Lanthanum trinitrate

Endpoint summary

Description of key information

Repeated dose toxicity: oral

Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in rats with the read-across substance lanthanum acetate according to OECD Guideline 422 (GLP). A NOAEL for systemic toxicity of >= 1000 mg/kg bw/day was derived.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

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

Repeated dose toxicity: oral

Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in RccHan: WIST (SPF) rats with the read-across substance lanthanum acetate. Lanthanum acetate was administered to male rats for 46 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum (approximately 49 days).

Animals were exposed at 110, 330 and 1000 mg/kg bw/day dose levels (expressed as anhydrous active ingredient). Control animals were dosed with the vehicle (bi-distilled water) alone.

There were no effects upon mortality of parental animals, no clinical findings (daily or weekly), no differences in the functional observational battery (including grip strength and locomotor activity), no differences in mean absolute or relative organ weights, and no overt macroscopical findings of toxicological relevance.

At 1000 mg/kg bw/day, test-item related effects included reduced mean daily food consumption in males during the initial week of treatment, and in females during the first two weeks of treatment and during the second week of gestation, reduced body weights in males throughout the treatment period and in females intermittently during pre-pairing and gestation.The mean total protein, albumin and globulin levels of the males and females treated with 1000 mg/kg bw/day were significantlyreduced (p<0.01) when compared with the control values. These latter changes were considered to be related to the treatment with the test item. At 330 mg/kg bw/day, reduced total protein, albumin and globulin levels of females were considered to be the only findings of potential toxicological relevance. No changes were reported in males. These changes were considered conclusive but not sufficient for the derivation of a NOAEL value.

Test item related morphological changes were noted in animals treated with 330 and 1000 mg/kg bw/day, and included increased incidence and severity of inflammatory cell infiltration in submucosa to base of lamina propria of the stomach,and considered to be a reactive inflammatory lesion (gastritis) to a repeatedly gavaged test material.The severity was slightly higher in males than females. The inflammatory change was associated with eosinophilic globule leukocytes in mucosa, and sometimes with atrophy of fundic glands, eosinophilic chief cells and epithelial vacuolation ofthe squamous limiting ridge at minimal to slight severity. These changes were considered to be a local effect of the test item rather than one of systemic toxicological relevance.

The NOEL for toxicity of the parent animals was considered to be 110 mg/kg bw/day, based upon the changes in the stomachs of rats treated with 330 and 1000 mg/kg bw/day as well as differences in the mean daily food consumption and mean body weight at 1000 mg/kg bw/day. Although these changes were considered to be related to the treatment with the test item, the morphological changes in the stomachs were considered to be local effects rather than systemic toxicity and the differences in the food consumption/body weight were considered secondary to the changes in the stomach.

Therefore, the NOAEL for systemic toxicity of the parent animals was considered to be >= 1000 mg/kg bw/day (the highest dose tested; limit dose in this type of study).

The read-across justification is added in Section 13 of IUCLID. A maximal reliability score of 2 (reliable with restrictions) is assigned because the study has been used for read-across purposes in this dossier.

Repeated dose toxicity: inhalation

A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation. Furthermore, the substance is hygroscopic and forms aggregates. Therefore this study is not justified.

Repeated dose toxicity: dermal

A key study (read across) is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Read-across study from lanthanum acetate, another 'water-soluble' lanthanum salt. The read-across justification is added in Section 13 of IUCLID

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

A key study (read-across) is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure. Furthermore, the substance is hygroscopic and forms aggregates. Therefore this study is not justified.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:

A key study (read-across) is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure. Furthermore, the substance is hygroscopic and forms aggregates. Therefore this study is not justified.

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

A key study (read- across) is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

A key study (read across) is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Justification for classification or non-classification

Based on the available data of the read-across substance lanthanum acetate and supporting data on lanthanum trinitrate, and according to the criteria of the CLP Regulation, lanthanum trinitrate should not be classified for STOT repeated exposure via the oral route.