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Description of key information

There are no reliable data available for acute oral, inhalative and dermal toxicity of n-octyl methacrylate.


However, methyl- and n-butyl methacrylate, and 2-ethylhexyl methacrylate analogue substances and members of the category C1 -C8 lower alkyl methacrylates are of low toxicity (LD0/rabbit >= 2000 mg/kg) by the dermal route and oral route (LD50/rat: >= 2000 mg/kg). As well, methyl-, ethyl- and n-butyl methacrylate are also of low acute inhalation toxicity with 4-h LC50 in rats of 28.9, 55.0 and 29.0 mg/l, respectively.
Due to the low vapour pressure, inhalation is not considered as a relevant route of exposure for n-octyl methacrylate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
Reliable data are available for all members of the category except n-octyl methacrylate. The more recent studies were conducted to modern guidelines up to the limit dose of 2000 mg/kg.
The substances of the category C1-C8 Lower Alkyl Methacrylates are all of low acute oral toxicity. This was demonstrated in several guideline studies which cover the range of C1 to C8. Please see Chapter 5.2.1.1 Summary of Acute Oral Toxicity Data
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Co. (Hino Breeding Center)
- Age at study initiation:
- Weight at receipt: 113-120g for males and 95-106 for females
- Fasting period before study: yes
- Housing: Stainless steel cage systems (W: 240 x D: 380 x H: 200mm) were used during quarantine and acclimatization, and 5 rats were housed in each cage. After dividing into groups, a rack of five stainless steel cages (W: 755 x D: 210 x H: 170mm) were used for individual housing.
- Diet (ad libitum): CRF-1, Oriental Yeast Co.
- Water (ad libitum): tap water
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 45-53
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0, 50, 100 or 200 mg/ml
- Amount of vehicle (if gavage): 5 ml/kg
- Justification for choice of vehicle: solubility
Doses:
0 (vehicle), 500, 1000, 2000 mg/kg/day
No. of animals per sex per dose:
five
Control animals:
yes
Details on study design:
Post dose observation period: 14 days
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Weighing: Days 1, 3, 7, 10 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths in any group
Clinical signs:
Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle.
Body weight:
A tendency of the depression of body weight gain was observed on the second day in both sexes.
Gross pathology:
No treatment related macroscopic abnormality was observed.
Conclusions:
The LD0 value was more than 2000 mg/kg for males and females.
Executive summary:

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Crj: CD(SD) rats according to OECD N°401 guideline and in compliance with principles of Good Laboratory Practices. Animals were treated by gavage at the dose level of 2000 mg/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. No mortality was recorded in the 14 day-observation period. Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle. A tendency of the depression of body weight gain was observed on the second day in both sexes. No treatment related macroscopic abnormality was observed. Under these experimental conditions, the oral LD0 of 2-ethylhexyl methacrylate is higher than 2000 mg/kg in female/male rats.

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
no data regarding GLP
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
Reliable data are available for all members of the category except n-octyl methacrylate. The more recent studies were conducted to modern guidelines up to the limit dose of 2000 mg/kg.
The substances of the category C1-C8 Lower Alkyl Methacrylates are all of low acute oral toxicity. This was demonstrated in several guideline studies which cover the range of C1 to C8. Please see Chapter 5.2.1.1 Summary of Acute Oral Toxicity Data
Qualifier:
according to
Guideline:
other: Appraisal of the safety of chemicals in foods, drugs and cosmetics", Staff of the Division of Pharmacology, FDA (1959)
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 140-180g
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): Ssniff, Intermast
- Water (e.g. ad libitum): tap water
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45-55
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg
Doses:
10.0, 12.6, 15.9, and 20.0 ml/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations, 10 min, 1, 3, 24 hours, 7 and 14 days after administration
- Weighing: on day 0 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
18.5 mL/kg bw
95% CL:
>= 14.8 - <= 23.13
Remarks on result:
other: 16465 mg/kg bw
Mortality:
Dose 24h 14 days
10 ml/kg 0/10 1/10
12.6 ml/kg 0/10 1/10
15.9 ml/kg 1/10 3/10
20.0 ml/kg 3/10 6/10
Clinical signs:
Reduced activity, impairment of coordination, exophthalmos, piloerection;
Body weight:
At the end of the observation period, the body weight of the animals were in a normal range.
Gross pathology:
Reddening of mucous membranes in the stomach and the intestine.
Interpretation of results:
GHS criteria not met
Conclusions:
In a valid guideline study, the acute oral LD50 in rats was 16465 mg/kg bw.
Executive summary:

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Wistar rats according to FDA (1959) guideline. Animals were treated by gavage at the dose level of 10.0, 12.6, 15.9, and 20.0 ml/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. Mortality was observed in 1/10, 1/10, 3/10 and 6/10 rats in the 14 day-observation period, respectively. Reduced activity, impairment of coordination, exophthalmos and piloerection were observed up to 24 hours after treatment. At the end of the observation period, the body weight of the animals were in a normal range. Reddening of mucous membranes was observed in the stomach and the intestine. Under these experimental conditions, the oral LD50 of 2-ethylhexyl methacrylate was 18.5 ml/kg bw (16465 mg/kg bw).

In a valid guideline study, the acute oral LD50 in rats was 16465 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:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Referring to "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology, FDA, 1959
Justification for type of information:
Read across from the n-hexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
Reliable data are available for all members of the category except n-octyl methacrylate. The more recent studies were conducted to modern guidelines up to the limit dose of 2000 mg/kg.
The substances of the category C1-C8 Lower Alkyl Methacrylates are all of low acute oral toxicity. This was demonstrated in several guideline studies which cover the range of C1 to C8. Please see Chapter 5.2.1.1 Summary of Acute Oral Toxicity Data
Qualifier:
according to
Guideline:
other:
Version / remarks:
"Appraisal of the safety of chemicals in food, drugs and cosmetics", by the staff of the Division of Pharmacology; FDA, 1959
Principles of method if other than guideline:
The test item was applied undiluted via gavage once at test start.
Prior to administration of the test item, the animals were not fed for 16 hours.
The administration was followed by a observation period of 14 days.
Afterwards an necropsy was performed.
The test item is a clear liquid with a pH value of 6.0.

GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Paderborn
- Females (if applicable) nulliparous and non-pregnant: [yes/no] not specified
- Age at study initiation: not specified
- Weight at study initiation: 150 - 230 g
- Fasting period before study: 16 h
- Housing: individual housing
- Diet (e.g. ad libitum): ad libitum; Ssniff/ Intermast
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 45 -55 %
- Air changes (per hr): not applicable
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: no vehicle

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg
Doses:
20 mL/kg = 17,720 mg/kg (density: 0.885 g/cm³)
No. of animals per sex per dose:
10 male
10 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: listed after 1, 2, 5, 7, 14 days; observations : 20 min, 1h, 3h, 24h, 7d, 14d; weighing at test start and termination (14 days)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs; observations : 20 min, 1h, 3h, 24h, 7d, 14d
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 17 720 mg/kg bw
Based on:
test mat.
Remarks on result:
other: original value: LD50: approx. 20 mL/kg bw (8 of 20 animals were dead after 14 days of observation
Mortality:
24h: 0/20
14d: 8/20 (8 days after administration)
Clinical signs:
Reduced activity, disturbed coordination, hyperthermia, diarrhea, piloerection
Body weight:
Test start: avarege weight 197.50 g
Termination: avarege weight 228.18 g
Gross pathology:
Deceased animals had a gastrointestinal flush.
Sacrificed animals showed no macroscopic anomalies.

The LD50 > 20 ml/kg bw equals to 17720 mg/kg bw(density 0.886 g/cm³)

Interpretation of results:
GHS criteria not met
Conclusions:
According to the test result: LD50 (14days / >17720 mg/kg bw): > 5000 mg/kg bw the test substance n-Hexyl methacrylate has to be classified as practically nontoxic in rats in respect of its acute oral toxicity.
Executive summary:

In an acute oral toxicity study ( According to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics", by the Staff of the Division of Pharmacology, FDA, 1959)

groups of ten male and ten female SPF-Wistar rats (weight: 150 to 230 g) were given a single oral dose of 20 ml/kg n-Hexylmethacrylate. Animals were then observed for 14 days.

Oral LD50 Combined: > 20 mL/kg (equals to  >17720 mg/kg (density 0.886 g/cm3))

8 of 20 animals died within the first 8 days after administration of the test item. These animals showed a gastrointestinal flush. The sacrificed animals instead showed no macroscopic anomalies. The average bodyweight rose from 197.50 g to 228.18 g per animal.

n-Hexyl methacrylate led to a reduced activity, disturbed coordination, hyperthermia, diarrhea and piloerection 20 minutes after the administration. These symptoms were vanished after 24 hours and the surviving animals showed a normal behavior.

n-Hexyl methacrylate is of very low oral toxicity based on this LD50test in males and females.

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:
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:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Data from secondary source (peer-reviewed handbook). The data are reported to be unpublished, original data of the author (Fasset) from the Laboratory of Industrial Medicine, Eastman Kodak Co., Rochester NY Insufficient information to determine reliability
Justification for type of information:
Read across from the 2 Ethylhexyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
PM_Lower Alkyl (C1-C8) Methacrylates
This is a category (C1-C8 Lower Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
There are only limited acute dermal toxicity data for the members of the category C1-C8 Lower Alkyl Methacrylates available. Guideline studies are only available for MMA and nBMA. There are reliable data for MMA and nBMA indicating that these esters are of low acute dermal toxicity. There are also two early pre-guideline studies of limited reliability available in guinea pigs for i-BMA and 2-EHMA that indicate low acute dermal toxicity and although there is no fully valid study for 2-EHMA, the upper bound of the category, there is a trend of decreasing skin absorption across the category (see section 5.1) indicating that the acute dermal toxicity of all members will be equally low. This is supported by the observation that the members are all of low acute oral toxicity.
Qualifier:
according to
Guideline:
other: not known
Principles of method if other than guideline:
other
GLP compliance:
no
Test type:
standard acute method
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Remarks on result:
other: 17620 mg/kg bw
Conclusions:
A published LD50 >20 ml/kg bw in guinea pigs is available.
Executive summary:

A published LD50 >20 ml/kg bw in guinea pigs is available.

Additional information

There are no reliable data available for acute oral, inhalative and dermal toxicity of n-octyl methacrylate.

Reliable data of acute oral route are available for all members of the category C1-C8 Lower Alkyl Methacrylate except n-octyl methacrylate. The most recent studies were conducted to modern guidelines up to the limit dose of 2000 mg/kg.

The substances of the category C1-C8 Lower Alkyl Methacrylates are all of low acute oral toxicity. This was demonstrated in several guideline studies which cover the range of C1 to C8.

Read across to 2 -EHMA also member of the category:

Oral route

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Crj: CD(SD) rats according to OECD N°401 guideline and in compliance with principles of Good Laboratory Practices (Furuhashi et al., 1998). Animals were treated by gavage at the dose level of 2000 mg/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. No mortality was recorded in the 14 day-observation period. Although soft faeces were observed in all treated groups, these effects were considered to be attributable to corn oil used as a vehicle. A tendency of the depression of body weight gain was observed on the second day in both sexes. No treatment related macroscopic abnormality was observed. Under these experimental conditions, the oral LD0 of 2-ethylhexyl methacrylate is higher than 2000 mg/kg in female/male rats.

The Acute oral toxicity of 2-ethylhexyl methacrylate was evaluated in male and female Wistar rats according to FDA (1959) guideline (Sterner, 1977). Animals were treated by gavage at the dose level of 10.0, 12.6, 15.9, and 20.0 ml/kg and then observed for 14 days for mortality, clinical signs and effect on body weight. Mortality was observed in 1/10, 1/10, 3/10 and 6/10 rats in the 14 day-observation period, respectively. Reduced activity, impairment of coordination, exophthalmos and piloerection were observed up to 24 hours after treatment. At the end of the observation period, the body weight of the animals was in a normal range. Reddening of mucous membranes was observed in the stomach and the intestine. Under these experimental conditions, the oral LD50 of 2-ethylhexyl methacrylate was 18.5 ml/kg bw (16465 mg/kg bw).

Inhalation route

No reliable data are available on 2-ethylhexyl methacrylate for the inhalation route. However, data are available on analogue substances: methyl-, ethyl- and n-butyl methacrylate. The respective LC50 values are in a range between 5000 and 11000 ppm indicating low inhalation toxicity.

At ambient temperature 2-EHMA has a saturated vapour density of 50-100 ppm (64 ppm at 20 °C) and, therefore, it is extremely unlikely that acutely toxic concentrations could ever be reached. Hence, the inhalation pathway is not considered a relevant route of exposure for 2-EHMA.

Dermal route

No reliable data are available on 2-ethylhexyl methacrylate for the dermal route. However, data are available on analogue substances: methyl- and n-butyl methacrylate.

There is one valid study available reporting a LD50 value in rabbits comparable to OECD guideline 402 (Rohm & Haas 1982). Unchanged methyl methacrylate was applied to the clipped skin of two New Zealand White rabbits per dose for 24 h under occlusive conditions. Even under these harsh conditions, no mortality, clinical signs or pathological findings were observed and the LD50 was therefore assessed to be >5000 mg/kg bw. Irritation effects were irreversible within 24 d if 2000 mg/kg bw or more were applied; effects were reversible after application of 200 mg/kg bw within 3 days.

In an OECD 402 and GLP study, a single dose of n-butyl methacrylate was applied to the shaved, intact skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight (Sarver, 1993). The application site was occluded for 24 hours. The rabbits were observed for 14 days following application. No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy. Under the conditions of this test, the acute dermal LD0 for n-butyl methacrylate was greater than 2000 mg/kg of body weight.

Although no fully valid study is available for 2-EHMA, there is an early pre-guideline study available in guinea pigs that indicates low acute toxicity by the dermal route and data on the other two esters of the category (MMA and n-BMA) show low dermal toxicity. 

Furthermore, a skin absorption study indicates that less than 10 % of the applied dose are absorbed through the skin within 30 h and, hence, bearing in mind the already low acute oral toxicity, toxic effects via the dermal route are unlikely. There is a trend of decreasing skin absorption with increasing chain-length of the alkyl moiety of the methacrylate esters indicating that the acute dermal toxicity will be equally low (cf section toxicokinetics). This is supported by the observation that the members are all of low acute oral toxicity and a survey of chemical registrations in the EU demonstrated that acute dermal toxicity was rarely greater than acute oral toxicity (Creton et al. 2010).

Taken as a whole there are sufficient data available for 2 -EHMA for assessment purposes so for the sake of animal welfare it is not proposed to repeat this study.

Justification for classification or non-classification

According to the available data and CLP criteria no classification is warranted for the acute oral, dermal and inhalation toxicity.