Registration Dossier

Administrative data

Description of key information

All available acute oral toxicity studies within this category resulted in acute oral LD50 > 5000 mg/kg bw. 
All available acute inhalation toxicity studies within the category resulted in acute inhalation LC50 > 5.05 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

The category covers fatty acid polyesters of polyols (Trimethylolpropane (TMP) or Pentaerythritol (PE)) mixed with adipic acid. The category contains UVCB substances with fatty acid carbon chain lengths from C8-C18 (even-numbered, including linear saturated and unsaturated chains) building mono-, di-,tri- or higher esters with TMP or PE respectively in variable proportions.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable read across data within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Endpoint specific data matrix:

ID #

Identifier

Acute toxicity: Oral

Acute toxicity: Inhalation

Acute toxicity: Dermal

1

CAS 95912-89-3 (a)

Experimental result
LD50 >5000 mg/kg bw

Experimental result
LD50 (4h) >5.05 mg/L air

--

2

CAS 91001-61-5

RA: CAS 95912-89-3
RA: EC 921-836-0

RA: CAS 95912-89-3
RA: EC 921-836-0

--

3

EC 921-836-0

Experimental result
LD50 > 5000 mg/kg bw

Experimental result
LD50 (4h) >5.06 mg/L air

--

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

Only for these substances a full set of experimental results and/or read-across is given.

Acute toxicity / Discussion

Acute oral toxicity

CAS 95912-89-3

An acute oral toxicity study was performed with Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) under conditions of GLP and according to the up-and down method described in OECD guideline 425 (Colas, 2010). In this experiment, 3 female Sprague Dawley rats were treated with the test substance via gavage at a limit dose of 5000 mg/kg bw. In none of the sequentially tested animals, mortalities and clinical signs of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was noted. Macroscopic and microscopic examinations did not reveal any treatment-related findings.

Based on these data, an oral LD50 > 5000 mg/kg bw was derived for Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane.

 

EC (EINECS) 921-836-0

In a GLP-compliant gavage study investigating the acute oral toxicity of Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol (EC 921-836-0), female Sprague Dawley were exposed to a limit dose of 2000 mg/kg bw in a stepwise procedure (3 rats per step) according to OECD guideline 423 (Freli, 2012). In two steps of treatment, no mortality and no clinical signs of toxicity were observed up to the end of the14-day observation period. All animals showed the expected gain in body weights during the study. At gross pathology, slight mucous enteritis of the intestinal tract was observed in 1 animal during the first step of treatment. In contrast, no abnormalities were noted in animals during the second step of treatment.

Based on the results, the oral LD50 value for Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol was > 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance may be considered to > 5000 mg/kg bw.

 

Acute inhalation toxicity

CAS 95912-89-3

In a GLP-conform study according to OECD guideline 403, the acute inhalation toxicity of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) was investigated in Crl:CD(SD) rats (Haferkorn, 2012). Using a nose only exposure system, the 5 male and 5 female animals were exposed to the test aerosol at an analytical atmosphere concentration of 5.05 mg/L air (5050 mg/m³ air) for 4 h. No mortality occurred during the 14-day observation period. Clinical signs of toxicity included slight ataxia, slight tremor and slight dyspnoea immediately until 30 min or 3 h after end of exposure in all male and female animals. Body weights were not adversely affected by treatment and the expected weight gain was observed in all animals during the course of the study. At necropsy, no pathological findings were observed.

Based on these results, the LC50 value for Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane was considered to be > 5.05 mg/L air.

 

EC (EINECS) 921-836-0

The acute inhalation toxicity of Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol (EC 921-836-0) was studied in rats according to EU Method B.2 and in compliance with GLP (Reminghaus, 1976). A group of 5 male and 5 female rats was exposed to an analytical atmosphere concentration of the test aerosol of 5.06 mg/L air (5060 mg/m³ air) for 4 h using a nose only exposure system. No mortality was observed in any of the animals during the study. Clinical signs of toxicity occurred immediately following exposure with the test substance and involved irregular respiration in male and female rats. However, all animals recovered from this symptom by SD 3 and appeared active and healthy for the remainder of the 14-day observation period. On SD 1, a lost in body weight or no body weight gain was observed in 9/10 animals, whereas thereafter all animals showed a continued weight gain through Day 14 of the study period. At necropsy, no abnormalities were noted.

Based on these results, the LC50 value for Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol is > 5.06 mg/L air.

Conclusion for acute toxicity

In summary, two studies are available studying the acute oral toxicity of PFAE mixed and branched category members resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available for this category showing LC50 values greater than 5 mg/L of the test aerosol. Taking into account the MW (>>500), the high log Pow values (>>5.7) and poor water solubility (<1 mg/L) dermal absorption rates for all category members are expected to be low, thus acute dermal toxicity is not anticipated.

Therefore, the available data indicate a very low level of acute toxicity for the category members and thus no hazard for acute oral, inhalation and dermal toxicity was identified.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR. 

Justification for classification or non-classification

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the PFAE mixed and branched category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, all available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.