Registration Dossier

Administrative data

Description of key information

Oral:


acute toxicity, oral, rat, OECD 401, LD50 > 2000 mg/kg bw (Cray Valley, Huntingdon, 1998)


acute toxicity, oral, rat, similar OECD 401, LD50 > 2000 mg/kg bw (BASF, 1991).


acute toxicity, oral, rat, similar OECD 401, LD50 > 5000 mg/kg bw (Cognis, Food and Drug research laboratories, 1985).


acute toxicity, oral, rat, protocol not specified, LD50 > 500 mg/kg bw but ≤ 5000 mg/kg bw, note: 2000 mg/kg was not assessed (Cytec, Bio/Dynamics, 1984).


 


Dermal:


acute toxicity, dermal, rabbit, protocol not specified, LD50 > >13200 mg/kg bw (Cytec, Bio/Dynamics, 1984)


 


Inhalation:


No information on acute inhalation available for TMPeoTA.

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:
21 July 1998 to 9 September 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 401 with minor deviation: the certificate of analysis and purity of the test substance are missing.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No certificate of analysis
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
No certificate of analysis
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
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: Harlan U.K. Ltd, Oxon, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 85-97 g
- Fasting period before study: overnight before dosing and for 4 h after dosing
- Housing: in groups of 5 of the same sex
- Diet (e.g. ad libitum): Special Diet Services RMI(E) SQC expanded pellet, ad libitum (except in fasting period)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 July 1998 To: 9 September 1998
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.944 mL/kg bw
Doses:
Preliminary experiment: 3200 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
Preliminary experiment: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: at least twice daily for mortality. At frequent intervals for clinical signs the day after dosing and twice daily thereafter. Body weights were recorded on day 1 (just before dosing) and day 8 for the preliminary experiment and on days 1, 8 and 15 for the main study.
- Necropsy of survivors performed: yes (macroscopic examination)
Statistics:
None
Preliminary study:
At 3200 mg/kg bw, the male rat died within 22 h of dosing. Clinical signs prior to death and in the surviving rat comprised piloerection, hunched posture, walking on toes, abnormal faeces, ungroomed appearance and increased salivation in both animals. In addition, pallid extremities was seen in the female only. There were no other signs of reaction and, with the exception of piloerection, recovery was complete in the female by Day 7. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. No macroscopic abnormalities were noted in the remaining animal at the terminal necropsy on Day 8.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths
Clinical signs:
Piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen.
Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.
Other findings:
No data

Table 1: Individual and group mean bodyweights (g)

Phase of

study

Dose

(mg/kg)

Animal No.

& Sex

Bodyweight (g) at

Day 1

Day 8

Day 15

Death

Preliminary

3200

1 M

96

-

-

84

2 F

99

140

-

-

Main

2000

11M

87

142

197

-

12 M

93

143

188

-

13 M

91

146

193

-

14 M

92

146

194

-

15 M

85

135

175

-

Mean

90

142

189

-

16 F

97

146

171

-

17 F

96

147

176

-

18 F

90

126

151

-

19 F

89

132

158

-

20 F

93

136

165

-

Mean

93

137

164

-

Interpretation of results:
other: Not classified
Conclusions:
The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/CEE and the CLP Regulation (1272/2008).
Executive summary:

In an acute oral toxicity study performed in accordance with GLP and OECD guideline 401, groups of Sprague Dawley rats (5/sex) were given a single oral dose of TMPeoTA undiluted at 2000 mg/kg bw. In a preliminary study, one male and one female received a single oral dose of TMPeoTA undiluted at 3200 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 8 days in the preliminary experiment and for 15 days in the main study. They were all macroscopically necropsied after death or sacrifice.

In the preliminary experiment, the male rat died within 22 h of dosing. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. Such effects were not observed in the female rat. In the main study, piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen. Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10.

The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
There are a few studies available assessing the acute oral toxicity. All studies result point to the same result, but only one study is conducted according to OECD guideline under GLP (Cray Valley, Huntingdon, 1998, McRae L.A.). As this study is also the latest conducted and very well documented study this study is assigned as key study.

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:
experimental study
Adequacy of study:
key study
Study period:
From February 13, 1984 to April 11, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
An acute dermal toxicity study was performed in rabbits. The test material was administered at a single dose level and observations were made for a period of 7d.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
IN-LIFE DATES: From: 1984-02-13 to: 1984-08-03
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 12000 mL/kg bw
Duration of exposure:
No data
Doses:
13200 mg/kg bw
No. of animals per sex per dose:
Four
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 d
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 13 200 mg/kg bw
Mortality:
None
Clinical signs:
Lack of food consumption was reported in one animal on days 5 and 6.
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
not classified
Conclusions:
The acute dermal LD50 of ethoxylated trimethylolpropane triacrylate (TMPeoTA) was determined to be >13,200 mg/kg bw in rabbits.

Executive summary:

A study was conducted to evaluate the acute dermal toxicity of ethoxylated trimethylolpropane triacrylate (TMPeoTA) in albino rabbits. A dermal application of 13,200 mg/kg TMPeoTA was applied to 4 rabbits. Parameters evaluated included mortality, clinical observations and body weight for a period of 7 days. No mortality was observed. Lack of food consumption was reported in one animal on days 5 and 6. In conclusion, the single dermal median lethal dose (LD50) of TMPeoTA was determined to be >13,200 mg/kg bw in rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
13 200 mg/kg bw
Quality of whole database:
One key study available (Klimisch scoe 2).

Additional information

Oral:


OECD conform studies:


In an acute oral toxicity study performed in accordance with GLP and OECD guideline 401(Cray Valley, Huntingdon, 1998), groups of Sprague Dawley rats (5/sex) were given a single oral dose of TMPeoTA undiluted at 2000 mg/kg bw. In a preliminary study, one male and one female received a single oral dose of TMPeoTA undiluted at 3200 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 8 days in the preliminary experiment and for 15 days in the main study. They were all macroscopically necropsied after death or sacrifice. In the preliminary experiment, the male rat died within 22 h of dosing. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. Such effects were not observed in the female rat. In the main study, piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen. Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10. The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats.


 


Studies according to other protocols:


A limit test similar to OECD 401 was conducted to assess the acute oral toxicity of the test substance (BASF, 1991). Therefore, 10 (5 female and 5 male) Wistar rats received a single oral of 2000 mg/kg bw TMPeoTA solved in olive oil via gavage. No moralities were observed during the following 14 day observation period. No other unusual findings were reported. The pathologic examination after the end of the experiment reveals nothing unusual. The LD50 was determined as > 2000mg/kg bw.


The above referenced test article was evaluated in another test for acute oral toxicity in male and female Sprague-Dawley rats (Cognis, Food and Drug research laboratories, 1985). The test article was administered by gavage to each of ten rats at a level of 5.0 g/kg Body weight. One animal died by study day 2 following administration of the test article. All other animals survived the 15-day observation period. Diarrhea was observed at all animals but no unusual body weight development was observed. Some animals had also salivation and wet abdomen. Necropsy revealed no noteworthy findings. Based on this result , the acute oral LD50 of the test article is considered to be greater than 5.0 g/kg body weight.


A further study was conducted to assess the single oral toxicity of TMPeoTA in rats using the standard acute method (Cytec, Bio/Dynamics, 1984). Therefore 2 Groups of 6 animals/dose (sex unspecified) received a single oral dose of 500 or 5000 mg/kg. Parameters evaluated included survival and clinical observations for 7 days post-dosing. No signs of toxicity were noted at the dose level of 500 mg/kg bw. However, at 5000 mg/kg bw extreme faecal staining was noted on day 1 in all surviving rats. Three of the six animals died at this dose level.  In conclusion, the single oral median lethal dose (LD50) of TMPeoTA in rats was determined to be >500 mg/kg bw.


 


Dermal:


Studies according to other protocols:


A study was conducted to evaluate the acute dermal toxicity of ethoxylated trimethylol propane triacrylate (TMPeoTA) in albino rabbits (Cytec, Bio/Dynamics, 1984). A dermal application of 13,200 mg/kg TMPeoTA was applied to 4 rabbits. Parameters evaluated included mortality, clinical observations and body weight for a period of 7 days. No mortality was observed. Lack of food consumption was reported in one animal on days 5 and 6. In conclusion, the single dermal median lethal dose (LD50) of TMPeoTA was determined to be >13200 mg/kg bw in rabbits.


 


Assessment of acute toxicity:


Oral: All study results point to acute oral toxicity above 2000 mg/kg bw. Therefore a very low acute toxicity is assumed.


Dermal: The information available for the available acute dermal toxicity study points to very low dermal toxicity.


Inhalation: No acute inhalation study available


 


Key study assignment:


Oral: There a few studies available assessing the acute oral toxicity. All study result point to the same result, but only one study is conducted according to OECD guideline under GLP (Cray Valley, Huntingdon, 1998). As this study is also the latest conducted and very well documented study this study is assigned as key study.


Dermal: As there is only one relevant and reliable study available assessing the dermal toxicity this study (Cytec, Bio/Dynamics, 1984) has been used as key study.


Inhalation: No acute inhalation study available

Justification for classification or non-classification

The available data for ethoxylated trimethylolpropane triacrylate (TMPeoTA) indicate a low acute toxic potential. As the oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats and the acute dermal LD50 is above 13,200 mg/kg bw, no classification is derived. No information on inhalation toxicity is available which can lead to classification, therefore a classification for this endpoint is not possible.

In summary TMPeoTA it is not classified according to the GHS (Regulation (EU) 1272/2008).

Labelling for acute toxicity:

GHS: no classification