Mono- and/or di- and/or tri(1-phenylethyl)-m-cresol and p-cresol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: this study was planned and executed in accordance with relevant guidelines as well as the requirements of the GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Few times during the quarantine air temperature exceeded 25 °C. It had no influence on the study course and results.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Atlen SK

IUPAC Name:

Atlen SK

Details on test material:

- Name of test material (as cited in study report): Atlen SK
- Substance type: organic, UVCB
- Physical state: liquid
- Lot/batch No.:2/3
- Expiration date of the lot/batch: 2009-06-06
- Stability under test conditions: stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: conventional husbandry of Institute of Occupational Medicine, Łódź, Poland
- Age at study initiation: females 9 weeks, males 10 weeks
- Weight at study initiation: see Table 2 in the section Any other informartion on results incl. tables
- Fasting period before study: animals were not fasted prior to the experiment
- Housing: The animals were kept in cages with plastic bottom and wired lid of dimensions (length x width x height) 58 x 37 x 21 cm. After application of the test item each animal was kept individually in a cage. After removal of the test item from the skin, during the following days of the experiment, animals were kept five per cage, each sex separately. UV-sterilized wooden shavings were used as the bedding.
- Diet (e.g. ad libitum): ad libitum. The animals were given standard granulated "Murigran" fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz, Poland
- Water (e.g. ad libitum): ad libitum, The animals were given tap water.
- Acclimation period: the animals were quarantined and observed daily for at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 27
- Humidity (%): 40 - 70
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

other: The test item was held in contact with the skin with a porous gauze dressing

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: masel 42 cm2, females 36 cm2
- % coverage: ca. 10
- Type of wrap if used: the gauze patches were covered with PVC foil and elastic bandage was used to make circular protecting band

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test item was removed from the skin using water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: evaluation of general condition of animals was performed twice a day (once a day on days off). Detailed clinical observations were performed at hourly intervals after administration of the test item (day 0). From 1st to 14th day of the observation period detailed clinical observations were performed once a day. bw of animals was individually determined for each animal directly before administration of the test item and then on the 7th and the 14th day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the test.

Clinical signs:

other: Following administration of the test item, no pathological changes were stated on skin of males and females. No other clinical signs were stated during the test in any of the animals - see Table 1 in the section Any other information on results incl. tabl

Gross pathology:

No pathological changes were stated in animals at the necropsy.

Any other information on results incl. tables

Table 1. Acute dermal toxicity study on rats – clinical signs – overall list

Dose mg/kg bw	Sex	Day after administration	No. of alive animals	Rat No.
				1	2	3	4	5
2000	males	0 1 2 3 4 5 6 7 8 9 10 11 12 13 14	5 5 5 5 5 5 5 5 5 5 5 5 5 5 5	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC
	females	0 1 2 3 4 5 6 7 8 9 10 11 12 13 14	5 5 5 5 5 5 5 5 5 5 5 5 5 5 5	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC	NC NC NC NC NC NC NC NC NC NC NC NC NC NC NC

NC – no changes

 

Table 2. Acute dermal toxicity study on rats – body weight of animals (g)

Dose mg/kg bw	Sex	Rat No.	Day			Body weight gain (0→14)
			0	7	14
2000	males	1 2 3 4 5	315 297 282 297 279	325 311 299 305 294	349 343 312 314 309	34 46 30 17 30
	females	1 2 3 4 5	217 213 211 223 211	236 218 222 233 211	249 242 239 251 227	32 29 28 28 16

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

As median dermal acute dose (LD50) for Atlen SK is > 2000 mg/kg it is not classified as dangerous in accordance with both the DSD and the CLP regulation.

Executive summary:

Presented results originate from a guideline study conducted in accordance with the requirements of the GLP. Hence, this information can be considered reliable and suitable for use as the key study for this endpoint.