Registration Dossier

Read-across from analogue:

Oral acute toxicity: LD50 > 2000 mg/kg bw , key study with 6 female rats according to OECD Test Guideline 423.

Dermal acute toxicity: LD50 > 2000 mg/kg bw, extrapolation from oral data.

Inhalation acute toxicity: LC50 > 50 mg/l, extrapolation from oral data.

Reference

Endpoint:: acute toxicity: oral
Type of information:: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:: key study
Justification for type of information:: REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH: The analogue approach covers the substance Ultramarine Blue (EC nº 701-340-9) and the substance Ultramarine Violet (EC nº 701-186-2).The analogue Ultramarine Blue shares the same structure (Sodalite-type structure (SOD-Zeolite)) with the substance Ultramarine Violet. Therefore, they are expected to be toxicologically equivalent.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES) Ultramarine blue, C.I. Pigment blue 29, EC number: 701-340-9;
Ultramarine Violet, C.I. Pigment Violet 15, EC number: 701-186-2.
No relevant impurities.
3. ANALOGUE APPROACH JUSTIFICATION: The analogue approach covers the substance Ultramarine Blue (EC nº 701-340-9) and the substance Ultramarine Violet (EC nº 701-186-2).The analogue Ultramarine Blue shares the same structure (Sodalite-type structure (SOD-Zeolite)) with the substance Ultramarine Violet. Therefore, they are expected to be toxicologically equivalent.
4. DATA MATRIX (Please, see attached document "Reporting Format for the analogue approach")
Reason / purpose for cross-reference:: read-across source
: Key result
Sex:: female
Dose descriptor:: LD50
Effect level:: > 2 000 mg/kg bw
Based on:: test mat.
Interpretation of results:: other: Not classified.
Remarks:: Criteria used for interpretation of results: EU. According to GHS criteria the test item could be classified in the Category 5 or as " GHS criteria not met", further information is needed regarding acute oral toxicity taking 5000mg/kg bw
Conclusions:: Based on the experimental results obtained with the analogue, the read-across approach is applied and the LD50 for substance Ultramarine Violet is considered to be greater than 2000 mg/kg bw.
Executive summary:: Based on the experimental results obtained with the analogue, the read-across approach is applied and the LD50 for substance Ultramarine Violet is considered to be greater than 2000 mg/kg bw.

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: extrapolation from results obtained by the oral route

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Principles of method if other than guideline:

Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.

Key result

Dose descriptor:

LC50

Effect level:

> 50 mg/L air

Based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals, an extrapolation based on the acute oral toxicity data is calculated for the inhalation route.

From the available data on two acute oral toxicity studies, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw (study 1: no mortality was observed) and greater from 10000 mg/kg bw (study 2: mortality was observed). As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 100% of an orally administered dose is systemically available. Since no data is available on inhalation absorption, the most precautionary default would be to assume 100% absorption by this route.

Based on this acute oral toxicity data, an oral NOAEL may be identified as greater than 10000 mg/kg bw. This NOAEL can be modified into an inhalation NOAEL using a route-to-route extrapolation based on the assumptions stated above. Taking into account an exposure of 4 hours for the acute inhalation toxicity study, the value of the oral LD50 is divided by the default physiological parameter under the allometric scaling principle which is approximately 0.2 m3/kg bw for rats. This extrapolation leads to a value of 10 mg/l (study 1) and 50 mg/l (study 2). Therefore, the 4 -h LC50 would be greater than 10 -50 mg/l.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the assumptions for the extrapolation from the acute oral toxicity data, the 4 -h LC50 would be greater than 10-50 mg/l.

Executive summary:

From the available data on two acute oral toxicity studies, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw (study 1: no mortality was observed) and greater from 10000 mg/kg bw (study 2: mortality was observed). As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 100% of an orally administered dose is systemically available. Since no data is available on inhalation absorption, the most precautionary default would be to assume 100% absorption by this route.

Based on this acute oral toxicity data, an oral NOAEL may be identified as greater than 10000 mg/kg bw. This NOAEL can be modified into an inhalation NOAEL using a route-to-route extrapolation based on the assumptions stated above. Taking into account an exposure of 4 hours for the acute inhalation toxicity study, the value of the oral LD50 is divided by the default physiological parameter under the allometric scaling principle which is approximately 0.2 m3/kg bw for rats. This extrapolation leads to a value of 10 mg/l (study 1) and 50 mg/l (study 2). Therefore, the 4 -h LC50 would be greater than 10 -50 mg/l.

Reference

Endpoint:: acute toxicity: dermal
Type of information:: other: extrapolation from results obtained by the oral route
Adequacy of study:: key study
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: other: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Principles of method if other than guideline:: Extrapolation based on available guidelines on route-to-route extrapolation of toxicity data when assessing health risks of chemicals.
Dose descriptor:: LD50
Effect level:: > 1 000 mg/kg bw
: Key result
Dose descriptor:: LD50
Effect level:: > 5 000 mg/kg bw
Interpretation of results:: GHS criteria not met
Conclusions:: Based on the assumptions for the extrapolation from the acute oral toxicity data, the dermal LD50 would be greater than 1000 mg/kg bw (study 1) and greater than 5000 mg/kg bw (study 2).
Executive summary:: From the available data on two acute oral toxicity studies, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw (study 1: no mortality was observed) and greater from 10000 mg/kg bw (study 2: mortality was observed). As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 1000 mg/kg bw (study 1) and greater than 5000 mg/kg bw (study 2).

Read-across from analogue:

Oral acute toxicity:

Key study: Study with 6 female rats (2 groups with 3 female rats per group) in a single dose oral toxicity test at 2000 mg/kg bw.

OECD Test Guideline 423.

The result was as follows: LD50 >2000 mg/kg bw.

Dermal acute toxicity:

Key study: Extrapolation from oral data.

From the available data on two acute oral toxicity studies, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw (study 1: no mortality was observed) and greater from 10000 mg/kg bw (study 2: mortality was observed). As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 50% of an orally administered dose is systemically available. Since no data is available on skin absorption, the most precautionary default would be to assume 100% absorption by this route although in reality very few substances will cross the skin to this extent. Therefore, based on these assumptions, the dermal LD50 would be greater than 1000 mg/kg bw (study 1) and greater than 5000 mg/kg bw (study 2).

Inhalation acute toxicity:

Key study: Extrapolation from oral data.

From the available data on two acute oral toxicity studies, it is concluded that the oral LD50 for the substance is greater than 2000 mg/kg bw (study 1: no mortality was observed) and greater from 10000 mg/kg bw (study 2: mortality was observed). As recommended in the corresponding guidelines, where data from the oral route is being used as the starting point, if no data are available on oral bioavailability, it is appropriate to assume that 100% of an orally administered dose is systemically available. Since no data is available on inhalation absorption, the most precautionary default would be to assume 100% absorption by this route.

Based on this acute oral toxicity data, an oral NOAEL may be identified as greater than 10000 mg/kg bw. This NOAEL can be modified into an inhalation NOAEL using a route-to-route extrapolation based on the assumptions stated above. Taking into account an exposure of 4 hours for the acute inhalation toxicity study, the value of the oral LD50 is divided by the default physiological parameter under the allometric scaling principle which is approximately 0.2 m3/kg bw for rats. This extrapolation leads to a value of 10 mg/l (study 1) and 50 mg/l (study 2). Therefore, the 4 -h LC50 would be greater than 10 -50 mg/l.

Oral acute toxicity LD50> 2000 mg/kg: not classified.

Dermal acute toxicity LD50> 2000 mg/kg: not classified.

Inhalation acute toxicity LC50 > 10 -50 mg/l: not classified (inhalation of dusts)