Barium m-toluate

Endpoint summary

Description of key information

Acute oral toxicity (OECD 423, GLP): LD50 value: 300 < LD50 ≤ 2000 mg/ kg bw

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:

2017-11-27 to 2017-12-20

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:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2015-06-05

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: dry, < 30°C

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 9-10 weeks
- Weight at study initiation: 165 - 184 g
- Fasting period before study: prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: animals were kept in groups of three in IVC cages, type III H, polysulphone cages; bedding material: Altromin saw fibre bedding
- Diet (ad libitum, for exception refer to "fasting period before study" above): Altromin 1324 maintenance diet for rats and mice (Altromin Spezialfutter GmbH & Co. KG, Im Seelenkamp 20, 32791 Lage, Germany)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C
- Relative humidity: 55 % ± 10%
- Air changes: 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Source: Sigma-Aldrich Chemie GmbH, Riedstrasse 2, 89555 Steinheim, Germany
- Justification for choice of vehicle: this vehicle was chosen due to its non-toxic characteristics
- Lot no.: MKCC0462
- Expiry date: 2018-01-31

Doses:

Starting dose (step 1): 300 mg/kg bw
Step 2: 2000 mg/kg bw
Step 3: 300 mg/kg bw

No. of animals per sex per dose:

9 female rats (3 animals/step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: a clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. The animals which died spontaneously during the observation period were necropsied as soon as they were killed.

Statistics:

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

Preliminary study:

not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg /kg bw: no animals died
2000 mg/kg bw: all animals died prematurely

Clinical signs:

other: 300 mg/kg bw after 0-30 min: slightly reduced spontaneous activity, hunched posture, slight/moderate piloerection, prone position after 30-60 min: moderately reduced spontaneous activity, hunched posture, moderate piloerection, prone position, sunken flun

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 value: 300 < LD50 ≤ 2000 mg/ kg bw
According to the Regulation (EC) NO 1272/2008 and subsequent adaptations, the substance is classified as acute toxic via the oral route (Cat.4; H302).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

key study available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Barium m-toluate

One acute toxicity study in rats (key study) via the oral route with barium m-toluate is available, resulting in a LD50 in the range of 300 to 2000 mg/kg bw.

Barium m-toluate was administered in three steps at doses of 300 and 2000 mg/kg bw to female Wistar Crl:WI (Han) rats. All animals were observed daily for a period of 14 days. Individual body weights were recorded before administration and thereafter in weekly intervals. At the end of the study all animals were sacrificed, dissected and inspected macroscopically. At 300 mg/kg bw no mortality and changes in body weight or pathological changes were observed. At 2000 mg/kg bw all animals died prematurely. The LD50 results in a classification of the barium m-toluate for acute toxicity via the oral route Category 4 and is in line with the legally binding harmonised classification of barium salts ((EC) No 1272/2008; Index No. 056-002-00-7). The read-across to data of the barium chloride dossier (assessment entity barium cations), which was itself classified as acute toxic via the oral route Category 3 thus represents an overly conservative approach for read-across.

The acute oral toxicity study was conducted as a bridging study for systemic effects displaying the applicability to read-across to the assessment entities barium cations and m-toluic acid anions (for a detailed description of the read-across approach please refer to the separate report attached to section 13).

In the assessment of the systemic toxicity of barium m-toluate, a read-across to data for m-toluic acid and soluble barium substances is applied since only the ions of barium and m-toluate are systemically available and determine the toxicological potential of barium m-toluate.

 

Signs of acute dermal toxicity are not expected for barium m-toluate, since the two moieties barium and m-toluic acid have not shown signs of acute dermal toxicity in experimental testing (LD50 > 2000mg/kg). Under the assumption that the moieties of barium m-toluate show their toxicological profile individually upon dissolution, the acute dermal toxicity of barium m-toluate can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

A study for acute toxicity via inhalation was not conducted with barium m-toluate, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the assessment entities, please refer to the relevant sections in the IUCLID and CSR.

Barium

Acute oral toxicity

There are three reliable studies for acute oral toxicity testing (Müller, 1983, Borzelleca, 1988 and Tardiff, 1980). All studies were used in a weight of evidence approach. The study performed by Müller, 1983 results in an LD50of 645 mg BaCl2/kg bw (male/female), the study performed by Borzelleca in 1988 leads to an LD50>100 and <300 mg/kg bw. whereas the study conducted by Tardiff 1980 results in an LD50of 300 mg/kg bw.

 

Acute dermal toxicity

According to the SIAR 27 prepared for barium dichloride, an acute dermal toxicity study on barium dichloride was conducted according to OECD 402, in compliance with GLP. In this study, the dermal LD50 was greater than 2000 mg BaCl2/kg bw in rats. Nevertheless, primary data could not be made available by the registrant.

 

m-toluate

Acute oral toxicity

One acute toxicity study in rats (key study) via the oral route with m-toluic acid is available, resulting in LD50 (oral, male and females rats) > 2000 mg/kg bw

According to the EC-Regulation 1272/2008 and subsequent regulations, m-toluic acid is not classified as acute toxic via the oral route.

 

Acute dermal toxicity

The acute oral toxicity study with m-toluic acid did not show any signs of systemic toxicity upon administration up to the limit dose, indicating a very low systemic toxicity of that substance. The low systemic toxicity is corroborated by supporting evidence in an in vivo study, in which 6 japanese white rabbits were dermally exposed to the substance for 24 hours with a 7 day observation period. No mortality or other clinical signs of systemic toxicity were observed in animals. In accordance with Annex XI, Section 1.2 further testing is considered not to be required, since the overall weight of evidence in experimental animals exposed via dermal and oral route did not indicate any acute toxic effects. Experimental testing is therefore waived.

Justification for classification or non-classification

The LD50 for barium m-toluate is 300 < LD50 ≤ 2000 mg/ kg bw, hence the substance is classified as acute toxic via the oral route Category 4 (H302) in accordance to Regulation (EC) 1272/2008 and subsequent adaptations.

The calculated dermal LD50 for barium m-toluate is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008and subsequent adaptationsfor acute dermal toxicity.

Barium m-toluate is a barium salt and thereforeclassified as acute toxic via the inhalative route Category 4 (H332) according to Annex VI, Index No. 056-002-00-7 of Regulation (EC) 1272/2008.