Docosyl methacrylate

Endpoint summary

Description of key information

The acute toxicity of Docosyl methacrylate is very low (LD50 > 2000 mg/kg bw). The acute toxicity of the structural analogue substance Isodecyl methacrylate by the dermal route (LD50: > 3000 mg/kg bw) is very low as well. The inhalation route is not of relevance due to the very low vapour pressure estimated for solid waxen Docosyl methacrylate.

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:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, German
- Age at study initiation: young adult females (approx. 10 weeks)
- Weight at study initiation: 160 - 250 g (+/- 20% of the mean weight)
- Housing: single
- Fasting period before study: at least 16 hours before administration
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany (ad libitum)
- Water (e.g. ad libitum): tap water (ad libitum)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: In all animals of the first and second test group impaired general state and piloerection were observed from hour 4 until hour 5 after administration.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of Docosyl methacrylate after oral admininstration was found to be greater than 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

OECD 423

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Due to the very low vapour pressure, which is estimated as 1.96E-5 Pa at 25°C for Docosyl methacrylate, it is extremely unlikely that inhalation toxic concentrations could ever be reached. Hence, the inhalation pathway is not considered a relevant route of exposure for long-chain methacrylate esters (C12 – C22) including Docosyl methacrylate as solid waxen substance

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation of the study

Guideline:

other: OSHA Toxicity Screening Test

GLP compliance:

no

Remarks:

pre-GLP

Test type:

other: single dose

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Doses:

3000 mg/kg

No. of animals per sex per dose:

6

Key result

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

In the observation period of 14 days, 2 of 6 experimental animals died.

Clinical signs:

other: As signs of intoxiciation, only hypoactivity was reported.

Interpretation of results:

GHS criteria not met

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OSHA Toxicity Screening Test. Limited documentation of the study. No detailed description of the test substance available.

Guideline:

other: OSHA Toxicity Screening Test

GLP compliance:

no

Remarks:

pre-GLP

Test type:

other: single dose

Limit test:

yes

Species:

rabbit

Strain:

other: albino rabbits

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Doses:

Dosage: 5000 mg/kg

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 7 and 14 days
- Other examinations performed: clinical signs, body weight

Key result

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

In the observation period of 14 days, 1 of 6 experimental animals died.

Clinical signs:

other: Dodecyl pentadecyl methacrylate was severely irritating to the skin of the albino rabbit. Skin changes at 24 hours were characterized by pale red to red, well-defined erythema, moderate edema and second degree burns. Escharosis, wrinkling and fissuring we

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Quality of whole database:

OSHA toxicity screening test (Read-Across)

Additional information

Oral

In an acute oral toxicity study performed according to the Acute Toxic Class Method, 2000 mg/kg bw of the undiluted test item Docosyl methacrylate were administrated by gavage to test group of three fasted Wistar rats. No mortality occurred. The acute oral LD50 was calculated to be > 2000 mg/kg bw (BASF SE, 2018).

In an acute oral toxicity study according to OECD TG 401, groups of fasted Sprague Dawley rats (5 males + 5 females) were given a single oral dose of Dodecyl methacrylate (5000 mg/kg bw) and observed for 14 days. No death occurred. The body weight gain of the treated animals was similar to that of control animals. At necropsy substance-related signs of toxicity were not clearly obvious in comparison to the controls. The only observations were similar incidences of red and white foci on the lung surface of the experimental and control rats. But in 2/5 male and 1/5 female rats slightly swollen liver margins were observed for the experimental group only. The LD50 (rat) was  > 5000 mg/kg bw (Evonik Röhm GmbH UNTER 88-021).

In a further acute oral toxicity study, groups of fasted male and female SPF Wistar rats received a single oral dose of 2-Propenoic acid, 2-methyl-, C12-16-alkyl esters at a dose of 20.0 mL/kg bw and observed for 14 days. The LD50 was reported to be > 20.0 mL/kg bw (equals > 17500 mg/kg bw) (Evonik RohMax Additives GmbH UNTER77-004).

In a supporting acute oral toxicity study according to OECD TG 401 (limit test), groups of fasted male and female SPF Wistar rats were given a single oral dose of Isotridecyl methacrylate (5000 mg/kg bw) and observed for 14 days. The LD50 was > 5000 mg/kg bw for males and females (Evonik Röhm GmbH UNTER 89-009).

Inhalation

There is no acute inhalation study available on Docosyl methacrylate. Due to the very low vapour pressure, which is estimated as 1.96E-5 Pa at 25°C for Docosyl methacrylate, it is extremely unlikely that inhalation toxic concentrations could ever be reached. Hence, the inhalation pathway is not considered a relevant route of exposure for long-chain methacrylate esters (C12 – C22) including Docosyl methacrylate as solid waxen substance.

Dermal

There is no acute dermal toxicity study available on Docosyl methacrylate. However, the acute dermal LD50 of the closely related read-across substance Isodecyl methacrylate is reported to be >3000 mg/kg bw in rabbits (Evonik RohMax GmbH UNTER 00-113). This is supported by a dermal toxicity study with structural analogue Dodecyl methacrylate ,where a LD50 > 5000 mg/kg bw, dermal, rabbit was observed (Rohm & Haas Company UNTER 00-095).

There are only few data on dermal toxicity testing of the long chain alkyl methacrylate esters in rabbits which are of limited reliability. With regard to the low acute oral toxicity and the characteristics of skin penetration and metabolism in the skin, the acute dermal toxicity can be considered as low.

This skin absorption study indicates that the total amount of the ester dodecyl methacrylate that was absorbed during the time of exposure was 0.7 % (rat epidermis) and 0.26 % (rat whole skin) over 24 hours, respectively. Hence, bearing in mind the already low acute oral toxicity, toxic effects via the dermal route are unlikely.

In conclusion, there are sufficient data available for the toxicological assessment of the long-chain alkyl methacrylate esters. Hence, for the sake of animal welfare it is not proposed to conduct further studies. Based on the available information with structural analogue long-chain alkyl methacrylate esters (C12 -C22), the acute toxicity of Docosyl methacrylate is low for oral and dermal routes of administration in rat and rabbits. Even though there is no information on acute inhalative toxicity, there are no indications that the acute toxicity is higher for this route of exposure.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes. As a result the substance is not considered to be classified for acute oral, dermal or inhalatory toxicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No. 2017/776.