2-Propenoic acid, 2-methyl-, C11-14-isoalkyl esters, C13-rich

Endpoint summary

Description of key information

Acute oral toxicity: LD50 (rat, male/female) > 5000 mg/kg bw (OECD TG 401; GLP, RL1)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

BOR:WISW (SPF TNO)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann GmbH & Co KG (D-4799 Borchen)
- Age at study initiation: 9 weeks
- Weight at study initiation: males 215.3 g (mean), females 162.1 g (mean)
- Fasting period before study: yes, overnight
- Housing: groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 d

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL7kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical examination twice a day, bodyweights at start and termination of teh test
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights (lung , livers, kidneys, spleens, adrenals and testes)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Mortality:

Mortality was neither observed in the experimental group nor in the controls during the observation period of 14 days.

Clinical signs:

The clinical appearance and behavior of the male and fema.le rats did not differ from the controls for the wIlole experimental period. The day of and after administration the faeces of the experimental rats were covered by a
oily film, but were of normal viscocity.

Body weight:

Body weight gain in the experimental group was comparable to the control animals.

Gross pathology:

At necropsy no substance-related signs of toxicity were found in comparison to the controls. The only observation was a similar incidence of white foci on the lung surface of the experimental and control rats.

Other findings:

It was found that except of significantly higher mean testes (p < 0.01) and adrenal (p < 0.05) weights in the male rats the experimental results did not differ from those of the controls. These differences were rather small and do not demonstrate a toxic effect of the test substance.

Tissue weight (g) of male and female rats after oral treatment with the test item

	Male rats		Female rats
	Controls	Experimental	Controls	Experimental
Lung	1.12 ± 0.09	1.07 ± 0.09	0.87 ± 0.07	0.89 ± 0.08
Liver	10.37 ± 1.65	10.15 ± 1.08	6.16 ± 0.64	6.55 ± 0.44
Kidneys	1. 76 ± 0.28	1.71 ± 0.17	1.15 ± 0.07	1.18 ± 0.06
Adrenals	0.043 ± 0.004	0.047 ± 0.006*	0.06 ± 0.01	0.06 ± 0.01
Spleen	0.57 ± 0.12	0.60 ± 0.12	0.38 ± 0.04	0.42 ± 0.07
Testes	3.19 ± 0.05	2.94 + 0.14**

 

* p <0.05

** P <0.01

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Isotridecyl methacrylate was >5000 mg/kg bw in rat.

Executive summary:

In an acute oral toxicity study according to OECD Guideline 401, groups of fasted, 9 weeks old Wistar rats (5/sex) were given a single oral dose of Isotridecyl methacrylate at a limit dose of 5000 mg/kg bw and observed for 14 days. Untreated control animals were included. During an observation period of 14 days there was neither lethality nor toxicity in relation to the treatment of the substance. 

Oral LD50 combined >5000 mg/kg bw

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 202 - 226 g (males), 208 - 223 g (females)
- Fasting period before study: yes, overnight + 3 to 4 h after dosing
- Housing: in groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21°C
- Humidity (%): 44 - 53%
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
2.3 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1 (range finding study)
5 (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (main study), 5 (dose range finding study)
- Frequency of observations and weighing: observations 1, 2 and 4 hours after dosing and subsequently once daily; individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Preliminary study:

There were no deaths or clinical signs of toxicity. Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

All animals showed an expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of Isotridecyl methacrylate was > 2000 mg/kg bw in rat.

Executive summary:

In an acute oral toxicity study according to OECD Guideline 401, fasted, 8-12 weeks old Sprague-Dawley rats (5/sex) were given a single oral dose of Isotridecyl methacrylate at a limit dose of 2000 mg/kg bw and observed for 14 days.

There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

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

Additional information

Reliable, relevant and adequate data are available for the acute oral toxicity of Isotridecyl methacrylate.

 

Acute oral toxicity

In an acute oral toxicity study according to OECD Guideline 401, groups of fasted, 9 weeks old Wistar rats (5/sex) were given a single oral dose of Isotridecyl methacrylate at a limit dose of 5000 mg/kg bw and observed for 14 days. Untreated control animals were included. During an observation period of 14 days there was neither lethality nor toxicity in relation to the treatment of the substance. 

Oral LD50 combined >5000 mg/kg bw

 

In an acute oral toxicity study according to OECD Guideline 401, fasted, 8-12 weeks old Sprague-Dawley rats (5/sex) were given a single oral dose of Isotridecyl methacrylate at a limit dose of 2000 mg/kg bw and observed for 14 days.

There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.

 

The source substances Dodecylmethacrylate and 2 -Ethylhexyl methacrylate, which are used as read-across substance for the endpoint repeated dose toxicity and toxicity to reproduction, were of comparably low toxicity after single administration.

In an acute oral toxicity study according to OECD guideline 401 (Limit test), groups of fasted male and female SPF Wistar rats were given a single oral dose of Dodecylmethacrylate (purity: 97%) at a dose of 5000 mg/kg bw and observed for 14 days. Oral LD50 Combined = > 5000 mg/kg bw

The oral LD50 of 2 -Ethylhexyl methacrylate is reported to be >2000 mg/kg bw.

 

Acute inhalation toxicity

A study on acute inhalation toxicity is unjustified in accordance to REACH regulation Annex XI due to scientific considerations. Results of laboratory animal studies show a low acute toxicity after oral exposure. Therefore, the acute intrinsic toxic activity of Isotridecyl methacrylate is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified. Thus, also animal welfare is respected according to REACH intentions.

 

Acute dermal toxicity

The testing of acute dermal toxicity of Isotridecyl methacrylate is scientifically not justified. According to the COMMISSION REGULATION (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity, recent “scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.” The oral LD50 was determined to be > 5000 mg/kg bw. Thus, no toxicity via the dermal route is to be expected.  

 

There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

Based on the available data, Isotridecyl methacrylate does not need to be classified for acute toxicity according to regulation (EC) 1272/2008. Thus, no labelling is required.