Aluminium trilactate

Endpoint summary

Description of key information

The lowest NOAEL is reported by Pettersen et al. Following dietary administration of basic Sodium aluminium phosphate to beagle dogs for 26 weeks the NOAEL (males) was 27 mg Al/kg bw/d. 
Recalculation to the corresponding dose of Aluminium trilactate resulted in 294.41 mg/kg bw/d.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)

Deviations:

yes

Remarks:

duration of treatment extended to 180 days

GLP compliance:

not specified

Limit test:

yes

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Marshall Research Animals (North Rose, NY)
- Age at study initiation: 20 to 22 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: individually in stainless steel cages, exercised weekly
- Diet (e.g. ad libitum): Purina Certified Canine Diet #5007 + basic sodium aluminium phosphate + small amount of Mazola corn oil (0.5% w/w); 400 g of blended diet containing basic sodium aluminium phosphate was provided to each dog in a 3-hour feeding period
- Water (e.g. ad libitum): no data
- Acclimation period: ca. 5 weeks

ENVIRONMENTAL CONDITIONS
no data

Route of administration:

oral: feed

Vehicle:

corn oil

Details on oral exposure:

Four-hundred grams of blended diet containing basic sodium aluminium phosphate was provided to each dog in a 3-hour feeding period.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The test diets were blended biweekly and stored at room temperature. The concentration and homogeneity of basic sodium aluminium phosphate in each of the blended diets were determined monthly by analysis of aluminum content using atomic absorption spectrophotometry.

Duration of treatment / exposure:

26 weeks

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
106, 323, 1251 mg basic Sodium aluminium phosphate/kg bw/d (females)
Basis:
actual ingested

Remarks:

Doses / Concentrations:
112, 390, 1143 mg basic Sodium aluminium phosphate/kg bw/d (males)
Basis:
actual ingested

Remarks:

Doses / Concentrations:
3, 10, 22, 80 mg Al/kg bw/d (females)
Basis:
actual ingested

Remarks:

Doses / Concentrations:
4, 10, 27, 75 mg Al/kg bw/d (males)
Basis:
actual ingested

Remarks:

Doses / Concentrations:
0, 3000, 10000 or 30000 p.p.m. basic Sodium aluminium phosphate
Basis:
nominal in diet

No. of animals per sex per dose:

4

Control animals:

yes, plain diet

Positive control:

no

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes :

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Basic sodium aluminium phosphate consumption was calculated from each animal's weekly food consumption and body weight. Aluminium consumption was calculated from each animal's weekly food consumption, body weight as well as the mean aluminum concentrations calculated for basal and blended diet.

FOOD EFFICIENCY: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Blood samples were collected for clinical laboratory analyses from all animals prior to study initiation, near midpoint and at termination. The
dogs were fasted for at least 16 hours prior to sample collection. Blood samples were collected from the jugular vein in the morning. Hematocrit, haemoglobin concentration, erythrocyte count, leukocyte count (total and differential), and platelet count were determined.

CLINICAL CHEMISTRY: Yes
- Blood samples were collected for clinical laboratory analyses from all animals prior to study initiation, near midpoint and at termination. The
dogs were fasted for at least 16 hours prior to sample collection. Blood samples were collected from the jugular vein in the morning. Serum chemistry measurements included blood urea nitrogen, creatinine, sodium, potassium, chloride, phosphorus, alanine aminotransferase, aspartate
aminotransferase, alkaline phosphatase, gamma glutamyl transferase, sorbitol dehydrogenase, total bilirubin, total protein, albumin, globulin, glucose, calcium, cholesterol, and triglyceride.

URINANALYSIS: Yes
- Urine samples were collected for clinical laboratory analyses from all animals prior to study initiation and at termination. Urine samples were collected overnight using metabolism cages.

NEUROBEHAVIOURAL EXAMINATION: No

OTHER:
- FECALANALYSIS: Yes
-- Faecal samples were collected for clinical laboratory analyses from all animals prior to study initiation and at termination. Faecal samples were collected overnight using metabolism cages.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
- Organs weighed at necropsy included heart, liver, kidneys, ovaries, testes, thyroid, adrenals, and brain. Specimens from all major organs (not mentioned in detail) were fixed by immersion in 10% neutral buffered formalin or 2.5% buffered glutaraldehyde and processed for light microscopic examination.

Other examinations:

- Bone aluminium analysis: The aluminum concentration of trabecular bone and brain specimens were determined. Trabecular bone specimens were obtained from the fight and left femurs and brain specimens from the frontal cortex. Tissue samples were prepared for aluminum analysis in a Class 10-100 clean room. The samples were digested with NBS (National Bureau of Standards Purified Reagent) nitric acid. Aluminum in the resulting solution was determined with a Perkin-Elmer 5000 (Norwalk, CT) atomic absorption spectrophotometer equipped with a graphite furnace and Zeeman background correction system. Limits of detection and quantitation of tissue aluminum concentrations were calculated as described by Long and Winefordner (1983) and the American Chemical Society's Committee on Environmental Improvement (1980). The limit of detection for a sample was the lowest concentration measured that was statistically different from the blank sample concentration. In a similar manner, the limit of quantitation was also calculated from the blank analysis data that assured that the measured value was a precise number. For ,these studies, concentration values for aluminum below the detection limit were reported as not detected, values between the limit of detection and the limit of quantitation could not be precisely measured and were therefore reported as a range, and values that exceeded the limit of quantitation were assigned numerical values. Tissue aluminum concentrations were analyzed statistically by a one-way analysis of variance followed by Neuman-Keuls tests. Statistical significance was accepted at p<0.05.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Findings were limited to high dose males.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Findings were limited to high dose males. For actual ingested doses see section "Doses/concentrations"

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Findings were limited to high dose males.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Findings were limited to high dose males.

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: There were no mortalities during the study. No data on clinical signs.

BODY WEIGHT AND WEIGHT GAIN and FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): There was a sharp, transient decrease of food consumption and a concomitant decrease of body weight in high-dose males. No effect on food consumption and body weight was observed in females. For actual ingested dose see section "Doses/concentrations"

FOOD EFFICIENCY: not examined

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): no data

OPHTHALMOSCOPIC EXAMINATION: no data

HAEMATOLOGY, CLINICAL CHEMISTRY and URINALYSIS: No treatment-related effects on serum chemistry, haematology or urinalysis were observed.

NEUROBEHAVIOUR: not examined

ORGAN WEIGHTS and HISTOPATHOLOGY: NON-NEOPLASTIC: Findings were limited to a decrease in testes weight in high dose males and microscopic changes which included mild to moderate hepatocyte vacuolation accompanied by hepatocyte hypertrophy and mild bile stasis involving bile
cannuliculi (three of four animals). Two high-dose males had moderate seminiferous tubule germinal epithelial cell degeneration and atrophy. Changes in both organs were probably a consequence of the large body weight effect observed in these animals. Other changes included very mild to mild tubular-glomerularnephritis in high-dose males.

GROSS PATHOLOGY: no effects

HISTOPATHOLOGY: NEOPLASTIC (if applicable): not examined

HISTORICAL CONTROL DATA (if applicable): not relevant

OTHER FINDINGS
- Individual animal tissue aluminum concentrations were determined in triplicate. To provide for a conservative method and aid in statistical analysis, individual mean values were calculated by using the highest possible aluminum concentration for each determination (i.e., detection limit, limit of quantitation or actual value). These individual mean values were utilized for calculation of group mean values and for statistical analysis. Using this approach, group mean trabecular bone aluminum concentrations in males or females fed basic sodium aluminium phosphate were not significantly different from control.Similarly, brain aluminum concentrations were comparable among control and KASAL-treated males. In contrast, brain aluminum concentrations were significantly increased (p<0.05, values were 1.6 times greater than control), in high-dose (30,000 p.p.m.) females relative to control while no effect was apparent at lower KASAL dose levels.

Dose descriptor:

NOAEL

Effect level:

27 mg/kg bw/day (actual dose received)

Based on:

element

Remarks:

Aluminium

Sex:

male

Basis for effect level:

other: overal effects

Dose descriptor:

LOAEL

Effect level:

75 mg/kg bw/day (actual dose received)

Based on:

element

Remarks:

Aluminium

Sex:

male

Basis for effect level:

other: reduced body weights and food consumption with accompanying histopathological findings in liver, testes, and kidneys

Dose descriptor:

NOAEL

Effect level:

80 mg/kg bw/day (actual dose received)

Based on:

element

Remarks:

Aluminium

Sex:

female

Basis for effect level:

other: overall effects / highest dose tested

Dose descriptor:

NOAEL

Effect level:

390 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

basic Sodium aluminium phosphate

Sex:

male

Basis for effect level:

other: overall effects / dose corresponds to 10.000 ppm basic Sodium aluminium phosphate in diet

Dose descriptor:

LOAEL

Effect level:

1 143 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

basic Sodium aluminium phosphate

Sex:

male

Basis for effect level:

other: reduced body weights and food consumption with accompanying histopathological findings in liver, testes, and kidneys / dose corresponds to 30.000 ppm basic Sodium aluminium phosphate in diet

Dose descriptor:

NOAEL

Effect level:

1 251 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

basic Sodium aluminium phosphate

Sex:

female

Basis for effect level:

other: overall effects / highest dose tested corresponding to 30.000 ppm basic Sodium aluminium phosphate in diet

Critical effects observed:

not specified

Conclusions:

In this study, dietary administration of basic Sodium aluminium phosphate, to beagle dogs for 26 weeks resulted in decreased food consumption, decreased body and testis weight and histopathological changes in liver, testes and kidney of male dogs after 75 mg Al/kg bw/d. No effects were seen in females. The NOAEL was 390 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 27 mg Al/kg bw/d in male beagle dogs. The NOAEL in female beagle dogs was the highest dose tested of 1251 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 80 mg Al/kg bw/d.

Executive summary:

In a repeated dose toxicity study comparable to OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents), male and female Beagle dogs were exposed basic Sodium aluminium phosphate at dose levels of 0, 3000, 10000 and 30000 ppm in their diets. Based on Aluminium measurements, food consumption and body weights, the male animals received 0, 112, 390 and 1143 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 4, 10, 27 and 75 mg Al/kg bw/d and the female animals 0, 106, 323 and 1251 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 3, 10, 22 and 80 mg Al/kg bw/d. In deviation to the guideline mentioned, study duration was 26 weeks and not 13 weeks. In-life observation findings were limited to a sharp, transient decrease of food consumption and a concomitant decrease of body weight in high-dose males. No effect on food consumption and body weight was observed in females. No treatment-related effects on serum chemistry, haematology or urinalysis were observed. No animal died during the study. Postmortem observations findings were limited to a decrease in testes weight in high-dose males and microscopic changes which included mild to moderate hepatocyte vacuolation accompanied by hepatocyte hypertrophy and mild bile stasis involving bile cannuliculi (three of four animals). Two high-dose males had moderate seminiferous tubule germinal epithelial cell degeneration and atrophy. According to discussion of the study authors, changes in both organs were probably a consequence of the large body weight effect observed in these animals. Other changes included very mild to mild tubular-glomerularnephritis in high-dose males. The NOAEL was 390 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 27 mg Al/kg bw/d in male beagle dogs. The NOAEL in female beagle dogs was the highest dose tested of 1251 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 80 mg Al/kg bw/d.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

294.41 mg/kg bw/day

Study duration:

chronic

Species:

dog

Quality of whole database:

All reported studies are of high quality (Klimisch score=2).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No reliable OECD key study is available on the repeated dose toxicity of Aluminium trilactate. Data on other Aluminium compounds have been used, as it is assumed that after intake Aluminium trilactate is changed to ionic Aluminium and Lactate and that only ionic Aluminium is determining biological activities. A full read-across of data based on Aluminium content and a molecular weight correction is considered for Aluminium trilactate.

NOAELs derived for Aluminium are as follows:

In a combined repeated dose / reproductive screening study according to OECD guideline 422 male and female Wistar rats were exposed to Aluminium chloride, basic by oral gavage at dose levels of 40, 200 or 1000 mg/kg bw/d (equivalent to 3.6, 18 or 90 mg Al/kg bw/d). 10 animals/sex/group were used. Males were exposed for 28 days, females between 37 and 53 days (because of the developmental toxicity purpose of study). Detailed clinical signs, body weight, food consumption, water consumption (subjective appraisal), haematology, clinical chemistry, neurobehaviour, gross pathology and histopathology were studied.

Slightly lower mean bodyweight was observed for females at the 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d) group at day 8, with slight weight loss for three of these females. Bodyweight recovered during the following mating and post-coital period. In the other groups no deviations were observed as compared to controls.

Mean food consumption of females at 1000 mg/kg bw/d (equivalent to 90 mg/kg bw/d) was slightly lower than controls. Otherwise no deviations were observed as compared to controls.

Minor, but statistically significant lowering of MCHC was observed in males and females of the 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d) group. Minor, but statistically significant higher platelet count was observed in males at a dose of 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d).

Males at 1000 mg/kg bw/d had statistically significant lower ALP activity, lower albumin levels, higher Potassium levels, higher inorganic phosphate levels. No deviations were observed in males and females at doses of 40 and 200 mg/kg bw/d (equivalent to 3.6 and 18 mg Al/kg bw/d).

Red foci on glandular mucosa of the stomach were observed in 5 of 10 males at a dose of 1000 mg/kg/d (equivalent to 90 mg Al/kg bw/d), with thickening of glandular mucosa or limiting ridge in two of these five. No other relevant abnormalities were seen.

Mild to moderate subacute inflammation of the glandular mucosa and minimal to moderate superficial eosinophilic spheroids was observed in all examined animals of both sexes at 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d).

The NOAEL for local (stomach) toxicity in males is 200 mg/kg bw/d (equivalent to 18 mg Al/kg bw/d). The LOAEL for local (stomach) toxicity in males is 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d). The NOAEL for systemic toxicity in males is 1000 mg/kg bw/d (equivalent to 90 mg Al/kg/d Al). The NOAEL for local and systemic toxicity in females is 1000 mg/kg bw/d (equivalent to 90 mg Al/kg bw/d).

In a subchronic toxicity study according to OECD guidelines 426 and 452 Aluminium Citrate was administered to 20 female Sprague-Dawley rats in drinking water at dose levels of 30, 100, 300 mg Al/kg bw/d. Two control groups received either a sodium citrate solution (citrate control with 27.2 g/L) or plain water (control group). The Al citrate and Na citrate were administered to dams ad libitum via drinking water from gestation day 6 until weaning of offspring (PND 22).

Endpoints and observations in the dams included water consumption, body weight, a Functional Observational Battery (FOB), morbidity and mortality.

As the F1 generation was dosed during the whole post-weaning period, it is difficult to differentiate between developmental or direct toxicity after weaning. Thus, for the assessment of repeated dose toxicity only the data obtained from the dams are used.

No maternal toxic effects were observed up to 300 mg Al/kg bw/d. In this study, the maternal NOAEL was 300 mg Al/kg bw/d.

In a subchronic toxicity study similar to OECD guideline 408 Aluminium nitrate nonahydrate was administered to 10 female Sprague-Dawley rats/dose in drinking water for 100 days at dose levels of 0,360, 720 and 3600 mg/kg bw/d, corresponding to 0, 26, 52 and 260 mg Al/kg bw/d. At 260 mg Al/kg bw/d, a statistically significant decrease in body weight gain and food and water consumption was observed. All other toxicological parameters measured were not or not significantly changed in relation to the exposure. Aluminium concentrations in the tissues examined were higher in the treated rats than in the control animals, but no significant relationship between dose and accumulation was observed. At 26 and 52 mg Al/kg bw/d no significant toxic effects were reported, therefore the NOAEL is 52 mg Al/kg bw/d. The LOAEL is 260 mg Al/kg bw/d.

In a repeated dose toxicity study comparable to OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity in Non-Rodents), male and female Beagle dogs were exposed basic Sodium aluminium phosphate at dose levels of 0, 3000, 10000 and 30000 ppm in their diets. Based on Aluminium measurements, food consumption and body weights, the male animals received 0, 112, 390 and 1143 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 4, 10, 27 and 75 mg Al/kg bw/d and the female animals 0, 106, 323 and 1251 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 3, 10, 22 and 80 mg Al/kg bw/d. In deviation to the guideline mentioned, study duration was 26 weeks and not 13 weeks. In-life observation findings were limited to a sharp, transient decrease of food consumption and a concomitant decrease of body weight in high-dose males. No effect on food consumption and body weight was observed in females. No treatment-related effects on serum chemistry, haematology or urinalysis were observed. No animal died during the study. Postmortem observations findings were limited to a decrease in testes weight in high-dose males and microscopic changes which included mild to moderate hepatocyte vacuolation accompanied by hepatocyte hypertrophy and mild bile stasis involving bile cannuliculi (three of four animals). Two high-dose males had moderate seminiferous tubule germinal epithelial cell degeneration and atrophy. According to discussion of the study authors, changes in both organs were probably a consequence of the large body weight effect observed in these animals. Other changes included very mild to mild tubular-glomerularnephritis in high-dose males. The NOAEL was 390 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 27 mg Al/kg bw/d in male beagle dogs. The NOAEL in female beagle dogs was the highest dose tested of 1251 mg basic Sodium aluminium phosphate/kg bw/d, corresponding to 80 mg Al/kg bw/d.

EFSA (2008),WHO IPCS EHC (World Health Organistion International Programme on Chemical Safety Environmental Health Criteria) (1997) andFAO/WHO JECFA (Joint Food and Agriculture Organisation of the United Nations/World Health Organisation Expert Committee on Food Additives) (2007), have reviewed several more publications on subchronic and chronic toxicity of various Aluminium compounds in different species. These were also taken into account for the hazard assessment of Aluminium trilactate. A short summary of the most important results is given in the table below:

 

substance	species, duration	NOAEL	original reference	cited in
Al(NO3)3	Female Sprague-Dawley rats (n=10); 28 d	NOAEL = 52 mg Al/kg bw/d	Gómez et al., 1986	EFSA, 2008;WHO IPCS EHC, 1997
Al(OH)3	Male Sprague-Dawley rats (n=25); 28 d	NOAEL = 302 mg Al/kg bw/d	Hicks et al., 1987	EFSA, 2008;WHO IPCS EHC, 1997
KASAL I 6% SALP basic	Male Sprague- Dawley rats (n=25); 28 d	NOAEL = 141 mg Al/kg bw/d	Hicks et al., 1987	EFSA, 2008;WHO IPCS EHC, 1997
KASAL II 13% SALP basic	Male Sprague- Dawley rats (n=25); 28 d	NOAEL = 288 mg Al/kg bw/d	Hicks et al., 1987	EFSA, 2008;WHO IPCS EHC, 1997
sodium aluminium phosphate, acidic	male and female Beagle dogs (4/sex); 26 weeks	males: NOAEL = 88 mg Al/kg bw/d females: NOAEL = 93 mg Al/kg bw/d	Katz et al., 1984	EFSA, 2008;WHO IPCS EHC, 1997; WHO, 2007

 

The effect levels obtained from the selected key and supporting studies were recalculated to a corresponding dose of Aluminium trilactate:

 

Source	Endpoint	Al [mg/kg bw/d]	Al trilactate [mg/kg bw/d]
Beekhuijzen, 2007, OECD TG 422 study	28 d NOAEL	90	981.36
ToxTest, 2010, OECD TG 426/452 study	1 yr NOAEL	300	3271.2
Domingo et al, 1987	100 d NOAEL	52	567.01
Pettersen et al., 1990	26 wk NOAEL, males	27	294.41
	26 wk NOAEL females	80	872.32
Source	Endpoint	Lactate [mg/kg bw/d]	Al trilactate [mg/kg bw/d]
Andersen, 1998 /Matsushima	13 wk NOAEL	408.17	449.33

 

The lowest NOAEL from the study with the longest exposure duration is reported by Pettersen et al.: Following dietary administration of basic sodium aluminium phosphate to beagle dogs for 26 weeks the NOAEL (males) was 27 mg Al/kg bw/d.

Recalculation to the corresponding dose of Aluminium trilactate resulted in 294.41 mg/kg bw/d.

 

Inhalation

A study on repeated dose toxicity via inhalatory route is unjustified in accordance to REACH regulation Annex IX, column 2 due to exposure considerations as well as in accordance to REACH regulation Annex XI due to scientific considerations. The test substance has a high melting point (> 300°C) and thus a very low vapour pressure, so the potential for the generation of inhalable forms is low. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore, there are no indications on systemic toxicity relevant to humans neither from acute nor from repeated dose toxicity studies performed on reliable, relevant, adequate read across substances by oral exposure. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative systemic toxicity risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

 

Dermal route

A study on repeated dose toxicity by dermal exposure is unjustified in accordance to REACH regulation Annex XI due to scientific considerations. It can reasonably be deduced that Aluminium trilactate does not exert systemically toxic effects after dermal application. Considering that there are no indications on systemic toxicity relevant to humans neither from acute nor from repeated dose toxicity studies performed on reliable, relevant, adequate read across substances by oral exposure and the low systemic availability via the intact skin barrier (see section “Toxicokinetics, metabolism and distribution”), systemic toxicity after dermal exposure is unlikely. Furthermore the substance does not have to be classified as skin irritating. Therefore, testing is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

 

References

Andersen (1998) Final Report on the safety assessment of glycolic acid, […], and lactic acid, ammonium, calcium, potassium, sodium, and TEA-lactates […], International Journal of toxicology, 17, Suppl. 1

EFSA (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

FAO/WHO JECFA (Joint Food and Agriculture Organisation of the United Nations/World Health Organisation Expert Committee on Food Additives)(2007) Safety evaluation of certain food additives and contaminants. WHO FOOD ADDITIVES SERIES: 58, World Health Organization, Geneva, 2007, available via internet: http://whqlibdoc.who.int/publications/2007/9789241660587_eng.pdf

WHO IPCS EHC (World Health Organistion International Programme on Chemical Safety Environmental Health Criteria)(1997) Aluminium (Environmental health criteria; 194), IPCS, World Health Organization, Geneva, available via internet: http://www.inchem.org/documents/ehc/ehc/ehc194.htm  

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study with the lowest NOAEL and longest duration was chosen as key study.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
no relevant route of exposure

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
no relevant route of exposure

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
low dermal absorption

Justification for classification or non-classification

In conclusion, the results of the available data on repeated dose toxicity indicate that Aluminium trilactate, does not need to be classified for repeated dose toxicity according to Directive 67/548/EEC as well as CLP, EU GHS (Regulation 1272/2008/EC) and therefore labelling is not necessary.