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title	Study 123, Report Table (for reference only, will be deleted?)

For the purposes of team review of the example data, the report is included in this section:

Sample data #1: Determination of the in vitro genotoxicity potential of 10 tobacco products in the in vitro Micronucleus Assay

Study info: This study was performed to assess the in vitro genotoxicity of 10 different tobacco products containing 1% to 2% nicotine. The genotoxic potential was determined using the in vitro micronucleus test with TK6 lymphoblastoid suspension cells. The study was conducted in compliance with the following documents:

OECD TG 487 (2010): Guideline for the testing of chemicals: In vitro mammalian cell micronucleus test.
BL SOP 132: Determination of the in vitro genotoxicity of condensates from tobacco products and ingredients for tobacco products / electronic vapour products – in vitro micronucleus test (IVM) with TK6 cells.

The cells were exposed to increasing dose levels of tobacco product using short term treatment in the presence and absence of an external metabolic activation system (ST+/-S9 mix) as well as a long term treatment in the absence of an external metabolic activation system (LT-S9 mix).

Toxicity was calculated as relative increase in cell count (RICC), relative cell count (RCC) and relative population doubling (RPD). RPD is the cytotoxicity measure used for the assessment. RICC and RCC are also reported but not considered for the assessment.

Note: OECD GUIDELINE FOR THE TESTING OF CHEMICALS

Population Doubling = [log (Post-treatment cell number ÷ Initial cell number)] ÷ log 2

Conclusion: All tobacco product evaluated did not induce any signs of severe toxicity or genotoxicity in any of the treatments and do not fulfil the criteria to be classified as genotoxic.

Reported results: (only listed the result of one tobacco product as an example)

Statistical analysis

Adjusted p-values calculated for the micronucleus frequencies for every dose level as compared to the corresponding solvent control after ST in the presence and absence of S9 mix as well as LT in the absence of S9 mix. One way ANOVA with posthoc Dunnett’s test for multiple comparisons for the dose response and a two tailed unpaired student’s t-test for the comparison of positive and negative control were used. The difference between the samples is considered statistically significant at p≤0.05.

Treatment	Test date	Concentration [µg/ml]	Fold increase of MN over background	Adjusted p- value	Significant increase Y/N
ST+ S9	25.05.2022	1250	0.9	0.9973	N
		2500	0.9	0.9517	N
		3750	0.6	0.2654	N
		5000	0.9	0.9895	N
		CPA [5µg/ml]	3.1	0.0003	Y
ST-S9	25.05.2022	1250	1.6	0.6408	N
		2500	1.3	0.8995	N
		3750	2.9	0.0106	N
		5000	1.0	> 0.9999	N
		Bleo [0.2µg/ml]	3.8	0.0002	Y
LT-S9	25.05.2022	1250	0.7	0.5958	N
		2500	1.3	0.6378	N
		3750	0.5	0.1146	N
		5000	1.1	0.9929	N
		Bleo [0.5µg/ml]	2.9	0.0047	Y

Bleo: Bleomycin; CPA: Cyclophosphamid A; statistically significant increases are highlighted in bold.

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title	Study 123, Raw data (for reference only, will be deleted?)

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title	ts.xpt (trial summary, study level parameters)

Assumption: The intent of this dataset is to provide a summary of trial (study) information. This is not subject-level data.
Assumption: A Trial (study) can have more than one assay type
Assumption: ASSAYID value of ALL indicates that it applies to all assays in the study
This example currently shows SPDEVID and DUREFID in BOTH the TS domain and the TX domain, but we should discuss if this should only ever be in TX (with the same value for all sets if there is only one device used)
Assumption: SPDEVID (sponsor defined device identifier) should be added at the trial set level (tx.xpt) - we can discuss if this should be in TS when there is only one device for a study
- This allows for studies where there are multiple products and different product(s) per trial set, one record for each product that is being tested in each particular trial set (tx.xpt)

Row	STUDYID	ASSAYID	DOMAIN	TSSEQ	TSGRPID	TSPARMCD	TSPARM	TSVAL	TSVALNF
1	123	MNvit	TS	1		GLPTYP	Good Laboratory Practice Type	FDA
2	123	MNvit	TS	2		GLPTYP	Good Laboratory Practice Type	OECD
3	123	MNvit	TS	1		STSTDTC	Study Start Date	2022-05-25
4	123	MNvit	TS	1		STITLE	Study Title	Determination of the in vitro genotoxicity potential of 10 tobacco products in the in vitro Micronucleus Assay
5	123	MNvit	TS	1		SNDIGVER	SEND Implementation Guide Version	TOBACCO IMPLEMENTATION GUIDE VERSION 1.0
6	123	MNvit	TS	1		SNDCTVER	SEND Controlled Terminology Version	SEND Terminology 2021-09-30
7	123	MNvit	TS	1		SSPONSOR	Sponsor Organization	Example Sponsor Inc.
8	123	MNvit	TS	1		SPREFID	Sponsor's Study Reference ID		NOT APPLICABLE
9	123	MNvit	TS	1	1	TSTFNAM	Test Facility Name	Example Tox Lab Name
10	123	MNvit	TS	1	1	TSTFLOC	Test Facility Location	10 Somewhere Street, Montgomery, AL 10000
11	123	MNvit	TS	1	1	TFCNTRY	Test Facility Country	USA
12	123	MNvit	TS	1	1	STDIR	Study Director	Dr. R. Smith
13	123	MNvit	TS	1		GLPFL	GLP Flag	Y
14	123	MNvit	TS	1		ASTD	Assay Standard	OECD Test No. 487
15	123	MNvit	TS	1		ASTDV	Assay Standard Version	2016-07-29
16	123	MNvit	TS	1		SSTYP	Study Type	GENOTOXICITY IN VITRO
17	123	MNvit	TS	1		SSSTYP	Study Sub Type	In Vitro Micronucleus
18	123	MNvit	TS	1		SPECIES	Species	Homo Sapiens
19	123	MNvit	TS	1		??	Test System?	TK6 Lymphoblastoid Suspension Cells
20	123	MNvit	TS	1		SPDEVID	Sponsor defined device identifier	PUFFMASTER3K
21	123	MNvit	TS	1		DUREFID	Smoke Regimen	Medium Intensity Regimen

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title	tx.xpt (trial sets)

During CT definition/reviews will decide appropriate TXPARM and TXVAL; Treatment duration may be controlled; For now, we just include good example values based on our experience
Assumption: The Trial Sets (TX) domain provides the list of distinct sets of subjects having different experimental factors, treatment factors, inherent characteristics, or distinct sponsor designations as specified in the trial design.
Where is TK6 cell type? is this test system (see below)
- needs to be allowed to vary down to the well level / result level

A1:

A2:

Row	STUDYID	ASSAYID	DOMAIN	SETCD	SET (what sponsor calls it)	TXSEQ	TXPARMCD	TXPARM	TXVAL
	123	MNvit	TX	A1 (table 1, row 1, ST exposure with S9)	ST+S9		METACT	Metabolic Activation (this is the type of activation used)	+S9
	123	MNvit	TX	A1	ST+S9		METACTFL	Y/N presence of metabolic activation (this indicates that metabolic activation was used)
	123	MNvit	TX	A1	ST+S9		TRTDRTRG	Treatment Duration target. (how do we show 3-6 hour range? start/end, target and tolerance?, one text field not-analyzable)	3
	123	MNvit	TX	A1	ST+S9		TRTDRTOL	Treatment Duration Tolerance
	123	MNvit	TX	A1	ST+S9		TRTDURU	Treatment Duration Unit (this is for both TRTDURT, TRTDURTOL)	H
	123	MNvit	TX	A1	ST+S9		INTRVN	name of the intervention article (Tobacco ProdA, Bleomycin or Cyclophosphamid A)	Tobacco ProdA
	123	MNvit	TX	A1	ST+S9		ITVTYPE	type of intervention article choices of values: product; negative control; positive control	Product
	123	MNvit	TX	A1	ST+S9		ITVCONC	Concentration of intervention article	0
	123	MNvit	TX	A1	ST+S9		ITVCONCU	Concentration Unit	ug/ml
	123	MNvit	TS	A1	ST+S9	SPDEVID	Sponsor defined device identifier	PUFFMASTER3K
	123	MNvit	TS	A1	ST+S9	DUREFID	Smoke Regimen	Medium Intensity Regimen
	123	MNvit	TX	A2 (table 1, row 2)			METACT	Metabolic Activation (should there be two parms? Presence, type)?	+S9
	123	MNvit	TX	A2			TRTDRTRG	Treatment Duration target. (how do we show 3-6 hour range? start/end, target and tolerance?, one text field not-analyzable)	3
	123	MNvit	TX	A2			TRTDRTOL	Treatment Duration Tolerance
	123	MNvit	TX	A2			TRTDURU	Treatment Duration Unit (this is for both TRTDURT, TRTDURTOL)	H
	123	MNvit	TX	A2			INTRVN	name of the intervention article	Tobacco ProdA
	123	MNvit	TX	A2			ITVTYPE	type of intervention article	Product
	123	MNvit	TX	A2			ITVCONC	Concentration of i a	1250
	123	MNvit	TX	A2			ITVCONCU	Concentration Unit	ug/ml
	123	MNvit	TS	A2		SPDEVID	Sponsor defined device identifier	PUFFMASTER2023
	123	MNvit	TS	A2		DUREFID	Smoke Regimen	High Intensity Regimen
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Key

SET (what sponsor calls it)