Lanthanum trinitrate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction:

Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in RccHan: WIST (SPF) rats. The read-across substance lanthanum acetate was administered to male rats for 46 days and to female rats for 14 days prior topairing, 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 treated with 1000 mg/kg bw/day were significantly reduced (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 toxicological relevance. 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 of the 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.

There were no treatment-related effects on mating performance and fertility, duration of gestation, number of corpora lutea, mean litter sizes and post natal loss. No differences on the completeness of stages or cell populations of the testes were recorded between control and high dose animals. No test item-related histological findings were recorded in the testis nor in the ovary. Therefore, the NOEL/NOAEL for reprotoxicity was considered to be >= 1000 mg/kg bw/day.

The pups were without clinical signs, their body weight development was similar in all groups, and there were no macroscopical findings of toxicological relevance. The sex ratios at first litter check were considered to be unaffected by the treatment with the test item. Therefore, the NOEL/NOAEL for developmental toxicity was considered to be >= 1000 mg/kg bw/day.

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.

Short description of key information:

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

The read across justification is added in Section 13 of IUCLID.

Justification for selection of Effect on fertility via oral route:

The study was performed with the read-across substance lanthanum acetate, another 'water-soluble' lanthanum compound. 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. The dose of >= 1000 mg/kg bw/day was considered to be the NOEL/NOAEL value.

Justification for selection of Effect on fertility via inhalation route:

only one route of exposure os needed for this endpoint

Justification for selection of Effect on fertility via dermal route:

only one route of exposure os needed for this endpoint

Effects on developmental toxicity

Description of key information

One study is available with the read-across substance lanthanuma cetate, another 'water-soluble' lanthanum compounds. Braun (2013) performed a combined repeated dose toxicity study (scored K1) with reproduction/developmental toxicity screening test in rats according to OECD guideline 422 (GLP). No adverse effects were observed. A NOEL/NOAEL of 1000 mg/kg bw/day (the highest dose tested; limit dose in this type of study) was derived for developmental toxicity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

An OECD 422 test has been performed with the read-across substance lanthanum acetate. The results of the reproduction/developmental toxicity screening test indicate that lanthanum acetate is a substance of low toxicological potential, as the NOEL/NOAEL for reproductive/developmental toxicity was considered to be >= 1000 mg/kg bw/day (the highest dose tested, expressed as anhydrous lanthanum acetate). Furthermore no effects were observed in litter and sex ratios and any of the parameters evaluated for pups (clinical signs). No treatment-related findings were recorded at necropsy.

In addition, and based on the assessment of all available data, low absorption of lanthanum trinitrate is expected (See toxicokinetic assessment in Section 7.1). Therefore, as no adverse effects or hazards need to be addressed, no further testing is required for this substance

No additional developmental toxicity test is thus proposed.

The read across justification is added in Section 13 of IUCLID.

Justification for selection of Effect on developmental toxicity: via oral route:

An OECD 422 study including a reproduction/developmental toxicity screening is available for lanthanum acetate, another 'water-soluble' lanthanum compound. The robust study summary is included in endpoint 7.8.1. The dose of 1000 mg/kg bw/day was considered to be the NOEL/NOAEL value.

Justification for classification or non-classification

Based on the available data of the read-across substance lanthanum acetate and according to the DSD and CLP criteria, lanthanum trinitrate should not be classified as toxic to reproduction.