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Effects on fertility

Description of key information

There is no study available of the type "screening for reproductive / developmental toxicity" which is an information requirement for the tonnage band 10-100 t/year (REACH, Annex VIII) and also for 100-1000 t/year (REACH, Annex IX). However, according to REACH Annex VIII, 8.7.1, Column 2, such information does not need to be provided if a pre-natal developmental is available.

Such pre-natal developmental toxicity data has been provided in the dossier (see under "Effects on developmental toxicity" and under "7.8.2 Developmental toxicity / teratogenicity" of the IUCLID data set). The data is on the read-across substance 2,4 -pentanedione (CAS No 123 -54 -6) and a thorough justification for this read-across approach is provided in IUCLID section 13.

Furthermore is pointed out concerning information requirements:

According to Reach Regulation Annex IX column 1, 8.7.3, a two generation test for the endpoint reproductive toxicity should be performed if effects on the reproductive organs were observed in subacute or subchronic tests. For the read-across substance 2,4-Pentanedione no statistically significant adverse effects on reproductive organs were observed after repeated exposure. In a subchronic inhalation toxicity study (5 d/week, 6 h/d) with acetylacetone conducted in male and female F344 rats with exposure concentrations of 0, 100, 300 and 650 ppm key reproductive organs (testes, epididymis, uterus, cervix and ovaries) were examined. Changes to reproductive organs were observed in individual animals but without statistical significance and biological relevance when compared to control animals. One animal of the control and one of the 300 ppm group had non-significant changes in the uterus size. One animal of the 300 ppm dose group had non-significant size changes in the cervix. After 4-week recovery phase one control animal showed epididymitis while in two females of the control group ovarial cysts were found. As none of these effects is of biological relevance it is concluded that after study termination and also after the four week recovery period no adverse effects on male and female reproductive organs were found.

In conclusion no adverse effects on reproductive organs are expected for the read-across substance 2,4-Pentanedione based on the available subacute and subchronic data on 2,4-Pentanedione. In accordance with REACH Regulation Annex IX column 1, 8.7.3, it is therefore not necessary to provide data from a two generation test (OECD 416) or an extended one generations test (OECD 443) as a surrogate.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Information and comment given by the previous lead registrant:

No developmental study is available on the registered substance. There is an inhalation developmental study on the read-across substance, 2,4 -pentanedione CAS# 123 -54 -6. However the source of the data is from a published literature article with only limited information (see endpoint study record). However the effects reported do not appear to be sufficient for classification. Fetotoxic effects (reduced fetal weights in male fetuses) were observed at 200 ppm without signs of maternal toxicity. In addition, at 400 ppm (reduced fetal weights in fetuses of both sexes and reduced fetal ossification) reduced maternal weight also occurs.

Comment of the present lead registrant to these statements:

The present lead registrant agrees to the above given statements except for these points:

The published literature article is regarded as a meaningful source of information. It contains all essential information from the conducted study.

Furthermore, to be precise on concentrations: Fetotoxic effects (reduced fetal weights in male fetuses) were observed at 202 ppm without signs of maternal toxicity. In addition, at 398 ppm (reduced fetal weights in fetuses of both sexes and reduced fetal ossification) reduced maternal weight also occurs.

The lowest NOAEC (with no effect on fetal weights) can thus be determined as 217 mg/m3 (information in literature article of Tyl et al 1990: 53 ppm of 2,4-pentanedione).

The NOAEC for maternal animals can be pointed out as 827 mg/m3 (Tyl et al.1990, p 470: for maternal animals, very slight, nonstatistically significant, reduction in body weights at 202 ppm).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
217 mg/m³
Species:
rat
Quality of whole database:
Equivalent or similar to OECD Guideline 414 Prenatal Developmental Toxicity Study. Fetal weight is basis for NOAEC.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data C&L for this endpoint is not warranted. The results are regarded as conclusive but not sufficient for classification.