observed at necropsy.

Interpretation of results:

other: Category 4 based on CLP criteria (EU GHS criteria according to Regulation (EC) No. 1272/2008)

Conclusions:

Under the present test conditions a LD50 value for Barium bis(dihydrogenorthophosphate between 300 and 2000 mg/kg bw was observed. According to OECD Guideline 423 Annex 2d a LD50 cut off = 2000 mg/kg bw was estimated. Therefore, CLP criteria for Category 4 according to Regulation (EC) No. 1272/2008 are met.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01. November 2016 - 30. January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Behörde für Gesundheit und Verbraucherschutz, Hamburg, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Sulzfeld, Germany
- Age at study initiation: males: approx. 8 weeks; females: approx. 9 weeks
- Weight at study initiation: males: 231 - 250 g; females: 230 - 250 g
- Fasting period before study: no
- Housing: singly in MAKROLON cages (type III plus)
- Diet: ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

DMSO

Details on dermal exposure:

TEST SITE
- Area of exposure: back between the fore and hind extremities
- % coverage: 5 cm x 6 cm, approx. 1/10 of body surface
- Type of wrap if used: The test substance was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips on the application site.

REMOVAL OF TEST SUBSTANCE
- Washing: not specified

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not specified
- Concentration: 10 g test substance was moistened in 5 g DMSO
- Constant volume or concentration used: not specified
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: Changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern, were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

no signs of toxicity observed

Body weight:

expected body weight gain

Gross pathology:

no abnormalities observed

Other findings:

- Skin reaction: none

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under these test conditions the test substance showed no acute dermal toxicity with a LD50 > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral:

The acute oral toxicity of the test substance was assessed in a study performed according to OECD Guideline 423 and in compliance with GLP (LPT, 2017). A group of three fasted female CRL:CD(SD) rats was treated with the test material at a dose level of 2000 mg/kg bw. The test material was administered by gavage formulated in 0.8% aqueous hydroxypropyl methylcellulose at a dosing volume of 1.3 mL/kg bw. The animals were observed for 14 days and body weights were measured. All animals were subjected to a necropsy and a macroscopic examination. In this first step 1 of 3 female rats died. After treatment of 3 additional rats with 2000 mg/kg bw test substance in a second step 2 of 3 rats died. After treating 3 further female rats with 300 mg/kg bw no mortality was observed and a confirmatory group of three fasted females was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to OECD Guideline 423. Treatment with the test substance at 2000 mg/kg bw revealed slightly to moderately reduced motility, slight to moderate ataxia and slightly to moderately reduced muscle tone in 4 of 6 animals, pilo-erection in all 6 animals and slight dyspnoea in 3 of 6 animals. In addition, pulpy faeces with offensive smell were observed in 2 of 6 animals and a reddish-brown wetted lower jar was noted in 1 of 6 animals. Oral administration of 300 mg/kg bw test substance did not reveal any changes. No abnormalities were noted at necropsy at dose levels of 2000 and 300  mg/kg bw. All surviving animals gained the expected weight at the end of the study period. Thus, under the conditions of this study, the acute oral LD50 value of the test substance was found to be between 300 and 2000 mg/kg bw in female rats. The LD50 cut-off value according to OECD 423 guideline is 2000 mg/kg bw.

Dermal:

The acute dermal toxicity of the test substance was assessed in a study performed according to OECD Guideline 402 and in compliance with GLP (LPT, 2017). Five male and five female CRL:CD(SD) rats were treated with the test substance by a single occlusive dermal application at 2000 mg/kg bw (limit test). The animals were observed for 14 days and body weights were measured. All animals were subjected to a necropsy and a macroscopic examination. Furthermore skin irritation scores were evaluated during the observation period. No mortality occurred and no clinical signs or local dermal signs were observed. There were no treatment related effects on body weight or body weight gain. There was no evidence of any observations at a dose level of 2000 mg/kg bw at necropsy. Thus, under the conditions of this study, the acute dermal LD50 value of the test substance was found to be > 2000 mg/kg bw in male and female CRL:CD(SD) rats.

Inhalation:

An acute inhalation toxicitiy study is technically not feasible due to the hygroscopic properties of the test substance. Furthermore, because of the harmonised classification for Barium compounds, the test substance is classified for acute inhalation toxicity (Cat. 4).

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification according to Regulation (EC) 1272/2008, and is therefore classified as acute toxic Category 4 (H302).

The available data on acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

A harmonised classification for Barium compounds are available, therefore the test substance is classified for acute inhalation toxicity (Cat. 4, H332).