Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP, category approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, category approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 2.916 mg/L air (OECD 403, category approach)

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 adverse effect observed

Additional information

Justification for grouping of substances and read-across

The Glycol ester category covers esters of an aliphatic diol (ethylene glycol (EG), propylene glycol (PG) or 1,3-butyleneglycol (1,3-BG)) and one or two carboxylic fatty acid chains. The fatty acid chains comprise carbon chain lengths ranging from C6 to C18, mainly saturated but also mono unsaturated C16 and C18, branched C18 and epoxidized C18.

 

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 and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

 

Acute Toxicity

Data Matrix

CAS

91031-31-1 (b)

111-60-4

624-03-3 (a)

627-83-8

151661-88-0

31565-12-5

68583-51-7

853947-59-8

84988-75-0

4219 -49 -2 

Acute toxicity oral

RA: CAS 627-83-3

RA: CAS 68583-51-7

RA: CAS 111-60-4

LD50 (rat) > 2000 mg/kg bw

RA: CAS 627-83-8

RA: CAS 68583-51-7

LD50 (rat) > 5000 mg/kg bw

LD50 (rat) > 2000 mg/kg bw

--

LD50 (rat) > 2000 mg/kg bw

--

RA: CAS 627-83-3

RA: CAS 68583-51-7

RA: CAS 151661-88-0

 

RA: CAS 627-83-3

RA: CAS 68583-51-7

RA: CAS 111-60-4

 

Acute toxicity inhalation

RA: CAS 68583-51-7

--

RA: CAS 68583-51-7

RA: CAS 68583-51-7

--

--

LC50 (rat, guinea pig)> 200 ppm

--

RA: CAS

68583-51-7

 

Acute toxicity dermal

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

--

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

LD50 (rat) > 2000 mg/kg bw

LD50 (rat) > 2000 mg/kg bw

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA from CAS 31565-

LD50 (rat) > 2000 mg/kg bw

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-

  

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

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

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

 

Acute oral toxicity

CAS 627-83-8

The acute toxicity via the oral route of ethylene distearate has been investigated in rats and mice in several studies (CAS 627-83-8).

A study for acute oral toxicity of ethylene distearate was performed in rats in accordance with OECD guideline 401 (Wnorowski, 1991a). A group of 10 Wistar rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance in carboxymethyl cellulose by gavage. The observation period following administration was 14 days. During the study period, no mortality and no clinical signs of toxicity were observed in any animal. All test animals showed normal body weight gain. Therefore, the oral LD50 in male and female rats was greater than 5000 mg/kg bw.

 

Further studies in which the acute oral toxicity of ethylene distearate was studied in rats and mice similar to OECD guideline 401 are available. The test material was administered by gavage at doses of 5000 or 2000 mg/kg bw (Wnorowski, 1991; Bouffechoux, 1995) and . No mortalities were observed and no abnormalities in body weight were recorded during the 14-day observation period in the studies. No signs of toxicity were observed in the studies by Bouffechoux and Wnorowski (1995, 1991).

Furthermore, four independent acute oral toxicity studies in doses up to 16000 mg/kg bw in rats with glycol distearate are reported (Elder, 1982). Doses above 13000 mg/kg bw were noted to produce diarrhoea, wet oily coats and nasal haemorrhage being reversible within 10 days. In one study, at gross necropsy the stomach contained residues which appeared to be the test material.

In summary, the oral LD50 of ethylene distearate is greater than 5000 mg/kg bw.

 

CAS 68583-51-7

Several studies investigating the acute toxicity via the oral route of Decanoic acid mixed diesters with octanoic acid and propylene glycol are available (CAS 68583-51-7).

 

A study for acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was performed in rats in accordance with EU Method B.1 under GLP conditions (Potokar, 1988). A group of 10 Wistar rats (5 males and 5 females) was dosed with 2000 mg/kg bw of the test material in peanut oil by gavage. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. No effect on body weight was noted. During necropsy, in 1/5 males a tightly filled urinary bladder and in 1/5 females a mild hydrometra was observed. These findings were not considered to be substance-related. Therefore, under the conditions of this study, the oral LD50 in male and female rats was greater than 2000 mg/kg bw.

 

Further studies are available, in which the acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was studied in rats and mice according to OECD guideline 401.

 

In each case, the test material was administered by gavage at a dose of 5000 mg/kg bw or 5 mL/kg bw (Blackwell, 1989; Blackwell, 1988; Consultox Laboratories Ltd., 1972; Masson, 1985). No mortalities were observed during the 14-day study periods. No substance related signs of toxicity were observed in the studies. Moreover, no abnormalities in body weight (gain) were observed during the observation period and macroscopic examinations at termination revealed no treatment-related changes (Blackwell, 1989; Blackwell, 1988).

 

In summary, the oral LD50 of Decanoic acid mixed diesters with octanoic acid and propylene glycol is greater than 2000 mg/kg bw.

 

CAS 111-60-4

The acute toxicity via the oral route of ethylene glycol monostearate has been investigated in rats and mice (CAS 111-60-4).

An acute oral toxicity study was performed similar to OECD guideline 401 as a limit test (Gloxhuber, 1982). 5 male and 5 female Wistar rats were treated with a single dose of 2000 mg/kg bw of ethylene glycol monostearate (CAS No. 111 -60 -4). Animals were observed for 14 days and no clinical signs or mortalities reported. Body weights and gross necropsy revealed no abnormal findings as well. Therefore the LD50 for ethylene glycol monostearate in Wistar rats was set to be > 2000 mg/kg bw.

In an acute oral toxicity study similar to OECD guideline 402, 5 male NMRI mice were treated with a single dose of 2000 mg/kg bw of the read across substance 2-hydroxyethyl stearate (CAS 111-60-4) in a limit test (Dufour, 1994). No mortalities or any clinical signs occurred. Body weight and necropsy revealed no abnormal findings. Therefore the LD50 mouse was set to be > 2000 mg/kg bw.

 

CAS 151661-88-0

A study for acute oral toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) is available (Potokar, 1989). The study was performed equivalent to OECD guideline 401 under GLP conditions in a group of 10 Wistar rats (5 males and 5 female), treated with the limit dose 2000 mg/kg bw of the test substance in peanut oil by gavage. No mortality occurred and no clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed. No effect on body weight was noted and pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Therefore, under the conditions of this study, the oral LD50 in male and female rats was greater than 2000 mg/kg bw.

 

 

Acute inhalation toxicity

CAS 68583-51-7

For acute inhalation toxicity, two studies are available within the Glycol ester category and were considered for assessment of all category members by read-across and a weight of evidence approach. The acute inhalation toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) was evaluated in two studies similar to OECD guideline 403 in a limit test (Re, 1978 a,b). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs and 3 control animals, respectively, were exposed whole body to 200 ppm (equivalent to 2.916 mg/L air) for 6 h. The animals were observed for a period of 7 days following administration.

No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. Necropsy revealed no substance-related findings in both studies.

Therefore, the LC50 for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L).

 

Acute dermal toxicity

CAS 151661-88-0

Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was evaluated in rats equivalent to OECD guideline 402 under GLP conditions (Potokar, 1989). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under occlusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted.

 

CAS 853947-59-8

Butylene glycol dicaprylate/dicaprate (CAS 853947-59-8) was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Mürmann, 1992a). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under semiocclusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted.

 

CAS 31565-12-5

Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS 31565-12-5) was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Mürmann, 1992b). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under semiocclusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted. In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point.

 

The results of the three studies of the category substances consistently showed no effects at the limit dose 2000 mg/kg bw. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw. 

 

Conclusion for acute toxicity

In summary, 15 studies are available studying the acute oral toxicity of Glycol Ester category members resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available within the Glycol Ester category. From these studies a LC50 value for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L) was obtained. Acute dermal toxicity data from three category members consistently showed no effects at the limit dose 2000 mg/kg bw.

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

For a detailed reference list please refer to the CSR or IUCLID section 13.

 

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 Glycol Ester Category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on acute oral and dermal 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.

Since the available acute inhalation studies provided LC50 values for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L), the data is inconclusive according to the classification criteria of Regulation (EC) 1272/2008 or Directive 67/548/EEC.