Registration Dossier

Administrative data

Description of key information

Repeated Dose Toxicity:- oral, rat, 42 days (OECD422): NOEL (males) = 1000 mg/kg bw/d, N/LOAEL (females) = 1000 mg/kg bw/d; based on reduced food consumption and decreased body weight change during gestation (BASF SE 2012); further old toxicological studies do not show a hazard.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

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

A subacute study was conducted according to OECD 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) and GLP (BASF SE 2012b; reliability score 1). The test substance was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0, 100, 300 and 1000 mg/kg bw/d. Drinking water served as vehicle. The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation period as well as 4 days of lactation and two weeks thereafter in females. A detailed clinical observation (DCO) was performed in all animals before initial test substance administration and, as a rule, thereafter at weekly intervals. Food consumption of the F0 parents was determined once weekly during premating. In dams food consumption was determined for gestation days 0 - 7, 7 - 14, 14 - 20 and lactation days 1 - 4. Body weights of F0 parents were determined once a week, in males throughout the study and in females during premating and mating. During gestation and lactation period, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, after the day of parturition (postnatal day [PND] 0) and on PND 4. Clinicochemical and hematological examinations as well as urinalyses were performed in 5 animals per sex and group towards the end of the administration period. Further, a functional observational battery was performed and motor activity was measured in 5 animals per sex and test group towards the end of the administration period. All F0 parental animals were sacrificed and assessed by gross pathology. Weights of selected organs were recorded and a histopathological examination was performed. In the highest test group significantly decreased (max. -13%) food consumption during the entire gestation period, decreased body weight changes during gestation days 0 to 7 (-20%) and slightly decreased body weight during the entire gestation were seen in female animals. No adverse effects were seen in clinical pathological and pathological examinations. The animals of the other two test groups and high dosed males did not show adverse effects. The NOEL for general, systemic toxicity was 300 mg/kg bw/d based on the slightly reduced food consumption and the interim decreased body weight change during the gestation at 1000 mg/kg bw/d.

In the pretest of the subacute study which was conducted for 14 days to assess if the Wistar rats tolerate the test substance at the offered dose levels, the test substance was administered by gavage to groups of 3 male and 3 female Wistar rats at dose levels of 0 (vehicle control; drinking water), 500 and 1000 mg/kg body weight/day (BASF SE 2011; reliability score 2). No guideline was followed and there was no GLP compliance as it was a pretest. Food consumption and water consumption were determined on study days 3, 7, 10 and 14. Body weight was determined before the start of the administration period in order to randomize the rats and on study days 0, 3, 7, 10 and 14. The rats were checked daily for any abnormal clinically signs before the administration as well as within 2 hours and within 5 hours after the administration. All rats were sacrificed, necropsied and assessed by gross pathology. As a result of the study, rats tolerate adequate amounts of the test substance by gavage up to 1000 mg/kg bw/d and no adverse effects were seen.

In 1961, a long-term study feeding study involving in-utero exposure in rats was performed at the University of Heidelberg, Germany (Nothdurft 1961). This study aims at carcinogenicity and only few parameters on general toxicity are reported. The robust study summary is maintained in the section of carcinogenicity. Nominal dieteray doses were 0.1 and 1%. The first generation was exposed for 6 months prior to mating. The offspring (20 males and 20 females) was exposed for 24 months. No adverse effects on survival rate, organ pathology or body weight were reported.

No adverse effects were reported in a subchronic feeding study with rats at 0.1% in the diet (Umeda 1956).

Putilina et al (1966) published investigations with rat and mice on an anthraquinone dye as well as a pigment in a russian journal. Both substances were applied by gavage using olive oil as vehicle. The information is not presented in a clear way. It appears that mice were treated for 30 days with a dose of 1000 mg/kg bw. Then also mice were treated or kept for six months with doses of 50 and 100 mg/kg bw. As what can be derived from the publication, effects on body weight gain were observed at 100 mg/kg bw, but it is not clear whether it refers to the dye or the pigment. The same is true for the effects on liver weight at 1000 mg/kg bw.

Overall, the available data does not give rise of concern for subchronic toxicity. The poor solubility in octanol shows that the bioaccumulation is not a problem and in general, all physico-chemical properties indicate absence or very systemic uptake.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. No adverse effects were observed at doses of less than 150 mg/kg bw. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC.

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No adverse effects were noted at doses of less than 300 mg/kg bw. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008.