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Administrative data

Description of key information

Oral:

Currently no repeated dose toxicity study via oral route with Reactive Blue 072 is available. However, a study with source substance FAT 40336/B is available. In this subacute 28-day toxicity study, FAT 40336/B was administered daily by gavage to SPF-bred Wistar rats. The study was comprised of four groups. In this study, individuals of both test groups (200 and 1000 mg/kg bw/day) showed bluish to greenish discoloration of various organs, but no other treatment-related abnormalities occurred. Oral administration of FAT 40'336/B to rats for 28 days at the dose level of 1000 mg/kg bw/day produced no toxicological, hematological, biochemical or pathological evidence of toxicity. Based upon the results obtained in this study, the "no-adverse-effect-level" of FAT 40'336/B is 1000 mg/kg bw/day for male and female rats when administered orally by gavage for a period of 28 days.

Inhalation:

Currently no study to assess the repeated dose inhalation toxicity potential of Reactive Blue 72 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>350 °C). Hence the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Further the chemical is found to have water solubility of 376 g/L, hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared by the cilia present in the respiratory tract, thereby further limiting the absorption. No systemic toxicity was observed when Reactive Blue 072 was administered upto 1000 mg/kg bw/day via gavage in a reproductive/developmental toxicity screening study. Further, no systemic toxicity was reported in a 28-day repeated dose toxicity study with source substance FAT 40336/B. Taking into consideration the above arguments, low toxicity potential is expected on repeated exposure of Reactive Blue 72 via inhalation route and safety for human health can be estimated using the principles of route to route extrapolation. Hence, the conduct of repeated dose toxicity study via inhalation route for Reactive Blue 072 is considered to be scientifically not necessary.

Dermal:

Currently no study to assess the repeated dose dermal toxicity of Reactive Blue 072 is available. However, the molecular weight of the chemical is 1194.05 g/mol (theoretical structure), indicating it being too large for dermal absorption. It has water solubility of 376 g/L and n-octanol/water partition coefficient (log P) of -5.33, indicating it beingtoo hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance will be low.No systemic toxicity was observed when Reactive Blue 072 was administered upto 1000 mg/kg bw/day via gavage in a reproductive/developmental toxicity screening study. Further, no systemic toxicity was reported in a 28-day repeated dose toxicity study with source substance FAT 40336/B. Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Taking into consideration the above arguments, low toxicity potential is expected on repeated exposure of Reactive Blue 72 via dermal route and safety for human health can be estimated using the principles of route to route extrapolation. Hence, the conduct of repeated dose toxicity study via dermal route for Reactive Blue 072 is considered to be scientifically not necessary.

Reactive Blue 72 is considered to have a NOAEL of 1000 mg/kg bw/day.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer chapter 13 for detailed read across justification.
Reason / purpose for cross-reference:
read-across source
Control animals:
not specified
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: no adverse effects were seen
Critical effects observed:
not specified
Conclusions:
The "no-observed-adverse-effect-level" of structurally similar substance, FAT 40'336/B is 1000 mg/kg body weight for male and female rats when administered orally by gavage for a period of 28 days.
Executive summary:

Currently no repeated dose toxicity study via oral route with Reactive Blue 072 is available. However, a study with structurally similar substance FAT 40336/B is available. In this subacute 28-day toxicity study, FAT 40'336/B was administered daily by gavage to SPF-bred Wistar rats. The study was comprised of four groups.

The dose levels used in this study are based on data from acute studies and the conclusions drawn from a 5-day oral toxicity (range-finding) study (RCC Project 223694). In this study, individuals of both test groups (200 and 1000 mg test article per kg body weight) showed bluish to greenish discoloration of various organs, but no other treatment-related abnormalities occurred.

Based upon the results obtained in this study, the "no-adverse-effect-level" of FAT 40'336/B is 1000 mg/kg body weight for male and female rats when administered orally by gavage for a period of 28 days. Oral administration of FAT 40'336/B to rats for 28 days at the dose level of 1000 mg/kg body weight/day produced no toxicological, hematological, biochemical or pathological evidence of toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
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

Justification for classification or non-classification

Currently no repeated dose toxicity study with Reactive Blue 72 is available. However, structurally similar substance FAT 40336/B did not cause systemic toxicity in a subacute 28-day toxicity study via oral route. Hence, Reactive Blue 72 does not warrant classification as per the Regulation (EC) No. 1272/2008.