Cadmium nitrate

Endpoint summary

Description of key information

Available NOAELs from repeated dose oral and inhalation studies range between 0.12 - 3 mg/kg bw/day (studies with cadmium chloride) and 0.013. 10-3- 0.022 x 10-3mg/L (studies with cadmium oxide), respectively.
Repeated dose toxicity of cadmium via the dermal route is not expected given the relatively low skin penetration of all forms of this metal. Also in view of the risk reduction measures which need to be taken as a result of the carcinogenicity of cadmium metal and some of the cadmium compounds, chronic dermal toxicity is not expected to be an issue for human health.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

0.12 mg/kg bw/day

Study duration:

chronic

Species:

monkey

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

0.013 mg/m³

Study duration:

subchronic

Species:

hamster, Syrian

Additional information

Results from studies in animals and observations in humans indicate that the sensitive targets of cadmium toxicity are kidney and bone following oral exposure and kidney and lungs following inhalation exposure (ATSDR, 2008).

Cadmium being a cumulative toxicant, the systemic manifestations associated with chronic exposure are related to the body burden of the element (liver and kidney content), assessed with biomarkers such as urinary concentration (Cd-U). In workers exposed to cadmium, a body burden corresponding to 200 ppm in kidney cortex, ie ca. 10 μg Cd/g creatinine is considered to represent a critical level based on the occurrence of low molecular weight proteinuria.SCOEL (2010) recommends an Occupational Exposure Level (OEL) equivalent to 4 µg Cd/m3 (respirable fraction) as protective against long-term local effects (respiratory effects, including lung cancer). This is based on human data that shows changes in residual volume of the lung for a cumulative exposure to CdO fumes of 500 µg Cd/m3 x years, corresponding to 40 years exposure to 12.5 µg Cd/m3 (LOAEL) (Cortona et al., 1992). Applying an uncertainty factor of 3 (LOAEL to NOAEL) leads to a value of 4 µg/m3.

Based on the most recent studies, it seems that renal effects can be detected in the general European population (mainly exposed by the oral route) for cadmium body burdens at or even below 2 μg Cd/g creatinine.There is, however, a scientific debate about the health significance of these early changes. This lower value in the general population compared to that identified in workers is thought to reflect, among other parameters, an interaction of cadmium exposure with pre-existing, concurrent or subsequent renal diseases (mainly renal complications of diabetes) that are less prevalent in healthy young individuals in occupational settings. As workers exposed to cadmium may, however, suffer from such diseases during or most often after their occupational career, and considering the long half-life of cadmium in humans and its accumulation with age, it is considered prudent to recommend a Biological Limit Value (BLV) that would provide a sufficient degree of protection in this respect (SCOEL, 2010).

Available NOAELs from repeated dose oral and inhalation studies range between 0.12 - 3 mg/kg bw/day and 0.013. 10^-3- 0.022 x 10^-3mg/L, respectively. This data supports a classification as T; R48/23/25 (Toxic: danger of serious damage to health by prolonged exposure through inhalation and if swallowed), which has been attributed to cadmium chloride, sulphate, oxide and metal in Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be STOT category 1; H372). By analogy, the other highly and slightly soluble forms of cadmium (i.e. cadmium nitrate, hydroxide and carbonate) warrant comparable classifications.

Apart from cadmium sulphide, no other insoluble cadmium compounds (e.g. cadmium sulfoselenide, cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified for repeated dose toxicity. Cadmium sulphide is an exception. As there is no data to support its T; R48/23/25 classification, a revision of this classification may be appropriate based on solubility properties.

Repeated dose toxicity of cadmium via the dermal route is not expected given the relatively low skin penetration of all forms of this metal. Also in view of the risk reduction measures which need to be taken as a result of the carcinogenicity of cadmium metal and some of the cadmium compounds, chronic dermal toxicity is not expected to be an issue for human health. No corresponding classification is therefore required.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys; other: bone

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung; urogenital: kidneys

Justification for classification or non-classification

Available NOAELs from repeated dose oral and inhalation studies range between 0.12 - 3 mg/kg bw/day and 0.013. 10^-3- 0.022 x 10^-3mg/L, respectively. This data supports a classification asT; R48/23/25 (Toxic: danger of serious damage to health by prolonged exposure through inhalation and if swallowed), which has been attributed to cadmium chloride, sulphate, oxide and metal in Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be STOT category 1; H372). By analogy, the other highly and slightly soluble forms of cadmium (i.e. cadmium nitrate, hydroxide and carbonate) warrant comparable classifications.

Apart from cadmium sulphide, no other insoluble cadmium compounds (e.g. cadmium sulfoselenide, cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified for repeated dose toxicity. Cadmium sulphide is an exception. As there is no data to support its T; R48/23/25 classification, a revision of this classification may be appropriate based on solubility properties.

Repeated dose toxicity of cadmium via the dermal route is not expected given the relatively low skin penetration of all forms of this metal. Also in view of the risk reduction measures which need to be taken as a result of the carcinogenicity of cadmium metal and some of the cadmium compounds, chronic dermal toxicity is not expected to be an issue for human health. No corresponding classification is therefore required.