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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

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.: probka of 12-12-2008
- Expiration date of the lot/batch: 2009-12-13
- Stability under test conditions: stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

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: 10 weeks
- Weight at study initiation: see Table 2 in section Any other information on results incl. tables
- Fasting period before study: the day before the start of the experiment (about 19 hrs before administration of the test item) the food was withheld. Water was still available. The food was restored 3 hours after administration of the test item.
- 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. The animals were kept in the cages individually (the sighting study) or four rats per cage (the main study). UV sterilized wooden shaving were used as the bedding.
- Diet (e.g. ad libitum): ad libitum. The animals were given standard granulated "Murigran" foodstuff 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: prior to the start of the dosing the animals were quarantined and observed daily for at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 37 - 60
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12 (artificial light)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg/ml
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: corn oil is typically used in oral acute toxicity studies and it is compatibile with Atlen SK

MAXIMUM DOSE VOLUME APPLIED: 0.5 ml per 100 g of bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: evaluation of general condition of animals was conducted twice a day (once on days off). detailed clinical observations were performed at the day of administration after 10, 30 and 60 minutes since administration and then in hourly intervals - till the 5th hour after administration. From 1st to 14th day of the observation period clinical observations were performed once a day. bw of animals was individually determined directly before administration of the test item (day 0) and then on 7th and 14th day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Preliminary study:

The sighting study performed on a single animal at the dose of 2000 mg/kg bw revealed no signs of toxicity.

Effect levels

Sex:

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: No clinical signs were stated during the test in any of the animals - see Table 1 in the section Any other information on results incl. tables.

Gross pathology:

No pathological changes in any of the animals were stated at the necropsy.

Any other information on results incl. tables

Table 1. Atlen SK Acute oral toxicity on rats – clinical signs – overall list

Dose (mg/kg b.w.)	Day after administration	Number of alive animals	Rat No.
			1*	2	3	4	5
2000	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

* female from the sighting study

NC = no changes

 

 

Table 2. Atlen SK Acute oral toxicity on rats – body weight of animals (g)

Dose (mg/kg b.w.)	Rat No.	Day of experiment			Body weight gain (0 →14)
		0	7	14
2000	1* 2 3 4 5	196 210 208 209 214	210 238 237 234 230	235 248 254 230 246	39 38 46 21 32

* female from the sighting study

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

As median oral 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.