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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Suitable calculation method

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Executive summary:

Dermal absorption was demonstrated to be low by in silico modelling of dermal absorption (details see chapter 7.1). For humans, a penetration rate of 0.768 µg/cm²/hr is obtained.

In rats, an (on average) 10.9-fold higher skin absorption rate is anticipated (cf Lit: van Ravenzwaay & Leibold, 1984, see below) leading to 8.37 µg/cm²/hr

 

Standard conditions of acute dermal toxicity testing are adapted as follows: rat, weight 250 g, exposed skin surface (10 %): 20 cm²

 

This leads to a systemic burden of 167.4 µg/hr and 4018 µg in 24 hrs which is equivalent to16.1 mg/kg body weight in rats.

Compared to the LD50 value of 950 mg/kg and the LD0 value of 200 mg/kg obtained from the key study on acute oral toxicity in rats, any occurrence of acute toxicity by the dermal route is not expected.

Moreover, no signs of toxicity were reported in rabbits by 24 hr exposure to 380 mg/kg (see 7.2.3 ff).

Therefore, and for the sake of animal welfare, an additional animal test on dermal toxicity of N-methylol methacrylamide is not considered as justified.

 

Reference 

B. van Raavenzwaay, E. Leibold, A comparison between in vitro rat and human and in vivo rat skin absorption studies, Human Exp. Toxicol. 23 (2004), 421-430