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Description of key information

There are valid study data available to assess the acute oral, dermal and inhalation toxicity of trimethylolpropane triacrylate (TMPTA).

Oral:

Studies according to other protocols:

In a BASF company study report (BASF 1980, Gelbke H. P.) TMPTA dissolved in 0.5%carboxymethyl cellulose(10.0; 6.8; 4.6 and 3.2 g/kg bw) was administered via gavages to 10 (5m; 5f) rats. Mortality, clinical signs and bodyweight was examined 1h, 1d, 2d, 7d, 14d after application. In result a LD50 of 3680 mg/kg bw was calculated after 14 days.

Another study was conducted to assess the single dose toxicity of trimethylolpropane triacrylate (TMPTA) in Sprague-Dawley rats using the standard acute method (Cytec, Bionetics, Hart E. R. 1972). Groups of 5 Sprague-Dawley rats/dose (sex unspecified) received a single oral (gavage) dose of 50.0, 127.5, 315.1, 785, 1999, 5000 mg/kg TMPTA. The three lower doses were administered as 10% suspensions stabilized by the incorporation of 5% acacia, while the three higher doses were administered undiluted. Parameters evaluated included survival and clinical observations on the day of dosing and at least daily thereafter for 14 d. No mortalities were observed except in two of the five animals in the 5000 mg/kg bw group. In conclusion, the single oral median lethal dose (LD50) TMPTA in rats was calculated to be > 5000 mg/kg bw.

 

Assessment:

As both available studies indicate a LD50 above 2000 mg/kg bw only a low degree of oral acute toxicity is expected.

 

Key study assignment:

Because the report of the BASF study is written in German,the BASF study(1980)is used as supporting study. The well-conducted documentation of the Bionetics study(1972a)assigns this study as key study.

Dermal:

Studies according to other protocols:

The acute dermal toxicity of TMPTA was determined using 6 Sprague Dawley rats (BASF 1981, Jäckh). All rats received a dosage of 2000mg/kg bw applied on a 50cm2area on the shaved back/flank. After 24h exposure the test item was removed. Observation was carried out for 14 days. One of the used animals died on day 1 all other survived the treatment. General intoxication symptoms could (apathy,dyspnoea, bad general condition) be observed for some animals. Necropsy shows no unusual findings for the surviving animals, whereas the early died animal shows ulceration of the glandular stomach and acute dilation of the heart chamber. Local findings like redness and oedema could be observed for all treated animals. Based on this study the mean lethal dose for 14 days was determined as > 2000 mg/kg.

Another study was conducted to evaluate the acute dermal toxicity TMPTA in rabbits (Cytec, Litton Bionetics 1972, Hart E. R.). Therefore, sixteen albino rabbits were prepared by careful removal of the hair with electric clippers. Planned areas of application were identified and in half of the animals the area was lightly abraded. After weighing the animal, the calculated dose was applied, and the entire area covered with a rubber dam, held in place by tape. The dose levels applied were 0.315, 0.795, 1.99 and 5.0 mL/kg bw TMPTA. Four animals were included in each dose group. 24 h later, the binders were removed, and an effort made to remove any remaining material from the skin surface. A score of the local effects, according to the method of Draize, was recorded. The animals were observed repeatedly for seven days at the end of which time they were killed, and necropsy was performed. One mortality was observed at dose levels 1.99 and 5.0 mL/kg bw. In some cases, TMPTA caused no erythema or oedema, but in others caused severe effects. The author concludes that, the single dermal median lethal dose (LD50) of TMPTA was determined to be 4.7 mL/kg bw (i. e. 5170 mg/kg bw) in rabbits.

 

Assessment:

As both available studies indicate a LD50 above 2000 mg/kg bw no dermal acute toxicity hazard is expected.

 

Key study assignment:

Both studies were well conducted and met general accepted scientific principles. Both study results points to the same hazard range (classification).Because the BASF study(1981)is only available in German, the Cytec study(1972b)is used as key study.

Inhalation:

Studies according to other protocols:

The acute inhalations toxicity risk of TMPTA was determined with Sprague Dawley rats according to H. F. Smyth et al: Am. Ind. Hyg. Ass. J. 213, 95-107 (1962) (BASF 1980, Klimisch H. J.). Therefore,rats were exposed up to 7 h against a vapour pressure saturated test atmosphere. In result,all animals survived the highest exposure time (7h) without symptoms or unusual section findings.

Another study was conducted to evaluate the acute inhalation toxicity TMPTA in rats (Cytec, Industrial Bio-test 1976, Goode J. W.). Therefore 5rats/sex were exposed to the vapour of TMPTA at a single concentration of 0.55 mg/L air (nominal) for 6 h followed by and observation period of 14 days. Body weight was measured during the observation period and necropsy was performed at the end of this period.

There were no reactions noted during exposure or during the 14-day observation period. The average body weight gains were within the normal limits. Necropsy, performed on all rats at the end of the observation period, did not reveal any gross pathologic alterations. In conclusion, the single median lethal inhalation (LC50) of TMPTA was determined to be greater than 0.55 mg/L after 6 h exposure in rats.

Assessment:

As there was no increased in mortality found when TMPTA is applied to the rodents at saturation concentration, no inhalation toxicity hazard derives from vapour exposure from these study results.

 

Key study assignment:

Both studies were found to be satisfying to meet general scientific accepted principles, but both were less in documentation and did not follow a guideline. The BASF study report(1980)is only available in German and some important information are missing. But both studies were used as information source. Nevertheless, as only,the Cytec study(1976)is sufficient in documentation for risk assessment;values deriving from this study are used for risk assessment.However,none of the studies is used as key study.

 

The following information is taken into account for any hazard / risk assessment:

Oral:

Acute oral toxicity, rats, company protocol: LD50 (oral, rat) = 3680 mg/kg bw (BASF 1980, Gelbke, H. P.)

Acute oral toxicity, rats, company protocol: LD50 (oral, rat) >5000 mg/kg bw (Cytec, Bionetics, Hart E. R., 1972)

 

Inhalation:

Acute inhalation toxicity, rats, company protocol LC50 (inhalation, 6h, rat) > 0.55 mg/L (saturation) (Cytec, Industrial Bio-test 1976, Goode J. W.)

 

Dermal:

Acute dermal toxicity, rats, company protocol: LD50 (dermal, rat) > 2000 mg/kg bw (BASF 1981, Jäckh)

Acute dermal toxicity, rabbits, company protocol: LD50 (dermal, rabbit) > 5170 mg/kg bw (Cytec, Litton Bionetics 1972, Hart E. R.)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 680 mg/kg bw
Quality of whole database:
Two studies available (key and supporting), both with a klimisch score of 2.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
550 mg/m³
Quality of whole database:
Two studies available (both weight of evidence) with a klimisch score of 2 and 3. No toxicity observed i.e. LC50 > 0.55 mg/L ( > 550 mg/m³)

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Two studies available (key and supporting), both with a klimisch score of 2. Low toxicity i.e. LD50 > 2000 mg/kg bw

Additional information

Justification for classification or non-classification

The available data for TMPTA indicate a low acute toxic potential.

As the LD50 (rat) for acute oral toxicity and for acute dermal toxicity is determined above 2000 mg/kg bw TMPTA has not to be classified as acute dermal toxic or acute oral toxic according to GHS (Regulation (EU) 1272/2008) and also not to be classified according to DPD (67/548/EEC).

An acute inhalation toxicity test reveals no deaths in the highest administered concentration (LC0 = 0.55mg/L). This concentration reflects the maximum vapour concentration (saturation concentration). Based on the physical properties the maximum attainable concentration for the vapour is reached therefore the substance has to not to be classified for acute inhalation toxicity according to GHS (Regulation (EU) 1272/2008) and DPD (67/548/EEC) based on the results of vapour inhalation.

Classification for oral, inhalation and dermal toxicity:

GHS: Acute tox 5, H303 (May be harmful if swallowed)

CLP (EC 1272008): no acute toxicity classification for any exposure route