Chromium triacetate

Endpoint summary

Description of key information

NOAEL (90-d oral, rat) >= 2015 mg/kg bw/day

NOAEL (90-d oral, mouse) >= 4342 mg/kg bw/day

LOAEC, local  (90-d, inhalation, rat) = 21 mg/m³

NOAEC, systemic (90-d, inhalation, rat) = 210 mg/m³

NOAEL, dermal, systemic (extrapolation from 90-d oral rat) >= 2015 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

21 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, of Regulation (EC) No 1907/2006.

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

Subchronic oral administration of the source substance Cr(III) picolinate to mice and rats (10 animals/sex/dose) in a study performed similar to OECD 408 showed no substance-related effects regarding body weight, food consumption, haematology, clinical chemistry, gross pathology, organ weight determinations and histopathology (Rhodes et al., 2005). No death occured. The only clinical sign observed was reddening of the faeces of the high dose animals which was due the the reddish colour of the test susbtance. The NOAELs in rats and mice were ≥ 2015 and ≥ 4342 mg/kg bw/day, respectively, when corrected for the molecular weight of basic Cr(III) acetate monohydrate. The lack of systemic effects even at very high dietary levels are reflective of the poor oral bioavailability of Cr(III).

Subchronic inhalation exposure of rats (10 animals/sex/dose) to the source substance soluble basic chromium sulphate dust at 17, 54, or 168 mg/m³ in a study performed similar to OECD 413 produced effects on the respiratory tract without indications for systemic effects (Derelanko et al. 1999). Basic chromium sulphate produced severe and widespread effects in the nasal cavity, larynx, lungs, and mediastinal lymph node. Effects were characterized by accumulation of foreign material, infiltration of alveolar macrophages, septal cell hyperplasia, and granulomatous and chronic inflammation. Pigment was still present in basic chromium sulphate-treated animals after the 13-week recovery period, with partial recovery of the pathological lesions. An NOAEC for effects on lung was not established; The LOAEC for basic chromium sulphate was 17 mg/m³. This is equivalent to 21 mg/m³ basic chromium(III) acetate monohydrate.

These effects can be considered as local effects on the respiratory tract. Substance-related systemic effects were not observed. The observed organ weights effects can be considered secondary to the stress imposed on the respiratory tract and the resulting impairment of body weight gain. Therefore, the systemic NOAEC is 210 mg/m³.

A subchronic dermal study is not deemed necessary, since the dermal absorption of Cr(III) salts can be predicted to be very low, judging from the very low (<1%) gastrointestinal absorption and the lack of acute percutaneous toxicity. Because of the skin-sensitizing properties of basic Cr acetate, skin contact must be avoided by wearing appropriate protective clothing. As a result, dermal exposure will be insignificant.

The oral NOAEL can be extrapolated to the dermal route, since dermal absorption is expected to be in the same order of magnitude as oral absorption (<1%).

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

The selected study is the most adequate and reliable study with the longest duration and the lowest dose descriptor.

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

There is only one study available.

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

There is only one study available.

Justification for classification or non-classification

The available data on repeated dose toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.