Reaction mass of dodecyl methacrylate and tridecyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 (rat, female) > 5000 mg/kg bw (OECD TG 423; 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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Groups of two male and two female Alderley Park SPF albino rats were used, bodyweight range 240-253g for males and 181-203g for females. The animals were fasted for a period of up to 24 hours immediately prior to dosing.
Preparations of the test sample, in corn oil, were then dosed at a standard volume of 10 mL/kg. On Day 1 single doses of 25, 200 and 2000 mg/kg were administered by stomach tube to separate groups of animals. The animals were observed daily up to Day 8 and then on Day 15. At the end of the study the animals were humanely killed by inhalation of excessive levels of halothane BP and were examined by necropsy for any macroscopic abnormalities. The acute oral median lethal dose was estimated from the mortality data.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Alderley Park SPF albino rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 240-253 g (males), 181-203 g (females)
- Fasting period before study: 24 hours immediately prior to dosing

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

25, 200 and 2000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: dai1y up to Day 8 and then on Day 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the animals died.

Clinical signs:

other: There were no significant signs of toxicity after a single oral dose of 25, 200 or 2000 mg/kg bw.

Gross pathology:

No macroscopic abnorma1ities were detected at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Reaction mass of dodecyl methacrylate and tridecyl methacrylate to rat was >2000  mg/kg bw .

Executive summary:

In an acute oral toxicity study, groups of fasted, young adult Alderley Park SPF albino rats 2/sex/dose were given a single oral dose of  Reaction mass of dodecyl methacrylate and tridecyl methacrylate in corn oil at doses of  25, 200 and 2000 mg/kg bw and observed for 15 days.

None of the animals died and there were no significant signs of toxicity.

Oral LD50 Males/Females >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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 January 2018 to 8 March 2018 (Study Initiation to experimental completion)

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

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:

SOURCE OF TEST MATERIAL
- Source of test material: Kyoeisha Chemical Co. Ltd.,
- Lot/batch No.of test material: 7061301
- Expiration date of the lot/batch: June 13, 2019
- Purity test date: 3 October 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (Ambient). Containers kept tightly closed and away from heat or sunlight.
- Stability under test conditions: Assumed stable for the duration of the study
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: None

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, test item was a liquid and was tested undiluted.

Species:

rat

Strain:

Wistar

Remarks:

RccHan : WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks,
- Weight at study initiation: Minimum: 179.8g, Maximum: 208.6g
- Fasting period before study: Overnight fasting prior to dosing and three hours post-dose
- Housing: Polypropylene rat cages covered with a stainless steel grid top. Autoclaved clean rice husk was used as bedding material. Wooden chew blocks were provided as enrichment material.
- Diet (e.g. ad libitum): Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA.
- Water (e.g. ad libitum): UV sterilized water filtered through a Reverse Osmosis water filtration system.
- Acclimation period: 6 to 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 57 to 67%
- Air changes (per hr): Minimum 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h (photoperiod was maintained through an automatic timer)

IN-LIFE DATES: From: To: 1 February 2018 to 8 March 2018 (Experimental start to experimental completion)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

The test item was tested undiluted (at a constant concentration).

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: The individual dose volume was adjusted according to body weight and dose level but will not normally exceed 10 mL/kg body weight. All rats were dosed by oral gavage (day 0) using a BD 1 mL disposable syringe.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Three animals were used for each step, starting at a dose of 300 mg/kg body weight as no toxicological information is available for the test item.

Doses:

In accordence with OECD 423, Annex 2c:
300 mg C12-13 alkyl methacrylate/kg bw and 2000 mg C12-13 alkyl methacrylate/kg bw

No. of animals per sex per dose:

6 female rats (nulliparous and non-pregnant) per dose level

Two groups of 3 female rats at 300 mg C12-13 alkyl methacrylate/kg bw
Two groups of 3 female rats at 2000 mg C12-13 alkyl methacrylate/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. Clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes. At the end of 14 day observation period, all rats were euthanised by carbon dioxide asphyxiation and were subjected to gross pathological examination, consisting of external examination and opening of the abdominal and thoracic cavities.
- Other examinations performed: Clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 0 and on days 7 and 14.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in rats treated with 300 or 2000 mg C12-13 alkyl methacrylate/kg bw.

Clinical signs:

other: No clinical signs were observed in all rats treated with 300 or 2000 mg C12-13 alkyl methacrylate/kg bw.

Gross pathology:

Necropsy (Macroscopic Findings):
External examination of terminally sacrificed rats did not reveal any abnormality.
Internal: Visceral examination of terminally sacrificed rats did not reveal any abnormality.

In absence of any pathological lesion in terminally sacrificed rats, it is concluded that the test item did not produce any treatment related effect at the dose levels used in the present study.

Dose (mg/kg body weight)	Female rats (mortality/total)
300	0/6
2000	0/6

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50 cut- off value) C12-13 alkyl methacrylate in Wistar rats was found to be 5000 mg/kg body weight.
Based on the results of this study, the classification for C12-13 alkyl methacrylate is as follows:

Globally Harmonized System of Classification and
Labelling of Chemicals (GHS 2017) : Category 5 or Unclassified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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

Additional information

Reliable, relevant and adequate data are available for the acute oral toxicity of Reaction mass of dodecyl methacrylate and tridecyl methacrylate.

 

Acute oral toxicity

The acute oral median lethal dose (LD50 cut-off value) of Reaction mass of dodecyl methacrylate and tridecyl methacrylate in Wistar rats was determined to be 5000 mg/kg body weight.

In an acute oral toxicity study, groups of fasted, young adult Alderley Park SPF albino rats 2/sex/dose were given a single oral dose of  Reaction mass of dodecyl methacrylate and tridecyl methacrylate in corn oil at doses of 25, 200 and 2000 mg/kg bw and observed for 15 days.

None of the animals died and there were no significant signs of toxicity.

Oral LD50 Males/Females >2000 mg/kg bw

 

The source substance Dodecyl methacrylate, which is used as read-across substance for the endpoint repeated dose toxicity and toxicity to reproduction, was 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 Dodecyl methacrylate (purity: 97%) at a dose of 5000 mg/kg bw and observed for 14 days. Oral LD50 Combined = > 5000 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 Tridecyl 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 Reaction mass of dodecyl methacrylate and tridecyl 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 > 2000 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.

 

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

Justification for classification or non-classification

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