Aluminium tribenzoate

Endpoint summary

Description of key information

An acute oral toxicity study with rats is available, performed according to OECD/EC test guidelines and GLP principles. The results demonstrate that aluminium tribenzoate has an acute oral LD50 >2000 mg/kg bw. Aluminium tribenzoate was concluded not to have acute inalation toxicity, based on data on substance analogues.

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:

03 January 2017 - 24 January 2017

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008/ including the most recent amendments

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147

Version / remarks:

November 2000, including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Adjustment was made for specific gravity of the vehicle and a correction factor was used to correct for the purity/composition of the test item.

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: 173-204 g
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of daily mean relative humidity occurred. However, laboratory historical data do not indicate an effect of the deviations. Therefore, the study integrity was not adversely affected by the deviation.

IN-LIFE DATES: From: 03 January 2017 to 24 January 2017

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.The test item preparations were stirred on a magnetic stirrer during dosing.
Frequency: single dosage, on day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at Charles River Den Bosch and on test item data supplied by the Sponsor. There was no information available regarding the solubility or stability in vehicle.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The preparations (w/w) were kept at room temperature and were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and/or piloerection were noted for all animals on days 1 and/or 2.

Gross pathology:

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

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw for Aluminium tribenzoate was determined. Based on these results, Aluminium tribenzoate is not classified according to the GHS criteria.

Executive summary:

An acute oral toxicity study was performed with rats, according to OECD/EC guidelines and under GLP principles. Aluminium tribenzoate was administered by oral gavage to two consecutive groups of three female Wistar rats at a single dose of 2000 mg/kg body weight. Observations were made for 15 days after administration. No mortality occurred, hunched posture and/or piloerection were noted for all animals on days 1 and/or 2. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Aluminium tribenzoate in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Aluminium tribenzoate is not classified according to the GHS criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One study available (Klimisch 1).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The rationale to read across the data is included in Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 200 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: See remark

Remarks:

Rats were exposed for 6 hours per day and 5 days per week over a period of 4 weeks.

Mortality:

In the highest dose group, one rat per sex died.

Clinical signs:

other: Not incuded in the evaluation.

Body weight:

The body weight gain was significantly decreased in males and females in the highest dose group compared with controls.

Other findings:

At 25 mg/m3, an increased incidence of interstitial inflammatory cell infiltrate and interstitial fibrosis in the trachea and lungs in treated animals compared with controls was seen. Although the number of these microscopic lesions was higher in treated animals than in controls, there was no clear dose dependency for this effect. A concentration of 250 mg/m3 resulted in upper respiratory tract irritation, as indicated by inflammatory exudate around the nares, and significantly decreased absolute kidney weights in females. In addition, a significant decrease in platelets (males/females), absolute/relative liver weights (males), and trachea/lung weights (females) was noted

Interpretation of results:

GHS criteria not met

Conclusions:

A sub-acute inhalation study with benzoic acid was evaluated by the WHO. In this study, 10 rats/sex/dose were exposed to 0, 25, 250, or 1200 mg benzoic acid dust aerosol/m3 for 6 h per day and 5 days per week over 4 weeks. As only one male and one female died in the highest dose group, it is concluded that the acute LC50 of benzoic acid exceeds 1200 mg/m3. This result is read across to aluminium tribenzoate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The experimental data summarized in this dossier were evaluated by the WHO and therefore considered reliable, although details on experimental set-up are not included in the evaluation.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study was performed with rats, according to OECD/EC guidelines and under GLP principles. Aluminium tribenzoate was administered by oral gavage to two consecutive groups of three female Wistar rats at a single dose of 2000 mg/kg body weight. Observations were made for 15 days after administration. No mortality occurred, hunched posture and/or piloerection were noted for all animals on days 1 and/or 2. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Aluminium tribenzoate in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

A sub-acute inhalation study with benzoic acid was evaluated by the WHO. In this study, 10 rats/sex/dose were exposed to 0, 25, 250, or 1200 mg benzoic acid dust aerosol/m3 for 6 h per day and 5 days per week over 4 weeks. As only one male and one female died in the highest dose group, it is concluded that the acute LC50 of benzoic acid exceeds 1200 mg/m3. This result is read across to aluminium tribenzoate.

Justification for classification or non-classification

Based on the available data, aluminium tribenzoate is not classified for acute oral, dermal or inhalation toxicity according to CLP Regulation (EC) No. 1272/2008.