3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl methacrylate

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment. Although data provided have a report year after 2008, the study was performed to fulfill needs required by US regulators and/or for product stewardship purposes; therefore, the studies were not performed according to GLP. DuPont’s stewardship principle states that “We will adhere to the highest standards for the safe operation of facilities and the protection of our environment, our employees, our customers and the people of the communities in which we do business”. The study was carried out in the US in accordance with our internal Product Stewardship standard which is part of the American Chemical Council’s “Responsible Care Program”. This study was not performed to fulfill an information requirement under REACH, but since the test data were already available they were provided as part of the REACH submission.

Data source

Materials and methods

Objective of study:

other: half-life (T1/2), in vitro clearance (mL/hr), extrapolated in vivo clearance (mL/hr/kg), and metabolite ID

Principles of method if other than guideline:

The objective of the study was to estimate metabolic clearance of the test substance in rat hepatocytes, identify metabolites, and extrapolate results to the whole animal.

GLP compliance:

no

Test material

Radiolabelling:

no

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

other: in vitro

Details on exposure:

Rat hepatocytes were incubated with the test substance. Replicates per experiment included 3 test, 3 dead cell control, and 1 positive control. Clearance incubations were 5, 15, 30, 45, 60, 90, and 120 minutes. Biotransformation incubations were 10 and 30 minutes.

Positive control reference chemical:

4-nonylphenol

Details on study design:

See additional information on materials and methods.

Details on dosing and sampling:

See additional information on materials and methods.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Metabolites in male and female hepatocytes after 10 and 30 minutes were analogous to those observed for 6:2 FTOH in rat hepatocytes, with the exception of the glutathione adduct of the parent and the hydroxylated parent. The major metabolite was 6:2 uFTOH-GH. Additional major metabolites in rat hepatocytes included 6:2 GTOH-Gluc, 6:2 diOH-diGluc, 6:2 FTOH (by GC/MS), 6:2 FMA-GS (male hepatocytes only), 6:2 FTOH-Sulf (female hepatocytes only), and 6:2 UAL-GS (isomer II DNPH deriv.) (female hepatocytes only). 

Any other information on results incl. tables

Metabolites in male and female rat hepatocytes after 10 and 30 minutes

Hepatocyte metabolic Reaction From HPLC/MS	Observed MW (M-H)*	Retention Time (min)	Male (min)		Female (min)
			10	30	10	30
6:2 UA-GS (Isomer I)	458.0744	10.69	-	+	+	+
Unknown	741.0737	11.38	+	+	+	+
Unknown (Isomer I)	487.0855	11.41	+	+	+	+
Unknown (Isomer II)	487.0858	11.52	+	+	+	+
Unknown	785.0993	11.56	+	+	+	+
Unknown	712.0835	11.59	+	+	+	+
6:2 UA-GS (Isomer II)	644.0577	11.63	+	+	+	+
Unknown	626.0657	11.71	-	+	+	+
6:2 uFTOH-GS	630.0779	11.93	+	+++	+++	+++
6:2 UAL-GS	628.0634	12.00	+	+	+	+
6:2 Acid-GS	646.0731	12.05	+	+	+	+
Unknown	686.1044	12.10	+	++	+	++
6:2 diOH-diGluc	731.0711	11.98	+	++	+	++
Unknown	668.0933	12.50	+	++	+	++
Hydroxy-6:2 FTOH-Gluc	555.0337	12.53	+	+	+	+
Hydroxy 6:2 FMA-GS	754.1118	12.70	+	+	+	+
5-2 OH-Gluc	489.0423	12.79	-	+	-	+
6:2 FTOH-Gluc	539.0389	13.24	+++	++	+	++
6:2 FMA-GS	738.1157	13.33	++	++	+	+
6:2 FTOH-Sulf	442.9636	13.29	+	+	++	++
6:2 diOH (acetate adduct)	439.0228	14.63	+	+	-	+
6:2 UA-Cys	457.9931	14.73	-	+	-	-
6:2 uFTOH-Cys	444.0137	15.05	-	+	+	+
5-3 Acid	341.0047	15.21	+	+	+	+
6:2 UA	356.9797	15.41	+	+	+	+
6:2 Acid	376.9858	15.49	+	+	+	+
5-3 UA	338.9890	15.53	+	+	+	+
6:2 UAL-GS (Isomer I DNPH deriv.)	808.0909	13.79	+	+	+	+
6:2 UAL-GS (Isomer II DNPH deriv.)	808.0909	14.15	+	+	+	++
5-3 β-hydroxy UAL (DNPH deriv.)	519.0178	16.79	+	+	+	+
5-2 Ketone (DNPH deriv.)	491.0231	18.21	+	+	+	+
6:2 FTOH (by GC/MS)	363	7.42	++	++	++	++
6:2 FMA Parent (by GC/MS)	431	8.98	++	+	++	+

+++ Most intense metabolite

++ Major metabolite

+ Minor metabolite

- Not detected

* For male hepatocytes

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: The test substance was rapidly metabolised in live hepatocyte incubations.
T1/2 (min): Male = <3 min, Female = <3min
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

The objective of the study was to estimate metabolic clearance of the test substance in rat hepatocytes and to identify metabolites, and extrapolate results to the whole animal. The test substance is rapidly metabolised in live male and female hepatocyte incubations compared to heat-inactivated controls. A rate was not obtainable as there was less than 5% of parent remaining at the first time point at 5 minutes of incubation and no parent remaining by the second time point at 15 minutes. Therefore, T1/2 (min): Male <3 min, Female <3 min.