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EC number: 212-766-5 | CAS number: 867-64-1
Repeated dose toxicity - oral
No studies on oral repeated dose toxicity are available for gadolinium oxalate. The endpoint is therefore covered using a study performed with the related substance gadolinium oxide. The key read across study (Papineau, 2017) was performed according to OECD guideline 422 and conform GLP requirements. In this study, gadolinium oxide was administered by oral gavage to male and female Sprague-Dawley rats, starting 2 weeks before mating, during mating and (for females) throughout gestation and until day 5 post-partum, at the dose levels of 110, 330 or 1200 (until day 17 of the study)/1008 (from day 18 of the study until end of exposure) mg/kg bw/day. In this study, the NOAEL for parental systemic toxicity was considered to be higher than or equal to 1008 mg/kg bw/day based on the absence of adverse findings related to the test item at the highest dose level. This is equivalent to a NOAEL higher than or equal to 1609 mg/kg bw/day when recalculated to gadolinium oxalate taking into account the gadolinium content of both substances. Based on these results, neither gadolinium oxide nor gadolinium oxalate need to be classified as STOT RE. The justification for read across is attached to IUCLID Section 13.
Repeated dose toxicity - inhalation/dermal
No key studies were identified for repeated dose toxicity after inhalation or dermal exposure to gadolinium oxalate.
A key read across 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 or dermal route of exposure.
The table below presents the main differences in blood biochemistry parameters when compared with control values:
In a reliable, GLP-compliant study performed according to OECD guideline 422 (Papineau, 2017), the read across substance gadolinium oxide was administered once daily to 3 groups of 10 male and 10 female Sprague-Dawley rats by oral administration (gavage) at dose levels of 110, 330 or 1200 (until day 17 of the study)/1008 (from day 18 of the study until end of exposure) mg/kg bw/day. The dosing period started 2 weeks before mating, continued during mating, and for females, throughout gestation until day 5 post-partum. The test item was administered in the vehicle (0.5% methyl cellulose aqueous solution) under a constant dosage volume of 5 mL/kg bw/day, with the exception of the group receiving the highest dose level, for which the dosage-volume was 4.2 mL/kg bw/day from day 18 of the study onwards in order to achieve a dose level of 1008 mg/kg/day. One other group of 10 males and 10 females received the vehicle alone and acted as a control group.
Actual concentrations of the test item in the dose formulations analysed during the study (weeks 1 and 7) remained within an acceptable range of variations (-7.0% to +3.9%) when compared to the nominal values (nominal concentration +/-15%). There were no unscheduled test item-related deaths. Clinical signs were of isolated occurrence (e.g., piloerection) or commonly observed when test item is administered by gavage (e.g., ptyalism) and were therefore not considered to be adverse. There were no effects on body weight, body weight gain, food consumption, functional observation battery tests or motor activity data in any group or sex. Haematological differences, clinical biochemistry findings, and histopathological findings were not related to treatment with the test item. No test item-related changes were observed during gross pathological examination. Based on the experimental conditions of this study, the NOAEL for parental systemic toxicity was considered to be higher than or equal to 1008 mg/kg bw/day based on the absence of adverse findings related to the test item at this high dose level. This is equivalent to a NOAEL of 1609 mg/kg bw/day when recalculated to gadolinium oxalate taking into account the gadolinium content of both substances. This study is considered as the key study for endpoint coverage. The read across justification is attached to IUCLID Section 13.
Repeated dose toxicity - inhalation/dermal
No information has been identified on the repeated dose toxicity of gadolinium oxalate after inhalation or dermal exposure. A key read across 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).
Anyhow, low exposure to gadolinium oxalate is expected based on the inherent properties of this compound. No vapour pressure value has been determined as gadolinium oxalate does not melt below 300°C. Therefore, inhalation of gadolinium oxalate as a vapour is not likely to occur.
Further, gadolinium oxalate is typically manufactured as wet powder. Thus, the formation of respirable suspended particulate matter is unlikely. Occasionally manufactured dry powders typically have a D50 > 50 μm, which implies that no or only a very limited fraction of the powders may be respirable and capable of reaching the alveolar region of the lungs. Consequently, human exposure by inhalation is considered not significant for this compound.
Finally, the dermal route of exposure is not considered relevant either due the poor water solubility of gadolinium oxalate.
Consequently, it is not necessary to perform a repeated dose toxicity study via the inhalation or dermal route of exposure.
Based on the NOAEL value of higher than or equal to 1609 mg/kg bw/day, recalculated from the NOAEL of higher than or equal to 1008 mg/kg bw/day obtained in an OECD 422 study performed with the read across substance gadolinium oxide, gadolinium oxalate is not to be classified for Specific Target Organ Toxicity after Repeated Exposure (STOT RE) according to the CLP Regulation.
Repeated dose toxicity - inhalation
No key repeated dose toxicity study via inhalation is available.
Repeated dose toxicity - dermal
No key repeated dose toxicity study via dermal application is available.
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