Metabolomics as read-across tool: An example with 3-aminopropanol and 2-aminoethanol.

Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their 'Read-Across Assessment Framework' (RAAF, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants fail to reduce the level of 'remaining uncertainty' intrinsical to every read-across approach compared to testing a substance experimentally. Recently, the use of metabolomics to support read-across cases with biological information has been reported in a case study with phenoxy herbicides (Ravenzwaay et al., 2016). In the present case-study a 'weight-of-evidence' read-across approach from 2-aminoethanol (MEA = 'source') to 3-aminopropanol (3AP = 'target') with metabolomics as 'supporting evidence' reducing the remaining uncertainties is reported. We demonstrate the high structural similarity of the two analogous substances based on the available data and we report how metabolome data add confidence concerning mechanistic similarity in this read-across approach. Finally, the herein described read-across case supported by metabolomics is used to cover the data gaps in repeated dose and reproductive toxicity endpoint of 3AP via weight of evidence for the REACH-registration.

[Screening tests for gonorrhea in clinics for contraceptive advice]. / Förekomst av gonorré hos antikonceptionssökande kvinnor.

PIP: The Swedish Association for Sex Education tested 1556 women for gonorrhea. The women were 14-49 years of age and attended contraceptive clinics in Stockholm and Goteborg. Cultures were taken from the urethra, cervix, and rectum. 24 (1.5%) of the women had gonorrhea, of whom 23 were between 15-24. 21 of the 1023 unmarried women had positive gonorrhea tests. 16 of the 1137 women who used oral contraceptives had positive tests. Gonococci were found in 20 cervical tests, 11 urethral tests, and 6 rectal tests. 3 cases were diagnosed solely by the rectal tests. 11 of the 24 women had no symptoms, 6 pelvic afflictions, and 3 had urethral afflictions. In some cases men who had had sexual contact with the infected women were tested; 1 positive gonorrhea test was found among these men.^ieng