[No public or meaningful name is available]

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a sub-chronic toxicity study (90 days) does not need to be conducted because a reliable chronic toxicity study is available, conducted with an appropriate species and route of administration

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to Annex IX, section 8.6.2, column 2 of Regulation No. 1907/2006, repeated dose toxicity testing by the dermal route is appropriate if 1) inhalation of the substance is unlikely, 2) skin contact in production and/or use is likely and 3) one of the following conditions is met: toxicity is observed in the acute dermal toxicity test at lower doses than in the oral toxicity test; or, systemic effects or other evidence of absorption is observed in skin and/or eye irritation studies; or, in vitro tests indicate significant dermal absorption; or, significant dermal toxicity or dermal penetration is recognised for structurally-related substances. Although skin contact during production and use is possible, inhalation is expected to be the primary route of exposure. The substance is an inorganic ionic solid. It is expected to partition strongly to water rather than organic media. While it is not possible to measure or accurately predict an octanol/water partition coefficient for inorganic ionic substances, such a value would be expected to be very low. Electrolytes are also known not to penetrate the skin in any significant quantity. Given the physico-chemical properties of calcium carbonate (a component of the substance), it is not expected that the substance would penetrate the skin in any significant quantity and so would therefore not cause any toxic effects following repeated dermal exposure. Acute oral (Bradshaw, 2008) and dermal toxicity (Bradshaw, 2010) studies were performed in the rat using test concentrations of 2000 mg/kg of calcium carbonate and calcium carbonate (nano), respectively. No mortalities or signs of systemic toxicity were observed in either study and no irritation was observed in the dermal study. Hence, calcium carbonate is not acutely toxic via the oral and dermal routes. Furthermore, a 28 day repeat dose oral toxicity study in rats was performed according to OECD Guideline 422 and GLP with concentrations of calcium carbonate (nano) of 0, 100, 300 and 1000 mg/kg bw/day (Dunster, 2010). Treatment-related effects were observed at all dose levels. However, these effects were considered not to represent an adverse effect of treatment. Hence, the NOAEL for systemic toxicity was considered to be 1000 mg/kg bodyweight/day and calcium carbonate is not considered to be toxic following repeated oral exposure for a period of 28 days. In addition, there was no evidence of systemic toxicity or absorption of the test material observed in the skin irritation and eye irritation studies (Sanders, 2004). In a study similar to OECD 452 rats have received the test item silicic acid, calcium salt (read-across substance) via feed (1, 5, 7.5 and 10% nominal in diet). No difference in survival from the control and no gross signs of toxicity have been reported. In the highest dose group growth suppression and slightly elevated pH of the urine but no tumours have been observed. The NOEL is considered to be the 5% dietary level, which is estimated to correspond to about 2500 – 3200 mg/kg bw/day, based on reduction in body-weight gain and isolated cases of calculi and brittle in kidney and urinary bladder, respectively, as well as a few cases of cholangitis-like lesions at the higher dose levels (Columbia, 1956).
Based on this information, repeated dose toxicity studies via the dermal route are therefore scientifically unjustified also due to animal welfare reasons.

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified