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Description of key information

Guideline studies on the acute oral toxicity (OECD Test Guideline 401) and on the inhalation toxicity (OECD Test Guideline 403) of formic acid in the rat are available. In accordance with test guidelines, the dermal toxicity was not examined because of the corrosive properties of formic acid. Pentaerythritol and propylidynetrimethanol are demonstrated to be of very low acute toxicity by all routes investigated. Similar low acute toxicity is predicted for their respective esters. The acute toxicity of the reaction mass of 2,2 -bis(formyloxymethyl) propane-1,3-diyl diformate and formic acid is therefore driven by the main component: formic acid

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 237 mg/kg bw
Quality of whole database:
Klimisch score = 1. Modern study compliant with current test guidelines and GLP

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
12.4 mg/m³
Quality of whole database:
Klimisch score = 1. Modern study compliant with current test guidelines and GLP

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid consists of formic acid, propylidynetrimethanol-esters and pentaerythritol-esters. The toxicity of the propylidynetrimethanol-esters and pentaerythritol-esters is predicted to be comparable to propylidynetrimethanol and pentaerythritol respectively. Acute toxicity data on formic acid, propylidynetrimethanol and pentaerythritol are considered appropriate to meet the REACH Annex VII-X data requirements for the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid.

 

Formic acid

The toxicity of formic acid depends on its corrosive properties. The acute oral toxicity of formic acid has been determined in rats in a study conducted according to OECD Test Guideline 401 (Huels, 1985). The acute oral LD50 of undiluted formic acid in male and female rats was 730 mg/kg bw. The acute inhalation toxicity of formic acid has been determined in rats in a study conducted according to OECD Test Guideline 403 in which animals were exposed via the whole body to vapours (BASF, 1980). The 4 hr LC50 was 7.4 mg/l (7400 mg/m3) in male and female rats. Clinical signs observed in the study indicated corrosive properties of the test substance, evidenced by the occurrence of corneal opacity and corrosion of the dorsal nose in some cases. The symptoms persisted until termination 14 days after the rats were exposed to 6.6 mg/L or above.

 

Propylidynetrimethanol

 The oral LD50 in rats was determined to be 14700 mg/kg bw in an acute oral toxicity study conducted prior to the implementation of official testing guidance but comparable to OECD Test Guideline 401 (Celanese Corporation, 1956). The acute inhalation toxicity of propylidynetrimethanol has been assessed in a pre-guideline study comparable to OECD Test Guideline 403 in which 20 male rats were exposed to vapours of propylidynetrimethanol at 850 mg/m3via whole body inhalation for 4 hours and observed for 14 days (Bayer 1965). No mortalities or clinical signs of toxicity were reported up to an including the highest exposure level of 850 mg/m3. The 4 hour LC50could not be determined exactly and was considered to be > 850 mg/m3.

 

Pentaerythritol

 In an acute oral toxicity study conducted according to OECD Test Guideline 401, the LD50 was determined to be greater than 5100 mg/kg for male and female rats (Berthold, 1990).  Keplinger & Kay (1964) reported that exposure of rats to 11 g/m³ pentaerythritol dust for a single 6 hour period caused no adverse effects. The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid. Guideline studies on the acute oral toxicity (OECD 401) and on the inhalation toxicity (OECD 403) of formic acid in the rat are available. Studies on the acute dermal toxicity of formic acid have not been due to the corrosive properties of the substance. The acute dermal toxicity of formic acid is generally relatively low, but there are case reports of severe intoxications following the accidental exposure of large skin areas to concentrated formic acid (cf. section 7.10). The dermal toxicity of the salts is low, e. g. LD50of sodium formate was >2000 mg/kg. The acute dermal toxicity of propylidynetrimethanol and pentaerythritol are low (respective LD50values are > 5000 mg/kg). The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid contains formic acid at concentrations up to 59% w/w. Testing is not scientifically justified in accordance with REACH Annex VII no. 8.5 column 2, since the substance is classified as corrosive to skin on the basis of the formic acid content. 

Pentaerythritol and propylidynetrimethanol are demonstrated to be of very low acute toxicity by all routes investigated. Similar low acute toxicity is predicted for their respective esters. The acute toxicity of the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid is therefore driven by the main component: formic acid.

 Justification for selection of acute toxicity – oral endpoint The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid consists primarily of formic acid, propylidynetrimethanol-esters and pentaerythritol-esters. The acute oral toxicity of the substance is determined by formic acid (read-across to studies on propylidynetrimethanol and pentaerythritol suggests that their esters have comparable low acute oral toxicity). Based on a formic acid content of up to 59% w/w and an LD50 of 730 mg/kg bw/day, the acute toxicity estimate for the substance was determined to be 1237 mg/kg bw/day. Justification for selection of acute toxicity – inhalation endpoint The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid consists primarily of formic acid, propylidynetrimethanol-esters and pentaerythritol-esters. The acute inhalation toxicity of the substance is determined by formic acid (read-across to studies on propylidynetrimethanol and pentaerythritol suggests that their esters have comparable low acute inhalation toxicity). Based on a formic acid content of up to 59% w/w and a 4 hour LC50 of 7.3 mg/L, the acute toxicity estimate for the substance was determined to be 12.4 mg/L. Justification for selection of acute toxicity – dermal endpoint According to REACH Annex VII No. 8.5 column 2, testing is not required since the substance is classified as corrosive to skin on the basis of the formic acid content

Justification for classification or non-classification

The toxicity of formic acid can be attributed to its corrosivity. Based on available data, pentaerythritol and propylidynetrimethanol have low acute toxicity via the oral, dermal and inhalation routes. Similar low acute toxicity is predicted for their esters. The acute toxicity of the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid is therefore driven by formic acid. The reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid contains formic acid at concentrations up to 59% w/w, with propylidynetrimethanol-esters and pentaerythritol-esters at lower concentrations (> 10%) and impurities (< 10%).  Classification for the acute oral toxicity of the substance is proposed based on the additivity formula in Section 3.1.3.6 of EC Regulation 1272/2008. Acute oral LD50 values for propylidynetrimethanol and pentaerythritol were determined to be > 2000 mg/kg bw, indicating that the respective esters of these substances are of low acute oral toxicity. Based on a concentration of 59% w/w and an acute oral LD50 value of 730 mg/kg bw/day for formic acid, the acute toxicity estimate (ATE) for the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid is determined to be 1237 mg/kg bw/d. The substance meets the criteria for classification as Category 4 Harmful if swallowed (H302) according to EC Regulation 1272/2008.

Based on a concentration of 59% w/w and an acute inhalation LC50 of 7.3 mg/L for formic acid vapour, the acute toxicity estimate (ATE) for the reaction mass of 2,2-bis(formyloxymethyl)propane-1,3-diyl diformate and formic acid is determined to be 12.4 mg/L. The substance meets the criteria for classification as Category 4 Harmful if inhaled (H332) according to EC Regulation 1272/2008. The additional hazard statement EH071 Corrosive to the respiratory tract must be used since the inhalation toxicity results from the corrosivity of formic acid.