Aluminium trilactate

Endpoint summary

Description of key information

The oral LD50 value of Aluminium trilactate is greater than 2000 mg/kg bw (corresponding to > 183.4 mg Al3+/kg bw). No animal treated with this dose died. No clinical signs or effects on body weight were observed. Gross pathological examination revealed no test substance-dependent findings. 
In consideration of the missing acute toxicity by oral route and the systemic availability via the intact skin barrier (see section "Toxicokinetics, metabolism and distribution"), systemic toxicity after dermal exposure is unlikely. Therefore, testing of acute dermal toxicity is not scientifically necessary. 
Considering the exposure probability and the available information on the intrinsic toxic activity of the substance by oral route, an inhalative risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is also unjustified.

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:

1998-05-27 to 1998-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted March 22, 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

dated September 30, 1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar outbred rat; CrI:(WI) WU BR
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 122 - 143 g (females), 161 - 193 g (males)
- Fasting period before study: overnight. Approximately four houes after dosing, they had access to food again.
- Housing: maximum 5 animals per cage, stainless steel cages, fitted with wire screen floor and front
- Diet (e.g. ad libitum): standard laboratory rodent diet ad libitum(SDS Special Diets services, Whitham, England)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 6 - 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%):47.5-86% (upper limit higher than 70% due to wet cleaning, occurred for max. 1 hour)
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

IN-LIFE DATES: From: 27 May 1998 To: 19 June 1998

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight.
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: The exact amount of the test substance to be dosed was calculated for each animal individually.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not given

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 0, 3, 7, 14
- Frequency of observations: All visible reactions to treatment were recorded, including type, severity, onset and duration. Observations were made within 1 hour and within 4 houes after dosing, and subsequently at least once daily throughout an observation period of 14 days.
- Necropsy of survivors performed: yes

Preliminary study:

The study was started with treatment of three females with a 2000 mg/kg body weight dose level. Since all females survived the first days after treatment, it was decided to continue treatment with 3 males dosed with the 2000 mg/kg dose level.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

Aluminium-L-lactate

Remarks on result:

other: no animal died

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 183.4 mg/kg bw

Based on:

element

Remarks:

Al3+

Remarks on result:

other: no animal died

Mortality:

female 0/3 animals died
male 0/3 animals died

Clinical signs:

other: No abnormal clinical signs were observed.

Gross pathology:

Gross pathological examinations at 14 days p. a. (terminal necropsy) revealed no test substance dependent findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

Aluminium-L-lactate is practically nontoxic based on the oral LD50 (males/females) in rats of greater than 2000 mg/kg body weight (corresponding to 183.4 mg Al3+/kg bw).

Executive summary:

In an acute oral toxicity study (limit test, according to OECD guideline 423, adopted March 22, 1996), 3 male and 3 female Wistar rats were given a single oral dose of Aluminium-L-lactate in water of 2000 mg/kg bw (corresponding to 183.4 mg Al3+/kg bw, considering an amount of 9.17% Aluminium in Aluminium-L-lactate) and observed for 14 days.

No animal died in this study. No clinical signs or effects on body weight were observed. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test substance-dependent findings.

Oral LD50 Males and Females > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study (limit test, according to OECD guideline 423), 3 male and 3 female Wistar rats were given a single oral dose of Aluminium-L-lactate in water of 2000 mg/kg bw (corresponding to 183.4 mg Al3+/kg bw) and observed for 14 days. The oral LD50 formales and females was > 2000 mg/kg bw. No animal died in this study. No clinical signs or effects on body weight were observed. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test substance-dependent findings.

This finding is consistent with the range of LD50 values reported in literature. EFSA (2008), Krewski et al. (2007), US ATSDR (United States Agency for Toxic Substances and Disease Registry) (2008), Environment Canada (2010) have reviewed a number of acute oral toxicity studies with various Aluminium salts in rats and mice. When recalculated to Aluminium content, these values range from 162 mg Al3 +/kg bw to > 730 mg Al3+/ kg bw.The range of LD50 data obtained with intraperitoneal administration is narrower (25 to 133 mg Al3+/mg bw) than for oral administration. This indicates that the different Aluminium compounds have a similar potency based on the administered Aluminium dose. The range of potency after oral administration most likely depends on bioavailability (EFSA, 2008).

In consideration of the missing acute toxicity by oral route and the low systemic availability via the intact skin barrier (see section “Toxicokinetics, metabolism and distribution”), systemic toxicity after dermal exposure is unlikely. Therefore, testing of acute dermal toxicity is not scientifically necessary.

Considering the exposure probability and the available information on the low intrinsic toxic activity of the substance by oral route, an inhalative risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is also unjustified.

Based on the acute oral LD50>2000 mg/kg bw, a classification of Aluminium trilactate according to CLP, EU GHS (Regulation (EC) No 1272/2008) as acutely toxic is not justified.

 

References:

EFSA (European Food Safety Authority) (2008) Safety of aluminium from dietary intake, The EFSA Journal 754, 1-34, available via internet: http://www.efsa.europa.eu/de/efsajournal/pub/754.htm

Environment Canada (2010)Environment Canada Priority Substance List Assessment Report, Follow-up to the State of Science Report, 2000 Aluminium Salts (Final Content), available via internet: http://www.ec.gc.ca/lcpe-cepa/default.asp?lang=En&n=491F0099-1 and http://www.ec.gc.ca/lcpe-cepa/documents/substances/sa-as/final/al_salts-eng.pdf

US ATSDR (United States Agency for Toxic Substances and Disease Registry)(2008) Toxicological profile for Aluminium, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Public Health Service, Agency for Toxic Substances and Disease Registry, available via internet: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=191&tid=34

Krewski, et al. (2007). Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide, A Report Submitted to the US Environmental Protection Agency. J Toxicol Environ Health B Crit Rev. 10 Suppl 1:1-269. Available via internet: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782734/

Justification for selection of acute toxicity – oral endpoint
only one study available

Justification for classification or non-classification

There is no evidence on relevant intrinsic acute toxic activity of Aluminium trilactate constituting a hazard to human health. In rats, oral LD₅₀value is > 2000 mg/kg bw. No animal treated with this dose died. No clinical signs or effects on body weight were observed. Gross pathological examination revealed no test substance-dependent findings.

It can reasonably be deduced that Aluminium trilactate does not exert systemic toxic effects after dermal application, because Aluminium trilactate did not cause any effect after administration of a single oral dose of up to 2000 mg/kg bw in rats. Furthermore the substance does not have to be classified as skin irritating and it is unlikely that higher amounts than tested in the acute oral toxcity study will be systemically available via the intact skin barrier. Therefore, testing of acute dermal toxicity is scientifically not necessary.

The conduct of acute inhalative animal studies is also unjustified, as due to its very low vapour pressure, an exposure to Aluminium trilactate vapour is negligible. Inhalative exposure can be excluded based on conditions during use. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is unjustified.

Thus, Aluminium trilactate does not comply with the classification requirements regarding acute toxicity outlined in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC.