3,4-dihydro-2H-1,4-benzoxazin-6-ol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to Regulation (EC) No 1907/2006, Annex VIII, 8.5.3, column 2 (specific rules for adaptation from column 1), testing by the dermal route is appropriate if:
1) inhalation of the substance is unlikely; and
2) skin contact in production and/or use is likely; and
3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin.
According to the results of the in vitro dermal absorption study (OECD TG Guideline 428), dermal absorption rate for hydroxybenzomorpholine was considered as 2.2%. Given the low and non-significant rate of absorption through skin of the substance, acute toxicity testing by the dermal route is not considered appropriate. However, skin contact may occur during worker manufacturing, formulation or consumer use.
Hydroxybenzomorpholine exhibited a low order of acute oral toxicity with an acute oral LD50 value between 1000 and 2000 mg/kg bw in male and female rats. Taking into consideration that dermal absorption rate for hydroxybenzomorpholine is 2.2% and by default that oral absorption is 50%, an extrapolation could be done by calculation
50% oral vs. 2.2% dermal = 50 :2.2 = 22.72
The LD50 demal for Hydroxybenzomorpholine could be calculated to be between 22 727 mg/kg bw/d and 45 440 mg/kg bw/d.
• 1000 mg/kg bw/d x 22.72 = 22 727 mg/kg bw/d
• 2000 mg/kg bw/d x 22.72 = 45 440 mg/kg bw/d
Hydroxybenzomorpholine is not expected to be acutely hazardous via the dermal route.
No further testing is required.