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

Endpoint summary

Description of key information

LD50 oral for Atlen SK is > 2000 mg/kg bw
LD50 dermal for Atlen SK is > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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)

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

Preliminary study:

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity of Atlen SK was tested in vivo via the oral and the dermal route.

In acute oral toxicity study of Atlen SK no signs of toxicity were stated at the limit dose of 2000 mg/kg bw.

In acute dermal toxicity study of Atlen SK no signs of toxicity were stated at the limit dose of 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
One study available.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

Data available for Atlen SK is conclusive but not sufficient for the classification of Atlen SK with regard to acute toxicity.