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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Additional information

There are no available data for this endpoint for CAS: 96152-43-1, therefore studies from supporting, structurally similar substances have been used as for read-across purposes to address this endpoint. The NOAEL is then adjusted for the presence of oil in the tested sample (50%) and the lack of this in the Registration material.

Oral

In the key study for reproductive toxicity, oral exposure (Nemec, 1995, report number: WIL-187006) the study was conducted according to OECD Guideline 416 (Two-Generation Reproduction Toxicity Study). The study was conducted in line with GLP.

The reliability rating for this study is 1, however this is being used as read across as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997. T

his was considered to be the most reliable and robust study and a full multigenerational study as opposed to a screening study. The NOAEL for reproductive toxicity for this study was 300mg/kg bw/day, which was reduced for the Registration material to 150mg/kg bw/day.

Supporting reproductive screening studies:

- The Lamb, 1993, reproductive toxicity, oral exposure study (report number: WIL-187001) was not considered the key study as it was conducted less recently than the above key study and was considered less robust than the above key study due to its nature as a screening study. This

study was conducted to the OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) and GLP.

The reliability rating for this study is 1, however this is being used as read across to a supporting substance and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997.

Based upon the results of this study, the apparent NOAEL (no observable adverse effect level) parental toxicity was considered to be 200 mg/kg/day. Equivocal prenatal toxicity was observed at a dose level of 200 mg/kg/day. The results of this screening study indicated that further toxicity testing for adverse reproductive effects should be considered. As such the OECD 416 study (key study) mentioned above was conducted..

- The Schroeder, 1998 study (Huntingdon Life Sciences report number: 96-4084) was

conducted according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test). The study was conducted in line with GLP.

The reliability rating for this study is 1, however this is being used as read across to a supporting substance as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997. Reproductive toxicity NOAEL = 1000 mg/kg b.wt./day for males and females, highest dose tested.


Short description of key information:
Oral:
Two-generation reproduction study - Based on the results of this study, a NOAEL (no observable adverse effect level) for systemic parental and neonatal toxicity was derived for the test substance. 300 mg/kg/day was also considered to be the NOAEL for reproductive toxicity. There was no evidence of cumulative toxic effect across generations in this study. TO account for the presence of oil in the tested sample (50%), and the lack of oil in the Registration material, the NOAEL was reduced to 150mg/kg bw/day. It is recognised that the oil is not likely to have an effect on reproductive performance and so this reduced NOAEL will be very conservative; the true value for the registration material is more likely to be close to or the same as that of the material in oil. However a precautionary approach has been taken throughout the dossier.

Justification for selection of Effect on fertility via oral route:
Decreased female fertility, prenatal toxicity (increased number of dead pups and reduced litter weight at birth), decreased maternal body weight gain during gestation, and decreased maternal food consumption during lactation. The NOAEL of 300mg/kg bw/day was reduced to account for the presence of oil to 150mg/kg bw /day

Effects on developmental toxicity

Description of key information
Oral:
Maternal toxicity (reduced body weight gain) was observed at the 1000 mg/kg/day dose level. No maternal toxicity was apparent at the 50 and 300 mg/kg/day dose levels. Developmental toxicity was apparent at a dose level of 1000 mg/kg/day by an increased incidence of the skeletal variant bent ribs. No developmental toxicity was observed at dose levels of 50 and 300 mg/kg/day.
Based on the results of this study, the NOAEL (no observable adverse effect level) for maternal and developmental toxicity was considered to be 300 mg/kg/day. This was then adjusted to account for the presence of oil in the tested samples and the lack in the Registration material, producing a NOAEL for the CSA of 150mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Additional information

There are no available data for this endpoint for CAS: 96152-43-1, therefore studies from supporting, structurally similar substances have been used for read-across purposes to address this endpoint. The NOAEL has been adjusted for the presence of oil.

Oral

- In the key study for Developmental toxicity, oral exposure (Nemec, 1994, report number: WIL-187005) the study was conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). The study was conducted in line with GLP.

The reliability rating for this study is 1, however this is being used as read across as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997.

Supporting developmental study:

- The Watson, 1990, developmental toxicity, oral exposure study (report number: CEHC 3086) was not considered the key study as it was conducted less recently than the above key study and had significant deviations from the guideline. The study was conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study) and GLP, however fewer than 20 gravid females per group and no laboratory historical control data was presented. A reliability rating of 2 according to the criteria of Klimisch, 1997 was assigned. The study is being used as read across to a structurally similar substance. Based upon the results of this study, the maternal no-observed-effect level (NOEL) was 300 mg/kg/day, and the developmental NOEL was 50 mg/kg/day. The developmental effects were not reflected in the key study at this dose level.


Justification for selection of Effect on developmental toxicity: via oral route:
Maternal toxicity (reduced body weight gain) was observed at the 1000 mg/kg/day dose level. No maternal toxicity was apparent at the 50 and 300 mg/kg/day dose levels. Developmental toxicity was apparent at a dose level of 1000 mg/kg/day by an increased incidence of the skeletal variant bent ribs. No developmental toxicity was observed at dose levels of 50 and 300 mg/kg/day. The NOAEL of 300mg/kg bw/day was reduced to account for the presence of oil to 150mg/kg bw /day
Based on the results of this study, the NOAEL (no observable adverse effect level) for maternal and developmental toxicity was considered to be 300 mg/kg/day. These values are then adjusted to account for the presence of oil (50%) in the tested samples to derive a NOAEL for the Registration material of 150mg/kg bw/day for developmental (and maternal) toxicity.

Justification for classification or non-classification

The results from the key study performed on a similar material within the Category which is being used as read-across to this Registration material, show effects on reproductive performance. These are considered most likely to be caused by the presence of a component of the Registration material which is classified as a Category 2 (DSD) or Category 1B (CLP) Reproductive toxin which is present at low levels in the Registration material. Hence the Registration material classification for this endpoint takes this into account and is classified accordingly (see Section 2).

Additional information

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