ALFERROCK

Endpoint summary

Description of key information

No information related to acute toxicity of the target substance is available. However, data are available from the read-across analogue substances aluminium and aluminium chloride, which were used in a weight-of evidence approach. Details on the read-across rationale are provided in section 13.

In an acute oral toxicity study, young adult Wistar rats were orally exposed to the highly soluble aluminium chloride. The oral LD50 was considered to be 3470 mg/kg bw and 3450 mg/kg bw, in female and male rats, respectively.

In an acute inhalation study rats were exposed up to a concentration of 1000 mg/m³ of aluminium powder for four hours. No mortality was observed during a 6 months post-exposure period. Thus, the LC50 can be considered to be greater than 1000 mg/m³.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

3 470 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

3 450 mg/kg bw

Based on:

test mat.

Mortality:

Mortality occured, but no detailed information was provided, except the LD50 value for male and female rats

Clinical signs:

other: Hematuria and bloody stool

Gross pathology:

congestion of stomach and brain

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity test the LD50 in Wistar rats after treatment with aluminium chloride was 3450 mg/kg bw for males and 3470 mg/kg bw for females, respectively.

Executive summary:

In an acute oral toxicity study young adult Wistar rats (5 animals per sex and dose) were orally exposed to aluminium chloride in water at six increasing dose levels to confirm both LD0 and LD100 values. Animals were observed for 14 days. The treatment related clinical signs were hematuria and bloody stool. Pathology abnormalities observed were congestion of stomach and brain. The oral LD50 value in was considered to be 3470 mg/kg bw and 3450 mg/kg bw, for females and males, respectively.

       

- This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 3 450 mg/kg bw

Quality of whole database:

Read-across study rated as Klimisch 2 performed similar to OECD TG 401.

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:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Limit test:

no

Duration of exposure:

h

Sex:

male

Dose descriptor:

LC0

Effect level:

> 1 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no mortality occurred after a post treatment observation period of up to six months

Mortality:

No mortality was observed.

Clinical signs:

other: No adverse signs of toxicity were observed

Body weight:

No effects on body weight gain

Gross pathology:

see below

Other findings:

MICROSCOPY:
24 hours post exposure: little cellular response, but accumulation of black particulate material on the luminal surface of terminal airways
14 days post exposure: a prominent histiocytic cellular response was evident. Many of the alveolar macrophages contained phagocytized particulate material. However, there was a significant amount of black particulate material lying free within alveolar luminar. In the higher dose groups (200 mg/m3 and 1000 mg/m3), microgranulomas containing particulate material expanded the walls of terminal airways and alveolar septae. Intra-alveolar hypercellularity attributable to the histiocytic cellular response had a distinct peribronchiolar orientation, thus warranting a morphololgic diagnosis of bronchiocentric granulomatous pneumonia. Examination of hilar lymph nodes at 14 days PE revealed the presence of black particulate material.
The microscopic changes evident at 14 days PE were still present at 3 and 6 months PE. Black particulate material (aluminum flake) was present in histiocytic alveolar macrophages and within microgranulomas expanding the walls of terminal airways and alveolar septae.

PHYSIOLOGICAL EVALUATIONS:
No adverse physiological response was notified

BRONCHOPULMONARY LAVAGE FLUID ANALYSES:
Significant increases in ALKP, protein, LDH and G-6-PD examined at 14 days PE. More importantly, these changes persisted at 3 months post exposure and even at 6 months post exposure in the 50 mg/m3 group held and examined at that late date. The only change in the pulmonary lavage fluid of the 10 mg/m3 exposed rats was a slight increase in ALKP.
Cytological analyses showed an increase in total cells and an influx of polymorphonuclear neutrophils (PMN) after 24 hours post exposure. These changes did not diminish after 14 days, 3 months or 6 months. There were no changes in the lavage fluid of rats exposed to 10 mg/m3 of aluminum powder. The slight increase in PMNs at the 10 mg/m3 exposure level was attributed to increases from one rat.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation study with Aluminum flakes no mortality occured in male F-344 Fischer rats. Based on the results the LC0 of aluminum powder is greater than 1 mg/L.

Executive summary:

In an acute inhalation toxicity study, 10-12 weeks old male F-344 Fischer rats, 6 males/group, were exposed by whole body inhalation to aluminum powder (99% purity) for 4 hours at concentrations of 10, 50, 100, 200 and 1000 mg/m³. Animals were observed 24 hours, 14 days, 3 and 6 months post exposure. No mortality occurred.

Additionally, analyses of the lung lavage fluid revealed a persistent increase in alkaline phosphatase, lactate dehydrogenase, glucose-6 phosphate dehydrogenase and protein after 14 days and beyond. In addition a chronic irritant response was also apparent in the cytological analysis as polymorphonuclear neutrophils increased, followed by an increase in the macrophages, which is a typical sign for an acute inflammatory response. Since no mortality occured during the entire observation period, the LC50 can be considered to be greater than 1 mg/L.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC0

Value:

> 1 000 mg/m³ air

Physical form:

inhalation: dust

Quality of whole database:

Read-across study rated as Klimisch 2 performed similar to OECD TG 403.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

For human health endpoints, the relative bioavailability of different metal-ions from "Neutralisation and reduction products of bauxite residue from refinement process" would determine its potential to cause toxicological effects and also govern the severity of such effects. According to the results of the bioelution testing, aluminium has the highest relative release into artificial physiological media representing relevant exposure routes and therefore was considered as main constituent for the human health hazard/risk assessment of the substance.

No acute toxicity data are available for the target substance. In the absence of substance-specific data for the substance, a conservative approach to hazard evaluation is to assume that aluminium released from the substance shows the same systemic hazards as other aluminium compounds with similar or higher bioavailability. Read-across to aluminium compounds with a high release of aluminium ions (soluble Al salts) is considered to represent a worst-case approach that overestimates toxicological properties of the target compound. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Therefore, suitable data from the read across partner aluminium chloride was used for assessment of oral acute toxicity.In an acute oral toxicity study, young adult Wistar rats were orally exposed to the highly soluble aluminium chloride. The oral LD50 was considered to be 3470 mg/kg bw and 3450 mg/kg bw, in females and males, respectively.

Based on the results of the bioelution tests compounds with low solubility (i.e. aluminium) were considered suitable read-across partners for acute inhalation effects.

In an acute inhalation study, rats were exposed to a concentration up to 1000 mg/m³ of aluminium flakes for four hours. No mortality was observed during a 6 months post-exposure period. Thus, the LC50 can be considered to be greater than 1000 mg/m³.

 

Justification for classification or non-classification

Based on the data available from analogue substances within the read-across approach, the target substance does not warrant classification for acute toxicity. The LD50 values for aluminium chloride administered via the oral route are 3470 mg/kg bw and 3450 mg/kg bw, in females and males, respectively. The LC50 value received from an acute inhalation study was greater than 1000 mg/m³ for aluminium powder.