Triethylaluminium

Endpoint summary

Description of key information

It is recommended that aluminium hydroxide 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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral route:

The available data are adequate to meet the REACH information requirements for aluminium hydroxide with respect to acute oral toxicity. No mortality was established and confirmed among rats after oral administration of aluminium hydroxide at the limit dose 2000 mg/kg bw. According to the results (Aluminium hydroxide, acute oral toxicity study in rats, LABRes, 2009, OECD Test Guideline 423, Klimisch Score 1), the oral LD₅₀(rat) for aluminium hydroxide is above 2000 mg/kg bw.

 

An acute oral toxicity study comparable to OECD 401 was performed with fumed alumina in 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 (Butter, 1969). 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.

 

A study for acute oral toxicity was performed with various aluminium oxide nanoscale samples with particle sizes 30 and 40 nm and bulk sample (50 - 200 µm) in female Wistar rats in a study similar with OECD Test Guideline 420 (Balasubramanyam, 2009).Aluminium oxide nanoparticles with particle size 30 nm and 40 nm and bulk sample with particle size 50 - 200 µm were administered by a single oral gavage to female rats at doses 5, 50, 300 and 2000 mg Al2O3/kg bw. Parameters monitored during this study included mortality and clinical signs of intoxication. There was no mortality related to aluminium oxide oral exposure at any used dose. Under the conditions of this study, acute oral LD50 (rat) of the all type of Al2O3 bulk sample with particle sizes 50 -200 μm and all Al2O3 nano-particles is above 2000 mg/kg bw. 

 

Aluminium oxide (granulated solid product) was tested for acute oral toxicity in female and male rats equivalent to OECD Guideline 401(Nagy, 1979).This study has been performed at the Central Institute for Nutrition and Food Research, Germany. Al2O3 was administered by a single oral gavage to ten males and ten females per group at dose level of 10,000 mg/kg bw after an overnight food withdrawal. Parameters monitored during this study included mortality, clinical signs of possible intoxication, and changes in gross pathology. Clinical observations were performed on all animals during 14 days there the Al2O3 administration. During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to aluminium oxide administration at dose 10000 mg/kg bw. No significant sex differences were noted among animals in the sensitivity to the administered compound. Macroscopic examination at the end of the observation period did not reveal any changes of the internal organs associated with the aluminium treatment.

An acute oral toxicity study comparable to OECD 401 with acceptable restrictions was performed with aluminium oxide (granulated solid product) in both female and male rats (Spanjers, 1979). This study has been performed at the Central Institute for Nutrition and Food Research. Al2O3 was administered by a single oral gavage to ten males and ten females per group at dose level of 10000 mg/kg bw after an overnight food withdrawal. Parameters monitored during this study included mortality, clinical signs of possible intoxication, and changes in gross pathology. Clinical observations were performed on all animals during 14 days there the Al2O3administration. During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to aluminium oxide administration at dose 10000 mg/kg bw. No significant sex differences were noted among animals in the sensitivity to the administered compound. Macroscopic examination at the end of the observation period did not reveal any changes of the internal organs associated with the aluminium treatment.

In addition, an acute oral toxicity study comparable to OECD 401 with acceptable restrictions was performed with Aluminium oxid C (white voluminous powder) in both female and male rats (Spanjers, 1979). This study has been performed at the Central Institute for Nutrition and Food Research. Al2O3 (as Aluminium oxid C) was administered with diet at a ratio of 1: 4 during 24 hours to each male and female (n = 10) at dose level of 10000 mg/kg bw. Parameters monitored during this study included mortality, clinical signs of possible intoxication, behavioural changes, water consumption, stool characteristics, and changes in gross pathology. Clinical observations were performed on all animals during 14 days there the Al2O3 administration. During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to Aluminium oxid C administration at dose 10000 mg/kg bw. Macroscopic examination at the end of the observation period did not reveal any changes of the internal organs associated with the aluminium treatment.

The acute oral toxicity study (limit test) of aluminium hydroxide (SH-20 Muster) in female CRL (WI)BR rats was assessed in a study performed equivalent to OECD 423 (Spanjers, 2009).This study has been performed in accordance with the OECD 423 (17thDecember 2001), Commission Regulation (EC) No 440/2008, B.1 tris (L 142, 30 May 2008), OPPTS 870.1100 (EPA 712-C-98-190, August 1998) and the Principles of Good Laboratory Practice (Hungarian GLP Regulations: 9/2001.III. 30). Aluminium hydroxide was administered by a single oral gavage to animals after an overnight food withdrawal at a concentration of 2000 mg/mL in vehicle (PEG 400) with a treatment volume of 10 mL/kg bw. Parameters monitored during this study included mortality, clinical signs, body weight and body weight gain. Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on days 1, 0 and 7 and before necropsy. Necropsy was performed on all animals on Day 14. During the 14 days of the observation period, there was no mortality or clinical signs of intoxication related to aluminium hydroxide administration at 2000 mg/kg bw. Soft faeces were recorded in all treated animals at first day of administration. It was no differences in body weight gains between aluminium treated and control animals. 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 aluminium hydroxide/SH-20 Muster was above 2000 mg/kg bw in female CRL:(WI)BR rats.

Prabhakar et al. (2011) investigated the acute oral toxicity of bulk Al oxide powder (purity 90% and 50 - 200 µm, as reported by Balasubramanyam et al., 2009) and two nanoscale aluminium oxide samples (Al2O 330 nm and Al2O 340 nm, purity > 90%) in fasted female Wistar rats (8 - 10 weeks old, 10 animals per group) given a single dose of 500, 1000 and 2000 mg Al2O3/kg bw by gavage. Control groups (10 animals per group) received the equal volume of 1% Tween-80. The samples for administration were prepared as suspended solutions in 1% aqueous Tween 80 and dispersed by ultrasonic vibration for 10 min. Animals were treated with 1 mL of dosing solution per 100 g body weight (as described in Balasubramanyam et al., 2009). All of the animals were kept under controlled housing and environmental conditions and were fed a commercial pellet diet and drinking water ad libitum. All procedures were conducted in accordance with Institutional (National) Animal Care guidelines.

No clinical signs of intoxication or deaths were observed during 14 days of the observation period and no statistically significant changes in body weight, food intake or organ weight were found (data not shown). On day 3 after exposure, bulk Al oxide powder-treated rats showed a statistically significant decrease in the reduced gluthatione (GSH) content in the brain, liver and kidney compared to the 1% Tween 80-treated controls. In the liver, acute oral exposure to bulk Al oxide powder was associated with statistically significant reductions in superoxide dismutase (SOD) (1000 and 2000 mg/kg) and glutathione reductase (GR) activity (1000 and 2000 mg/kg) and increased catalase (500, 1000 and 2000 mg/kg) and gluthatione S-transferase (GST) activity (2000 mg/kg); in the kidney there was a statistically significant increase in malondialdehyde (MDA) levels, decreased glutathione reductase activity (2000 mg/kg, respectively) and increased catalase and GST activities (2000 mg/kg, respectively ) compared to the controls. No statistically significant changes in these parameters in the bulk Al oxide powder-treated rats were found on day 14 after exposure. No changes in the oxidative stress biomarkers were observed in the heart of the bulk Al oxide powder-treated animals at either time interval. On day 14, the brain, liver, kidney and heart of the bulk Al oxide powder-treated and control animals were subjected to histopathological examination; no histological changes in the liver, brain, heart or kidney were observed. Treatment of animals with nanoscale Al oxide particles induced a more pronounced response in the studied biochemical outcomes compared to the bulk Al oxide powder-treated animals. Both nanoscale samples changed oxidative stress biomarkers in a dose-dependent manner, in comparison to no response after oral dosing with the bulk Al oxide powder. Significant hepatic changes were observed in rats treated with 2000 mg Al2O3 (30 and 40 nm)/kg bw and these included dilated central vein, hepatic artery, hepatic portal vein and bile tract. The lack of mortality precluded estimation of an oral LD50 value. The authors suggested that, under the conducted experimental conditions, the acute oral median lethal dose (LD50) of a bulk Al oxide powder and the nanoscale Al2O3 samples (30 and 40 nm) was greater than 2000 mg Al2O3/kg bw in female rats. There were no evident clinical signs of intoxication related to oral exposure to aluminium at 500, 1000 or 2000 mg/kg bw. Only limited details were available on physical and chemical characteristics of the Al oxide bulk form and nanoparticles, lack of a control group (treated with drinking water), few details regarding preparation of dosing solutions and analytical verification of administered dose and the terms of the conducted observations and examinations were not provided. Relatively limited numbers of animals (n = 5) were used in the biochemical assays and histopathological examinations, no control group available for a second time interval (at 14 days of the study) and only a limited number of toxicological endpoints were studied. The results contribute to the evidence of low acute oral toxicity (e.g., mortality) of Al oxide independent of the particle size. However, methodological deficiencies and insufficient description of purities and particle sizes decrease the confidence in the reported results and reduce the utility of the findings for risk assessment. Based on the overall study design and noted limitations, a Klimisch Score of 3 is considered appropriate.

 

Rawy et al. (2012) reported on the acute oral toxicity and toxicokinetic parameters [e.g., the maximum concentration (Cmax), maximum time to peak concentration (Tmax, days), the elimination rate constant (Lz, day 1), the elimination half-life time (t1/2,day), mean residence time (MRT, day) and clearance (Cl, L/day)] of Al in the liver, kidney, brain, intestine (µg/g wet wt.) and serum (µg/ml)] after a single oral dose of Al chloride hexahydrate (AlCl3•6H2O) in adult albino rats (120 ± 20 g., 5 animals per group). To estimate an oral LD50, the rats received a single dose of 0.5, 1.25, 2.5, 3.5 or 4 g AlCl3/kg bw by gavage. Mortality in each group was recorded through 24 hr post-exposure. The LD50 was calculated as 3.5 g AlCl3/kg bw (no other details available). This study has a number of the limitations: no details were available on type of vehicle used to prepare the AlCl3 solutions. The LD50 was estimated based on a 24 hr post-exposure observation instead of the standard 14 days. The authors expressed the LD50 value in mg AlCl3 and did not convert the value to mg Al/kg bw to facilitate comparison to the acute oral LD50 in rats (370 mg Al/kg bw) for AlCl3•6H2O reported by Llobet et al. (1987). Comparing the Llobet et al. (1987) oral LD50 as elemental Al to that reported by Rawy et al. (2012) (707 mg Al/kg bw) shows that the more recent value is about one-half as potent as that reported previously. As such, it is not clear whether this marked difference is due to the abbreviated post-exposure observation period used by Rawy et al. (2012) or to other factors. Due to these limitations, the reported results should be interpreted with caution and a Klimisch Score of 3 was assigned. The results are of only limited utility for human health risk assessment.

 

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

 

Dermal route:

In a human dermal absorption study, Flarend et al. (2001) showed minimal absorption of aluminium 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:

Human Studies

No epidemiological studies were identified that examined acute irritative effects, for example cross-shift lung function changes or respiratory symptoms, on inhalation exposure to aluminium metal dust or powder.  

 

Animal Studies

Thomson et al. (1986) conducted a study in male Fischer 344 rats (10 - 12 weeks old) to investigate and compare the acute inhalation toxicity of aluminium flake and brass flake dusts. Both were irregularly shaped flake dusts coated with <2% palmitic and stearic acids to facilitate the milling process in manufacture. Two experiments were conducted: one with observations at 24 hours and 14 days post-exposure, the other with additional groups observed at 3 and 6 months post-exposure, in order to examine longer term effects of the acute exposure. The animals were exposed to the dust for 4 hours. During the exposure period, the animals were placed in compartmentalized wire cages without food, water or bedding in temperature - (22 ºC ± 2 ºC) and humidity - (30 to 70%) controlled chambers. The test atmospheres were produced using a Metronics Model #3 aerosol generator. Nominal concentrations for the aluminium powder were 10, 50, 100, 200 and 1000 mg/m³. The corresponding concentrations determined gravimetrically were 9.16, 47.3, 111, 206 and 888 mg/m³. The MMAD for the aluminium powder was 1.58 µm (geometric mean diameter from microscopic analysis = 2.82 ± 0.26 µm). All animals were examined for toxic signs before and after exposure and daily during the post-exposure period. The animals were weighed at weekly intervals during the experimental and post-exposure periods. Pulmonary function measurements were conducted at 24 hours, 14 days, 3 months and 6 months post-exposure. Bronchopulmonary lavage was conducted and the BALF analysed for total cell counts, differential cell counts, and biochemical parameters (total protein and levels of glucose-6-phosphate dehydrogenase (G-6-PD), lactate dehydrogenase (LDH), and alkaline phosphatase (ALKP)). Blood samples were also collected by cardiac puncture at each timepoint post-exposure for the analysis of copper, zinc, and aluminium.  After blood collection, rats were necropsied and the following examinations performed: total body weight, organ weight (heart, lung, kidneys, gonads), gross and microscopic pathology of nasal air passages, trachea, lungs and hilar lymph nodes. No mortality was observed even at the highest aluminium flake concentration. No toxic signs were observed and there were no changes in measurements of lung function even at the highest dose (1000 mg/m³).  At concentrations greater than 10 mg/m³, an increase in polymorphonuclear neutrophils in the bronchoalveolar lavage was observed at 24 hours, typical of a mild acute inflammatory response. Increases in lactate dehydrogenase, alkaline phosphatase and total protein that persisted to 3 months provide evidence for a chronic irritant response in the presence of insoluble aluminium flakes retained in the lungs. These changes were not observed at the lowest dose level, 10 mg/m³. Multifocal microgranulomas were observed in terminal airways and alveolar septae in the 200 and 1000 mg/m³ dose groups at 14 days, 3 months and 6 months. Black particulate material was observed in the hilar lymph nodes at 14 days and also later timepoints suggesting clearance by alveolar macrophages. The acute inflammatory response to aluminium flakes was less dramatic than those for more soluble brass dust. The brass dust, however, did not exhibit evidence of a chronic irritant response, effects were resolved by 14 days post-exposure with the exception of larger numbers of alveolar macrophages around terminal airways which had resolved by 3 months. Brass particulate matter was not found in the lavage fluid or in histopathological examinations. The 4 hour exposure period conforms with acute inhalation toxicity guidelines. The use of only one sex of animals and the dose levels were adequately justified. Concentrations were analytically verified and sufficient numbers of animals were used. The results from lung function measurements were not provided in the publication and the highest dose was not intended to allow estimation of the LC50. Therefore, the LC50 is greater than 888 mg/m³.

 

Stillmeadow Inc. (1990) conducted a GLP-compliant acute toxicity inhalation study in rats for Vista Chemical Company using Vista Catapal Alumina. The objective of this study was to determine the acute inhalation irritation potential of the Catapal Alumina Fines (fine powder, MMAD: 4.64 microns (geometric standard deviation - 3.16 microns)) (LOT 2169 V3612B). Ten male and ten female rats were exposed for 4 h to an aerosol generated from the undiluted test material (fine powder) at a concentration of 5.09 mg/L (equivalent to 5,090 mg/m³). During exposure Al- treated and control groups were placed in individual, stainless steel cages within a 500 L stainless steel, New York University design, dynamic flow inhalation chamber. Twenty rats (negative control group) were housed in the same manner in an identical inhalation chamber for 4 h without exposure to the test material. All animals were returned to their laboratory cages within 24 h after termination of exposure. The aerosol was generated by using a Gem T Trost Air Mill coupled with a motor driven revolving disc delivery system and then combined with filtered air and drawn into the exposure chamber. Air flow into the chamber was maintained through the use of a calibrated critical orifice. Air flow was monitored at 30 min intervals during exposure and it was sufficient to keep adequate oxygen content of the exposure atmosphere. Temperature and humidity were monitored at 30 min intervals during exposure using a Taylor wet bulb/dry bulb hydrometer located in the exposure chamber. The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour. The nominal concentration was determined by dividing the loss in weight of the test material after the exposure by the total volume of air passed through the chamber. Particle size determinations were performed using an Andersen cascade impactor. The exposure concentration determined gravimetrically was confirmed as 5.09 mg/L. The mass median aerodynamic diameter (MMAD) of the Catapal Alumina fine powder particles (administered undiluted as an aerosol) was 4.64 microns (geometric standard deviation - 3.16 microns) (4 hr distribution data). Clinical observations were performed on all animals daily, before and after exposure. The animals were weighed before study and at 24, 48 and 72 h post-exposure. The general appearance of Al-treated and control animals, clinical signs and time of death (if occurred) were recorded at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 24 h and at 2 and 3 days post-exposure. To evaluate pulmonary changes over time, some animals were sacrificed at one or at 3 days after the termination of exposure. The gross necropsy examination was conducted on each of the Al-treated and control animals (5/5 males and 5/5 females were randomly selected from Al treated and control groups) at 24 and 72 h after exposure, respectively. Nasal turbinates, lungs and trachea from all Al-exposed and control animals were removed and fixed in 10% neutral buffered formalin for microscopic examination.

No mortality was observed in male or female rats following acute inhalation exposure to undiluted test material as an aerosol at 5.09 mg/L for 4 h during 3 days of the post-exposure observation period. Clinical signs (piloerection) were noted in male and female rats during exposure and in all males and females at 1.5 and 2.0 h post-exposure, respectively. Decreased physical activity was observed in the treated male and female rats during exposure and at 1.0 and 1.5 h post- administration, respectively. Ptosis was observed in the treated male and female rats during the exposure period only. All animals appeared to be normal and no abnormal signs were observed at 24, 48 and 72 h post-administration and no changes in body weights were noted during the post-exposure observation period. Macroscopic examination at the end of the 24 and 72 h observation periods did not reveal any treatment -related changes of the internal organs compared to the control. There were no histopathological changes in the nasal turbinates, trachea and lungs of the Catapal Alumina exposed animals. The use of both sexes revealed no significant differences in gender sensitivity. Because no mortality was observed in either Al-treated male or female rats, the results do not allow estimating the LC50. The authors suggested that the acute inhalation LC50 for Catapal Alumina Fines is greater than 5.09 mg/L (5,090 mg/m³).

Overall, this GLP compliant study was well-reported and it was well-conducted. The main goal of the study was to determine the acute inhalation irritation potential of the Catapal Alumina Fines. Although no regulatory guideline was mentioned explicitly, the study appears to have been conducted to conform generally to guidance criteria on acute inhalation toxicity testing (OECD TG 39, OECD TG 436 and OECD TG 403). The 4 h exposure period conforms to acute inhalation toxicity guidelines and sufficient numbers of animals of both sexes were used. Chamber atmosphere samples were taken from the vicinity of the animals’ breathing zone. The airflow was monitored at regular intervals to detect possible changes in the exposure concentrations. Deviation of the individual chamber concentration samples from the mean chamber concentration did not exceed 20%. In addition, the mass concentration obtained by particle size analysis was within reasonable limits of the mass concentration obtained by filter analyses which suggests that were no considerable sampling errors. Concentrations were gravimetrically verified. Clinical signs observed in all male and female rats during exposure period were short-term and reversible and included decreased activity, piloerection and ptosis. These clinical signs were not observed in Al -exposed male and female rats at 24, 48 or 72 h after the termination of the exposure. No signs of respiratory irritation were observed in male or female rats following an acute inhalation of Catapal Alumina Fines at 5.09 mg/L (5090 mg/m³). The authors suggested that the acute inhalation LC50 for Catapal Alumina Fines was greater than 5.09 mg/L when administered undiluted as aerosol to albino rats. However, some caution is required in interpreting results given the short post-exposure observation (3 days instead of 14 days) period. Based on the overall study design and limitations, a Klimisch Score of 2 (reliable with restrictions) is appropriate for this study.

 

The objective of the pre-guideline acute inhalation toxicity study conducted by Laboratories (Cabot, 1969) was “to determine the acute inhalation toxicity and calculate the LC50, the confidence limits and slope function of the test material.”  Male rats (age unspecified) were exposed for one hour to concentrations of 0, 5.06, 5.88, 6.28 and 8.22 mg of aluminium oxide (fumed alumina) per litre of air in inhalation chambers. The authors state that 8.22 mg/L was the highest concentration obtainable under the experimental conditions. The mean weight of each experimental group was reported (201 g for the negative control and 203 g, 195 g, 200 g and 200 g for the treatment groups, ordered with increasing dose). Individual weights were not provided. Limited detail was provided on the production of the test atmosphere. Briefly, the compound was aerosolized and delivered into a 100 litre exposure chamber. The concentrations of test material were analytically verified by drawing known volumes of chamber atmosphere across weighed filters. The filters were then re-weighed and the average concentration of the test compound calculated on the basis of the volume and the gravimetric measurement. After the one hour exposure period, the animals were removed from the chamber and observed for 14 days. After this time, they were killed and necropsy was performed. Mortality and clinical signs appear to have been monitored daily post-exposure. During the one-hour exposure period, observation appears to have been continuous. The trachea, lungs, liver and kidneys were examined for gross pathological changes. Body weights were determined at the start and termination of the experiment. The LC50, 95% CI and slope (S) were estimated from the data using the graphical log-probit method of Litchfield and Wilcoxon (1949) (J Pharmacol Exp Ther 96: 99). Mortality was observed at the highest three dose levels, reaching 50% in the group exposed to the highest levels (8.22 mg/L). Deaths occurred either during or shortly after exposure.  The clinical symptoms observed were consistent with respiratory distress. The surviving animals were described as showing only “slight” toxic effects and good recovery by the end of the 14 day observation period. The authors report only a slight effect on weight gain. The statistical or biological significance of the difference was not mentioned. A greater amount of discolouration was observed on the surface of lungs of treated animals compared with control animals. A “slight” increase in the number of lesions on the lungs of the test animals was also reported – although individual data or further detailed was not provided. Animals that died were found to have a white gel in their trachea and stomachs. Their stomachs were also gas-filled and enlarged. The liver and kidney showed no difference between the treated and control animals on macroscopic examination. The authors of the study suggest that the deaths were likely due to suffocation from blockage of air passages by gel formed from the test substance in the high humidity of the air passages.  The LC50 estimated from this study based on one hour of exposure was 7.6 mg/L (95% CI: 6.45 – 8.95 mg/L). This study report lacked some detail on the test substance (information obtained from sponsor), the chamber conditions and animal husbandry, and also the results from the examination of the gross pathology of the trachea, lungs, kidney and liver. The duration of exposure was only one hour. The number of animals and the reporting of the results that were included were adequate. 

 

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 2.58µm 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 °C) 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. A Klimisch Score of 2 (reliable with restrictions) is considered appropriate.

 

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

 

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.