Ethanone, 1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)thio]-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jun 2006 to Oct 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

469-300-0

EC Name:

-

Cas Number:

63675-73-0

Molecular formula:

Hill Empirical Formula: C16H16O3S CAS Empirical Formula: C16H16O3S

IUPAC Name:

1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)sulfanyl]ethan-1-one

Test material form:

solid: particulate/powder

Details on test material:

Lot no: 151105Purity - 101.39%

Test animals

Species:

rat

Strain:

other: HsdRccHan:WIST strain (nulliparous, non-pregnant)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female (nulliparous, non-pregnant) rats of the HsdRccHan:WIST strain were obtained from Harlan UK Lld, Bicester. All animals were given a clinical inspection for ill health on arrival and a sample was weighed.Preliminary testThe Study Director selected a dosing regimen that was intended either to demonstrate that the maximum dose level was unlikely to be lethal in the main study, or to determine a broad range of d ose levels that included the acute median lethal dose. The maximum dose level did not exceed 2000 mg/kg; the "limit test" dose level specified in the test guidelines. A pair of animals (one male and one female) received a single dermal dose of test article at 2000 mg/kg.Main study - limit testSince no compound-related mortality occurred in the preliminary test, one group of five male and five female rats was subjected to single dermal application of the test article at 2000 mg/kg. This group consisted of the two animals used in the preliminary test plus a further four male and four female rats to give the required group size of five males and five females.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

The test article was applied as a moistened powder to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

Duration of exposure:

24 h

Doses:

2000mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

Male and female (nulliparous, non-pregnant) rats of the HsdRccHan:WIST strain were obtained from Harlan UK Lld, Bicester. All animals were given a clinical inspection for ill health on arrival and a sample was weighed.

Results and discussion

Preliminary study:

The Study Director selected a dosing regimen that was intended either to demonstrate that the maximum dose level was unlikely to be lethal in the main study, or to determine a broad range of dose levels that included the acute median lethal dose. The maximum dose level did not exceed 2000 mg/kg; the "limit test" dose level specified in the test guidelines. A pair of animals (one male and one female) received a single dermal dose of test article at 2000 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: No clinical signs of reaction to treatment.

Gross pathology:

Effects on organs: None

Other findings:

Signs of toxicity (local):No clinical signs of reaction to treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal dermal dose or Beta Ketosulfide to rats was found to exceed 2000 mg/kg.The test material was considered to have no significant acute toxic risk in respect or its acute dermal toxicity and did not meet the criteria for classification according to EU labelling regulations Commission Regulation (EC) 1272/2008.

Executive summary:

This  study  was  conducted  to  assess  the  acute  dermal  toxicity  of  the  test  article,  BetaKetosulfide following a single (24hour) semi-occluded topical application to the rat.

The test article was applied as a moistened powder to the clipped dorsum of a group of five male and five female rats on Day1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated are as of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

No animal died and there were no clinica lsigns of reaction to treatment.No overt dermal changes were noted at the test site following a single application at 2000mg/kg. All rats achieved bodyweight gains during the study period. Macroscopic changes noted during necropsy of rat skilled on Day 15 were confined to a red area on the test site in one male and red foci on the lungs of one other male.However, it was considered that these were unlikely to be treatment related.

The acute median lethal dermal dose of Beta Ketosulfide to rats was found to exceed 2000mg/kg. The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria forclassification according to EU labelling regulations Commission Regulation (EC) 1272/2008.