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Administrative data

Description of key information

A sub-chronic oral toxicity study (90-day) revealed a NOAEL of 450 mg/kg bw/day, and a LOAEL of 1000 mg/kg bw/day. In one dermal repeated dose toxicity study (21 days) a NOAEL of 360 mg/kg bw/day (highest concentration tested) was obtained with the rabbit. Applying route to route extrapolation, by assuming that penetration of BMDBM through skin is equal to penetration through the intestinal wall, the same effect levels as for oral route shall apply for the dermal route of exposure. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
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
Dose descriptor:
LOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
6.6 mg/cm²
Study duration:
subacute
Species:
rabbit
Quality of whole database:
Spiers and Candas, J Appl Physiol. 1984 Jan;56(1):240-3: Skin surface area (Ab) of rat inrelation to mass m is Ab = 6.88m^0.736. 300 g average weight for rats was assumed.

Additional information

One subchronic oral study on BMDBM toxicity is available. In this study, the only noteworthy effect is a concentration dependent increase in liver weight which was mainly attributed to be due to adaption to xenobiotic treatment. Nevertheless, increase in liver weight became significant at 450 mg/kg bw/day in females and at 1000 mg/kg bw/day in both sexes. Furthermore, in the 1000 mg/kg bw/day females, reduced RBC and Hb values were noted. Therefore, the NOAEL (rat, oral) was considered to be 450 mg/kg bw/day and the LOAEL to be 1000 mg/kg bw/day.

In one subacute dermal toxicity studies on butyl methoxydibenzoylmethane (BMDBM), which were conducted on rabbits, no systemic toxicity was noticed up to the highest tested concentration of 360 mg/kg bw/day. Applying route to route extrapolation, by assuming that penetration of BMDBM through skin is equal to penetration through the intestinal wall, the same effect levels as for oral route shall apply for the dermal route of exposure. Concerning local effects, in the rabbit study (Keller 1980), concentration-dependent increase of erythema and edema formation was noticed after dermal application.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Comparable to guideline study under GLP.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Comparable to guideline study with acceptable restrictions.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: hematopoiesis; digestive: liver

Justification for classification or non-classification

Based on a LOEAL of 1000 mg/kg bw/d derived from an oral subchronic toxicity study with the rat, BMDBM is not to be classified for its repeated dose toxicity properties. This finding is backed up by dermal subacute toxicity studies, where NOAELs have been observed up to the highest tested dose levels of 230 and 370 mg/kg bw/d, respectively.