6-{4-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenoxy}hexyl methacrylate

Endpoint summary

Description of key information

The LD50 of the test item ROC-601 is higher than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure of OECD Guideline 423 with a Starting Dose of 2000 mg/kg body weight, and recognizing no mortality or adverse effects in any of the animals used at that dose (0/6 moribund or dead animals), it can be concluded that the test item ROC-601 is unclassified according to GHS with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

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

Study period:

November - December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Test Item ROC-601
Lot Number S23PSG0816
CAS No 439661-46-8
Purity 99.5% by LC-UV
Appearance White crystalline powder
Composition 99.5%
Homogeneity Uniform crystalline powder
Production Date 29 June 2016
Expiry Date July 2017
Storage Room Temperature (20 ± 5 °C), keep away from light

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species: Wistar rats
Source: Dobrá Voda, Slovak Republic
Number and Sex of Animals: 6 females
Age at First Dose: 8 - 12 weeks; female animals were non-pregnant and nulliparous
Animal Health: The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22.1 ± 0.3 °C, relative humidity within 56.3 ± 2.5 %. The light regime was set to a 12-hour light /12-hour dark cycle. The sanitation was performed according to the standard operation procedures.
Diet: A laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered in recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.
Water: The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodically analysed (including microbiological control) and recorded; a certificate of analysis is included in raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line on the tail with an ink marker.

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighted, and the test item was administered. After the test item had been administered, food was withheld for a further 3 - 4 hours.

Doses:

According to OECD TG 423 the starting dose is to be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. Available information indicated that the test item is likely to be non-toxic with regard to acute toxicity. Therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was not observed during 24 hours and therefore in a second step another 3 females were treated at the same dose. The required amount of the test item (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration.

No. of animals per sex per dose:

3 females in initial test and 3 females in verification test, in total 6 females

Control animals:

no

Details on study design:

Observation: The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days.
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body Weights: Individual weights of animals were determined shortly before the test item was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
Necropsy: All test animals were subjected to gross necropsy and result were recorded for each animal.

Statistics:

None applied in lack of effects

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

No mortality was observed during the study.

Mortality:

No mortality was observed during the study. Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.

Clinical signs:

No clinical signs were obersed in any of the 6 female rats investigated

Body weight:

The body weights of 5/6 animals increased during the study. Stagnation of the body weight in 3 animals and mild increase of the body weight in the rest animals was observed between first and second week after administration.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were noticed.

Other findings:

None

Clinical Observations overview:

Observation	Time After Administration
	Hour					Day
	Immediately	0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Skin and Hair	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Eyes	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Mucosa	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Respiratory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Circulatory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
CNS	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Somatomotoric Activity	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Tremor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Spasms	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Salivation	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Diarrhoea	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Lethargy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Sleep	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Coma	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Death	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

- mean "No observed signs"

Body weights

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	200	200	200	0	0	0
		2	200	210	215	10	15	5
		3	180	195	210	15	30	15
		4	175	195	195	20	20	0
		5	185	200	200	15	15	0
		6	165	190	195	25	30	5

Necropsy results:

Sex	Dose	ID	Result	Sex	Dose	ID	Result
♀	2000 mg/kg	1	no finding	♀	2000 mg/kg	4	no finding
		2	no finding			5	no finding
		3	no finding			6	no finding

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item ROC-601 is higher than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure of OECD Guideline 423 with a Starting Dose of 2000 mg/kg body weight, and recognizing no mortality or adverse effects in any of the animals used at that dose (0/6 moribund or dead animals), it can be concluded that the test item ROC-601 is unclassified according to GHS with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The test item ROC-601 administered to 6 females at limit dose of 2000 mg/kg body weight did not cause death. Stagnation of the body weight in 3 animals and mild increase of the body weight in the rest animals was observed between first and second week after administration. No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours in females or 14 -day observation period. During necropsy, no macroscopic findings were noticed.

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

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The LD50 of the test item ROC-601 is higher than 2000 mg/kg body weight after single oral administration to Wistar rats. Based on Annex 2d Test Procedure of OECD Guideline 423 with a Starting Dose of 2000 mg/kg body weight, and recognizing no mortality or adverse effects in any of the animals used at that dose (0/6 moribund or dead animals), it can be concluded that the test item ROC-601 is unclassified according to GHS with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats. Likewise, according to CLP (Regulation EC No 1272/2008) the substance is not subject to classification for acute oral toxicity and also not for STOT single exposure. Aspiration hazards is not applicable as the substance is not a hydrocarbon and not liquid at ambient temperature.