Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING

The screening for reproductive / developmental toxicity required at REACH Annex VIII level has been waived based on the following elements:

1. An OECD 422 study (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test) using Bisphenol AF (CAS 1478-61-1), the main constituent of the XA-31 reaction mass, is publicly available from Japanese Authorities (see details in attached justification). The study is summarized as follows:
“The oral administration of 4,4’-(1,1,1,3,3,3-Hexafluoropropane-2,2-diyl) diphenol [Bisphenol AF] to rats for a period of up to fifty-five days (including two weeks pre-mating, gestation and early lactation period for females) at dose levels of up to 300 mg/kg/day resulted in treatment-related changes at all dose levels.
For male animals, a ‘No Observed Adverse Effect Level’ (NOAEL) could not be established because of the microscopic changes in the mammary gland at all treatment levels, infertility at 300 mg/kg/day and reduced fertility at 100 and 30 mg/kg/day.
For female animals treated with 300 mg/kg/day, pregnancy was not achieved. For parental females, a NOAEL for systemic toxicity was achieved at 30 mg/kg/day because effects at 30 mg/kg/day were not considered to represent an adverse health effect for systemic toxicity. A NOAEL was not achieved for reproductive toxicity because of reduced pregnancy rates for parental females treated with 100 and 30 mg/kg/day compared to parental females from the control group.
For F1 offspring, the ‘No Observed Effect Level’ (NOEL) and NOAEL was 100 mg/kg/day under these test conditions.”

2. In the OECD 407 study (Repeated Dose 28-day Oral Toxicity Study in Rodents) on XA-31, histopathological findings were observed in the genital organs. Treatment-related atrophy of prostate, seminal vesicles and/or coagulating glands were seen in males at > 300 mg/kg/d. Potentially treatment related mild spermatid retention, minimal atrophy of Leydig cells and minimal tubular atrophy were seen in an isolated male given 1000 mg/kg/d. Also potentially treatment related feminization of mammary glands was observed at 1000 mg/kg/d. Given the design of the study and their nature and incidence, such findings are not sufficient for triggering classification, but are indicative of potential reproductive / developmental effects. Effects of the Bisphenol AF constituent on the testis in vivo are described in the scientific literature (see details in attached justification).

Together with animal welfare considerations and an effort in reducing testing in vertebrates, the performance of a screening for reproductive / developmental toxicity study at this tonnage level is not considered to be relevant.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion