Boric acid, aluminum salt

Endpoint summary

Description of key information

Read-across from supporting studies with Aluminum oxide as surrogate (Al2O3 is the main part of Aluminum borate) leads to conclusions as follows:
It is recommended that aluminium oxide is not to be classified for acute oral, dermal and inhalation toxicity.
Oral LD50 (rat) > 2000 mg/kg bw
Inhalation LC50 (rat) >  2.3 mg/L

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: lack of details on test substance, no data available about the control group, no details available on the preparation of dosing solution and physical form of the administered compound.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (no further information)
- Age at study initiation: No data available.
- Weight at study initiation: 183-299 grams (males) and 158-204 grams (females).
- Fasting period before study: Animals were fasted overnight prior to treatment.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No details available.

Doses:

1000, 1590, 2510, 3980, 6310, 10000, and 15900 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

Duration of observation period following administration: 14 days.
Frequency of observation in all animals: immediately after dosing, 1, 4 and 24 hours after dosing, and one daily during the total of 14 days observation period.
At the end of study, gross necroscopy was performed on all animals (animals which died during the study and on those sacrificed by chloroform overdose).

Statistics:

No data available.

Preliminary study:

Not performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 900 mg/kg bw

Based on:

test mat.

Mortality:

The fumed alumina did not cause mortality in males and females Sprague-Dawley rats after an acute oral exposure (gavage) to 1000, 1590, 2510, 3980, 6310, 10000 and 15900 mg/kg bw.

Clinical signs:

other: No toxic effects were noted in aluminium treated animals at doses from 1000 mg/kg to 10000 mg/kg. At dose 15900 mg/kg, clinical signs of depression, laboured respiration, and piloerection (males) were noted immediately after administration of the compou

Gross pathology:

No changes in gross pathology were noted at sacrifice.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for acute oral toxicity, no classification is required.

Executive summary:

An acute oral toxicity study comparable to OECD 401 was performed withfumed aluminain female and male rats. This study has been performed at the Hazelton Laboratories, Inc.. Fumed alumina was administered by a single oral gavage to seven groups of five males and five females per group at dose levels of 1000, 1590, 2510, 3980, 6310, 10000 and 15900 mg/kg bw after an overnight food withdrawal.

Parameters monitored during this study included mortality and clinical signs of possible intoxication.Clinical observations were performed on all animals immediately after dosing, at 1, 4 and 24 hours after dosing and daily for 14 days thereafter.

During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to aluminium oxide administration at dose range from 1000 mg/kg to 10000 mg/kg bw. 

Clinical signs of depression, laboured respiration, and piloerection (males) were noted immediately and hunched appearance was noted at 24 hours post-administration of the highest dose 15900 mg/kg. 

No significant sex differences were noted among animals in the sensitivity to the administered compound or during the recovery period. Animals appeared normal by day 7 (females) and day 8 (males).

Macroscopic examination at the end of the observation period did not reveal any aluminium-related changes of the internal organs of the aluminium treated animals compared to the control group.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the fumed alumina is above 15900 mg/kg bw in both females and males rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Value:

mg/m³ air

Additional information

Oral route:

The available data are adequate to meet the REACH information requirements for aluminium oxide with respect to acute toxicity. According to the reported results (acute oral toxicity study, Hazleton Laboratories, USA 1969; Central Institute for Nutrition and Food Research, Germany 1979a; Central Institute for Nutrition and Food Research, Germany 1979b, Central Institute for Nutrition and Food Research, Germany 1979c; IUCLID, Aluminium Oxide Dataset, 2000; and Balasubramanyam et al., 2009b and Balasubramanyam et al., 2009a), the oral LD₅₀for aluminium oxide is above 2000 mg/kg bw in both female and male rats.

 

Based on the available data, it is proposed that aluminium oxide need not be classified for acute oral toxicity.

Dermal route:

In a human dermal absorption study, Flarend et al. (2001) showed, that aluminium is absorbed into the systemic circulation on single application with occlusion of aluminium chlorohydrate to underarms. Based on urine measurements, 0.01% of the applied aluminium was absorbed showing that aluminium does not cross the dermal barrier effectively. Thus, a dermal study is not necessary.

Inhalation route:

Animal Studies

The study by Cabot (1996) was conducted according to EPA Guidelines for Test Procedures Subdivision F, Series 81-3 and TSCA 40 CFR 798.1150. Five healthy male and five healthy female Wistar Albino rats were exposed to fumed alumina in an inhalation chamber for 4 hours. The number of animals used and the exposure duration were adequate according to the guidelines. The air concentration in the chamber, determined gravimetrically, was 2.3 mg/L.  Only one concentration was tested. The average mass median diameter was 2.58 µm with a geometric standard deviation of 3.10 µm (2.31 µm, GSD 2.97 in the first 30 second sampling period and 2.85 µm, GSD 3.22 in a second sampling period). Chamber airflow, temperature (20.7 – 23.3 ºC) and humidity (60 to 61%) were monitored throughout the exposure period. Animals were observed for signs of toxicity at approximately one hour intervals during exposure, at one hour post exposure and then daily during a 14 day exposure period. Body weights were recorded pre-test, weekly and at termination.  No deaths were observed during exposure or during the 14 day post-exposure period. All animals had closed eyes, wet nose/mouth areas and fur coated with the test materials during the exposure. Observations were normal during the 14-day post-exposure period. Weight gain was normal in all the male animals. Weight loss was observed in two females on day 7 of the post-exposure period and in another two females on day 14. Lungs that were darker than normal with red areas were observed in only one female on necropsy. Based on the results of this study, the LC₅₀ is greater than 2.3 mg/L. The main limitations of this study were the lack of description of the test materials and the use of only one concentration with no rationale provided for the level chosen. 

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for acute toxicity, no classification is warranted.