Registration Dossier

Administrative data

Description of key information

All available acute oral toxicity studies within this category resulted in an acute oral LD50 > 2000 mg/kg bw. 
All available acute dermal toxicity studies within the category resulted in acute dermal LD50 > 2000 mg/kg bw.
All available acute inhalation toxicity studies within the category resulted in acute inhalation LC50 > 5.0 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 adverse effect observed

Additional information

Justification for grouping of substances and read-across

The polyol esters category comprises of 51 aliphatic esters of polyfunctional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The category contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C28, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9,branched C14 – C22 building mono-, di-, tri-, and tetra esters with an alcohol (i.e.polyol).

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 7.1 and 13) and within Chapter 5.1 of the CSR.

 

Data matrix for acute toxicity

CAS

Acute toxicity oral

Acute toxicity inhalation

Acute toxicity dermal

NPG esters

68855-18-5 (a)

LD50 > 2000 mg/kg bw

LC 50 > 5.22 mg/L air

Waiver

31335-74-7

LD50 > 2000 mg/kg bw

RA: CAS 68855-18-5

RA: CAS 85711-80-4

RA: CAS 68855-18-5

Waiver

67989-24-6 (b)

LD50 > 2000 mg/kg bw

--

--

85711-80-4

LD50 > 2000 mg/kg bw

--

--

70693-32-2

RA: CAS 97281-24-8

RA: CAS 68855-18-5

Waiver

former CAS 85186-86-3

RA: 85186-86-3

RA: CAS 68855-18-5

Waiver

85186-86-3

LD50 > 2000 mg/kg bw

 

RA: CAS 68855-18-5

Waiver

85186-95-4

RA: CAS 85711-80-4

RA: CAS 85005-25-0

RA: CAS 68855-18-5

Waiver

85116-81-0

RA: CAS 85711-80-4

RA: CAS 85005-25-0

RA: CAS 68855-18-5

Waiver

91031-27-5

RA: CAS 85711-80-4

RA: CAS 85005-25-0

RA: CAS 68855-18-5

Waiver

42222-50-4

LD 50 > 2100 mg/kg bw

 RA: CAS 67989-24-6

RA: CAS 68855-18-5

LD50 > 2000 mg/kg bw

85005-25-0

LD50 > 2000 mg/kg bw

RA: CAS 68855-18-5

Waiver

TMP esters

78-16-0 (a)

LD50 > 5000 mg/kgbw

LD50 > 2000 mg/kg bw

LC50 > 20 mg/L

RA: CAS 68424-31-7

LD50 > 2000 mg/kg bw

91050-88-3 (b)

RA: 85186-89-6

RA: CAS 68424-31-7

RA: CAS 11138-60-6

97281-24-8

LD50 > 2000 mg/kg bw

--

--

11138-60-6

LD50 > 2000 mg/kg bw

RA: CAS 68424-31-7

LD50 > 2000 mg/kg bw

91050-89-4

LD50 > 2000 mg/kg bw

RA: CAS 68424-31-7

RA: CAS 11138-60-6

85566-29-6

RA: 85186-89-6

RA: 403507-18-6

RA: 91050-90-7

RA: CAS 68424-31-7

RA: CAS 68855-18-5

RA: CAS 11138-60-6

(Formerly 85186-89-6)

LD50 > 2000 mg/kg bw

RA: CAS 68424-31-7

RA: CAS 11138-60-6

403507-18-6

LD50 > 2000 mg/kg bw

--

LD50 > 2000 mg/kg bw

68002-79-9

RA: 85005-23-8

RA: 403507-18-6

RA: 91050-90-7

RA: CAS 68424-31-7

RA: CAS 68855-18-5

RA: CAS 11138-60-6

(Formerly 85005-23-8)

EC 931-531-4

LD50 > 2000 mg/kg bw

RA: CAS 68424-31-7

RA: CAS 11138-60-6

91050-90-7

LD50 > 2000 mg/kg bw

--

--

68002-78-8

RA: CAS 85186-89-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 68855-18-5

RA: CAS 403507-18-6

(Formerly 57675-44-2)

EC 931-461-4

LD50 > 2000 mg/kg bw

RA: CAS 68424-31-7

RA: CAS 11138-60-6

85186-92-1

RA: (Formerly 57675-44-2)

EC 931-461-4

RA: (Formerly 85005-23-8)

EC 931-531-4

RA: CAS 68424-31-7

RA: CAS 68855-18-5

RA: CAS 11138-60-6

RA: CAS 403507-18-6

68541-50-4

RA: CAS 85186-89-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 68855-18-5

RA: CAS 403507-18-6

PE esters

15834-04-5 (b)

RA: CAS 67762-53-2

RA:68424-31-7
RA: 85116-93-4

RA: CAS 67762-53-2

RA: CAS 68424-31-7

 

RA: CAS 71010-76-9

85116-93-4

LD50 > 2000 mg/kg bw

RA:68424-31-7RA: CAS 19321-40-5

 

RA: CAS 67762-53-2

RA: CAS 85536-35-2

RA: CAS 62125-22-8

85711-45-1 (a)

RA: CAS 19321-40-5
RA: CAS 85186-89-6
RA: CAS 85116-93-4

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8

25151-96-6

RA: CAS 19321-40-5

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8

67762-53-2

LD50 > 2000 mg/kg bw

LC50 > 5.50 mg/L

RA: CAS 71010-76-9

(Formerly 68441-94-1)

RA: CAS 71010-76-9

RA: 68424-31-7

RA: 85116-93-4

RA: CAS 67762-53-2

 

RA: CAS 68424-31-7

RA: CAS 71010-76-9

(Formerly 68424-30-6)

RA: CAS 71010-76-9

RA: 68424-31-7

RA: 85116-93-4

RA: CAS 67762-53-2

 

RA: CAS 68424-31-7

RA: CAS 71010-76-9

68424-31-7 (c)

LD50 > 2000 mg/kg bw

RA: CAS 67762-53-2

RA: 85116-93-4

RA: CAS 68424-31-7

RA: CAS 71010-76-9

68424-31-7 (d)

LD50 > 2000 mg/kg bw

RA: CAS 67762-53-2

RA: 85116-93-4

RA: CAS 68424-31-7

RA: CAS 71010-76-9

68424-31-7 (e)

LD50 > 2000 mg/kg bw

RA: CAS 67762-53-2

RA: 85116-93-4

RA: CAS 68424-31-7

RA: CAS 71010-76-9

71010-76-9

LD50 > 2000 mg/kg bw

RA: CAS 67762-53-2

LD50 > 2000 mg/kg bw

85586-24-9

LD50 > 4800 mg/kg bw

RA: CAS 71010-76-9

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 71010-76-9

85049-33-8

RA: 68424-31-7

RA: 85116-93-4

RA: CAS 85186-89-6

RA: CAS 67762-53-2

RA: CAS 68424-31-7

 

RA: CAS 71010-76-9

RA: CAS 62125-22-8

 

91050-82-7

RA: CAS 19321-40-5

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8

19321-40-5

LD50 > 2000 mg/kg bw

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8

68604-44-4

RA: CAS 19321-40-5
RA: CAS 85186-89-6

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8

62125-22-8

LD50 > 5000 mg/kg bw

RA: CAS 67762-53-2
RA: CAS 85536-35-2

LD50 > 2000 mg/kg bw

68440-09-5

RA: CAS 19321-40-5
RA: CAS 71010-76-9

RA: CAS 67762-53-2
RA: CAS 85536-35-2

RA: CAS 62125-22-8
RA: CAS 71010-76-9

85536-35-2

--

LC50 > 5.0 mg/L

--

(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 "--".

c) CAS 68434-31-7 – Lead registrant

d) Separate registration of CAS 68434-31-7

e) Separate registration of CAS 68434-31-7 (2-ethylhexanoic acid)

 

Discussion

Acute Oral Toxicity

There are several reliable acute oral toxicity studies available within the polyol esters category.

CAS 68855-18-5

An acute oral toxicity study with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was performed according to OECD Guideline 401 (standard acute method) and GLP (Doyle, 1996). In a preliminary study, the test item was administered by gavage to two Alderley Park albino rats (Alpk: APfSD) per sex at 2000 mg/kg bw (limit test). Five further animals per sex were then treated with the same dose for the main study. The animals were subjected to daily observations and determinations of body weights on test Days -1 (prior to fasting), 1, 3, between Days 4 and 6, and on Day 8 and 15. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 31335-74-7

A short summary of an acute oral toxicity study with 2,2-dimethyl-1,3-propanediyl dioctanoate (CAS 31335-74-7) is available (Robinson, 1993). No information is given on the guideline followed or on GLP compliance. However, it is stated that the study was performed as a limit test. Two rats per sex (strain not specified) were orally administered the test item via gavage at a dose of 2000 mg/kg bw. During the 8-day observation period the animals were subjected to daily observations and weighing on Days 1 and 8. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 67989-24-6

An acute oral toxicity study 9-octadecenoic acid (Z)-, ester with 2,2-dimethyl-1,3-propanediol (CAS 67989-24-6) was performed similar to OECD Guideline 401 (standard acute method, limit test) and in compliance with GLP (Potokar, 1988). The test item was administered by oral gavage to five Wistar rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days -1, 2, 7, and 14 and macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 85711-80-4

An acute oral toxicity study with 1,3-Propoanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-4) is available (Bouffechoux, 1995). No information is given on the guideline followed or on GLP compliance. However, it is stated that the study was performed as a limit test. Five female Swiss mice were orally administered the test item via gavage at a dose of 2000 mg/kg bw. During the 14-day observation period the animals were subjected to clinical observations and weighing. No necropsy was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted. The oral LD50 value in mice was determined >2000 mg/kg bw.

CAS 85186-86-3

An acute oral toxicity study with Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS 85186-86-3) was performed according to OECD Guideline 420 (fixed dose procedure, limit test) and GLP (Pooles, 2012). The test item was administered by gavage to five Wistar (RccHanTM:WIST) rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days 0, 7, and 14. Macroscopic and histopathologic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 42222-50-4

There is only one acute oral toxicity study with limited reporting available for 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4).

Supporting data are available for 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4). An acute oral toxicity study was performed similar to OECD Guideline 401 (standard acute method, limit test) but not in compliance with GLP (Weiß, no year reported). The test item was orally administered (not further specified) to five Wistar Unilever (HsdCpb: WV) per sex at a dose of 2100 mg/kg bw. During the 14-day observation period the animals were examined for clinical signs. No mortality occurred during the study period and no clinical signs of toxicity were observed up to study termination. The oral LD50 value in rats was determined >2100 mg/kg bw.

CAS 85005-25-0

An acute oral toxicity study with Neopentyl Glycol Diisostearate (Fatty acids, C14-18 and C18-unsatd., branched and linear, esters with neopentyl glycol) (CAS 85005-25-0) was performed according to OECD Guideline 401 (standard acute method) and GLP (Bien, 1993). The test item was administered by oral gavage to five Bor: WISW (SPF cbp) rats per sex at 2000 mg/kg bw (limit test). The animals were subjected to daily observations and weekly determination of body weights. Macroscopic examination was performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 78-16-0

An acute oral study was performed according to EU Method B.1 (limit test) and GLP, however only limited information about the test substance was given (Reijnders, 1987). The test substance was administered by gavage to male and female Wistar rats. In a pilot study one animal per sex was administered 1800, 3200 and 5000 mg/kg bw. In the main study five males and females received 5000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities and effects on body weight were observed in the pilot and main study. The oral LD50 value in rats was found to exceed 5000 mg/kg bw.

Another acute oral toxicity study was conducted comparable to OECD Guideline 401 (limit test) and GLP, again limited information about the test substance was given (Glaza, 1997). 5 male and female Crl:CD (SD)BR rats were exposed to 2000 mg/kg bw test substance by gavage. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No clinical signs or substance related abnormalities on body weights or at necropsy were observed. The LD50 was found to exceed 2000 mg/kg bw.

A second study performed comparable to OECD Guideline 401 is available (Robinson, 1991) but due to inacceptable restrictions this study is not considered for classification. Only 2 Alderley Park SPF albino rats per sex were exposed to the limit dose of 2000 mg/kg bw and observed for 8 days. Slight piloerection as minimal sign of toxicity was observed in male animals until Day 5. No signs of toxicity were observed in the females. The LD50 was found to exceed 2000 mg/kg bw.

Three studies are available which were conducted before adoption of OECD Guideline 401. However, all three studies were conducted comparable to this guideline. 5 male and female Wistar rats were exposed to the test substance (limit test) at concentrations of 5000 mg/kg bw (Morgareidge, 1974) and 15000 mg/kg bw (Moreno, 1977 and 1978). Animals were observed for clinical signs for 14 days. Necropsy at the end of the observation period was not performed. In the first study (Morgareidge, 1974) no substance related effects were observed following administration of 5000 mg/kg bw. One animal died after 7 days in the Moreno (1977) study and one animal showed ataxia and lethargy three hours after administration of 15000 mg/kg bw. In the second Moreno (1978) study no deaths were observed but all animals showed diarrhea on the day of administration. Additionally, some male and female animals showed lethargy and chromorhinorrhea and females had an oily body on Days 2 to 4 following application of 15000 mg/kg bw.

In summary, the LD50 for the test substance was found to exceed 15000 mg/kg.

CAS 97281-24-8

An acute oral toxicity study Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane (CAS 97281-24-8) was performed similar to OECD Guideline 401 (standard acute method, limit test) and in compliance with GLP (Potokar, 1988). The test item was administered by gavage to five Wistar rats per sex at a dose of 2000 mg/kg bw. The animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined weekly on test Days -1, 2, 7, and 14 and macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of toxicity were observed during the study period. No effects on body weights were noted. Necropsy revealed for males; haemangioma of the left renal lymph node in 1/5 animals, and mild hypoplasia of the right testis in 1/5 animals. 1/5 females showed high grade hydrometra and haemangioma of the left renal lymph node. The oral LD50 value in rats was determined >2000 mg/kg bw.

CAS 11138-60-6

A reliable acute oral toxicity study was conducted withFatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol according to OECD Guideline 401 (standard acute method, limit test). Upon treatment of male and female rats with 2000 mg/kg bw of the test substance no mortality or enduring adverse effect was observed during the 14 d observation period. The animals had normal weight gain until the end of the observation period (Clouzeau, 1990). The LD50 value was therefore determined to be > 2000 mg/kg bw.

 

CAS 91050-89-4

An acute oral toxicity study was performed with Fatty acids, C8-10, triesters with trimethylolpropane (CAS 91050-89-4) comparable to OECD 401 (limit test) (Kästner, 1983).Only limited documentation was available but all relevant data were given. The test substance was administered by gavage to 5 male and female Wistar rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. No treatment related clinical signs of toxicity were observed up to the end of the 14-day observation period. In addition no effect on body weight was noted. Thus, the oral LD50 value in rats was found to exceed 2000 mg/kg bw.

CAS 85005-23-8

An acute oral toxicity study was conducted according to OECD Guideline 423 (Acute Toxic Class Method). Upon treatment of male and female Wistar rats with 2000 mg/kg bw of the test substance no mortality or any adverse effect was observed during the 14 d observation period. The animals had normal weight gain until the end of the observation period (Busschers, 1997). The LD50 value was therefore determined to be > 2000 mg/kg bw.

 

Formerly CAS 85186-89-6

An acute oral toxicity study (limit test) with Fatty acids, C8-10(even), C14-18(even) and C16-18(even)-unsatd., triesters with trimethylolpropane (CAS 85186-89-6) was performed according to OECD Guideline 401 and GLP (Kuszewski, 1996). The test substance was administered by gavage at a concentration of 2000 mg/kg bw to groups of five male and female Hsd/Cpb:WU rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No clinical signs of toxicity, only slight changes in body weights for some animals and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

CAS 403507-18-6

An acute oral toxicity study with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) was performed comparable to OECD Guideline 423 (acute toxic class method, limit test) and under GLP conditions (Sanders, 2002). The test substance was administered by gavage to three Sprague-Dawley CD (Crl: CD IGS® BR) male and female rats at 2000 mg/kg bw. Animals were subjected to daily observations and weekly determination of body weight. Gross pathology examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities with regard to clinical signs, body weights and necropsy were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

CAS 91050-90-7

An acute oral toxicity study (limit test) with Fatty acids, C16-18, triesters with trimethylolpropane (CAS 91050-90-7) is available, which was performed according to EU Method B.1 and GLP (Potokar, 1989). The test substance was administered by gavage at a concentration of 2000 mg/kg bw to groups of five male and female Wistar rats. The animals were observed for 14 days following administration, body weights were determined weekly. No mortalities occurred during the study period. No clinical signs of toxicity, no changes in body weight and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

CAS 85116-93-4

An acute oral toxicity study (limit test) was conducted withFatty acids, C16-18 (even numbered), esters with pentaerythritol(CAS 85116-93-4) comparable to OECD Guideline 401 (Potokar, 1983). Reporting of test conditions and results was limited. The test substance was administered by gavage at a concentration of 2000 mg/kg bw to 2 male and female Wistar rats each. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No significant signs of toxicity except for transient rough fur and reduced activity direct after dosing were observed. Normal weight gain was observed after dosing. Finally no macroscopic findings were found at necropsy. The acute oral LD50 was found to be greater than 2000 mg/kg bw.

CAS 67762-53-2

The acute toxicity via the oral route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in two studies with rats (CAS No. 67762-53-2).

An acute oral toxicity study (limit test) was performed according to OECD Guideline 420 (fixed dose procedure) (Zolyniene, 1999). Groups of 5 males and females fasted CD Sprague-Dawley rats received single oral gavage doses of 2000 mg/kg bw. The animals were observed for 14 days following administration. No mortalities occurred. One animal showed alopecia extremities on snout which was not considered treatment related. No further clinical signs of toxicity were reported. No effect on body weight was noted. Finally necropsy revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (D’Aleo, 1984). The test substance was administered by gavage at a concentration of 15000 mg/kg bw to groups of 5 male and female Sprague-Dawley rats. The animals were observed for 14 days following administration. No mortalities occurred. All animals exhibited clear, oily perineal staining on the 1st, 2nd, and 3rd day following treatment. This condition normally regarded as an adverse effect, was considered to be a consequence of the high dose level administered and not considered a toxic sign. No further clinical signs of toxicity were reported. The acute oral LD50 was found to be greater than 15000 mg/kg bw.

In summary, the oral LD50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 2000 mg/kg bw.

 

CAS 68424-31-7

The study conducted with Fatty acids, C5-10, esters with pentraerythritol (CAS No.68424-31-7) (Robinson, 1991) with limitations (reduced animal number), revealed but revealed no mortality and no other toxic effects, but an initial weight loss after treatment of rats with 2000 mg/kg bw. However this effect was completely reversible and the animals showed subsequently normal body weight gain.

 

CAS 71010-76-9

An acute oral toxicity study with Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) was performed according to OECD Guideline 425 (up and down procedure, limit test) and GLP (Mallory, 2006). Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was administered by gavage to one female Sprague-Dawley rat at the starting dose of 2000 mg/kg bw. Since no mortality and no other toxic effects could be detected during the 14 day study period, 4 further female animals were equally dosed with 2000 mg/kg bw. No clinical signs of toxicity were observed up to the end of the 14-day observation period. No effect on body weight was noted. Finally, necropsy revealed non substance-related findings. The oral LD50 value in female rats was found to exceed 2000 mg/kg bw.

CAS 85586-24-9

An acute oral toxicity study (limit test) was conducted with Fatty acids, C8-10, tetraesters with pentaerythritol (CAS 85586-24-9) (Kästner, 1981). The test did not follow a specific guideline and was not GLP-compliant. Thus, only limited details were reported. The test substance was administered by gavage at a concentration of 5 mL/kg (4800 mg/kg bw) to 10 male Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. Ruffled fur and slight sedation was observed during the first 24 h after dosing. The acute oral LD50 was found to be greater than 4800 mg/kg bw.

CAS 19321-40-5

An acute oral toxicity study with Pentaerythritol tetraoleate (CAS 19321-40-5) was performed according to OECD Guideline 423 (acute toxic class method, limit test) and GLP (Pels Rijcken, 1997). Pentaerythritol tetraoleate was administered by oral gavage to three Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No treatment related abnormalities were observed. The oral LD50 value in rats was found to exceed 2000 mg/kg bw.

CAS 62125-22-8

The acute toxicity via the oral route of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) has been investigated in rats in three studies (CAS No. 62125-22-8).

Two acute oral toxicity studies (limit tests) were performed according to OECD Guideline 401 ((1) Debets, 1984, GLP-compliant; (2) Bouffechoux, 1997). The test substance was administered by gavage at a concentration of (1) 5000 mg/kg bw and (2) 5 mL/kg (corresponding to 4600 mg/kg bw, based on density of 0.92 g/mL) to groups of five male and female Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred. No clinical signs of toxicity, no changes in body weights and no differences at macroscopic examination were reported. The acute oral LD50 was found to be greater than (1) 5000 mg/kg bw and (2) 4600 mg/kg bw.

Another acute oral toxicity study (limit test) was performed comparable to OECD Guideline 401 (Sugar, 1981). The test substance was administered by gavage at a concentration of 10000 mg/kg bw (1.5 mL/100 g bw) to groups of five male and female CD rats. The animals were observed for 14 days following administration. No mortalities occurred. All the rats were hypoactive at the 4 h observation time point. No further signs of toxicity were noted during the study period. The acute oral LD50 was found to be greater than 10000 mg/kg bw.

In summary, the oral LD50 of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) is greater than 5000 mg/kg bw.

Acute Inhalation Toxicity

CAS 68855-18-5

For acute inhalation toxicity, one study is available within the NPG esters and was considered for assessment of all NPG esters and of two TMP esters and read-across was conducted based on a category and/or weight of evidence approach.

An acute inhalation toxicity study was performed with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECD Guideline 436 (acute toxic class method) under GLP conditions. Three RccHanTM:WIST rats per sex were exposed for 4 hours to 5.22 mg/L (mean achieved concentration) test substance aerosol by nose only inhalation (Griffiths, 2012). The test concentration was chosen based on the outcome of a preliminary test with two rats at a dose of 2.14 mg/L. In the main study, the animals were subjected to daily observations for clinical signs, and twice daily for morbidity and mortality. Body weights were determined prior to treatment and afterwards on test Days 1, 3, 7, and 14. After terminal sacrifice the animals were submitted to full external and internal observation. Detailed macroscopic examination of the respiratory tract was performed to determine signs of irritancy or local toxicity. No mortality occurred throughout the study period. Signs of hunched posture and pilo-erection were commonly seen in animals for short period on removal from the chamber following 4-h inhalation studies. Wet fur was commonly recorded both during and for a short period after exposure. These observations were considered to be associated with the restraint procedure and, in isolation, were not indicative of toxicity. In addition, an increased respiratory rate was noted in all animals. On removal from the chamber and 1 h post-exposure, all animals exhibited increased respiratory rate and ataxia. One day after exposure, all animals still showed increased respiratory rate and also hunched posture as well as occasional instances of pilo-erection. All animals recovered to appear normal from Days 5 to 8 post-exposure. All animals showed the expected body weight gain during the study, except for one female which not gained weight during the final week of the 14-day observation period. In addition, one male exhibited a slight loss in body weight on the first day of exposure. Necropsy revealed no treatment-related findings. The inhalation LC50 value in rats was determined >5.22 mg/L.

For acute inhalation toxicity, one study is available within the TMP esters. Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) and Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) were used for assessment of the TMP esters and read-across was conducted based on a category approach.

CAS 78-16-0

An acute inhalation toxicity study was performed with 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl] propane-1,3-diyl bisheptanoate (CAS 78-16-0). 5 male and female rats (strain not specified) were exposed for 1 hour to 20 mg/L test substance vapour (Anonimous, 1978). The test substance caused no clinical signs, body weight changes or abnormalities in necropsy during the 15 day study period. Only one animal died on day 14. The LC50 was therefore found to be greater than 20 mg/L air, however since the original report is not available and because of only one hour of exposure this study is found insufficient for hazard assessment.

For acute inhalation toxicity, three studies are available from the PE esters within the polyol esters category. Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7), Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) and Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS No. 67762-53-2) were used for assessment of the PE esters and read-across was conducted based on a category and/or weight of evidence approach.

CAS 67762-53-2

The acute toxicity via the inhalation route of Fatty acids, C5-9 tetraesters with pentaerythritol has been investigated in rats in two studies (CAS 67762-53-2).

The first study was conducted comparable to OECD Guideline 403 and according to GLP. 10 male and female Sprague-Dawley rats were exposed for 4 hours to 0.48 or 4.06 mg/L test substance aerosol by whole body inhalation exposure (Mekitarin, 1990). No mortality, clinical signs, body weight changes or abnormalities in necropsy were observed during the 15 day study period in any group. The LC50 was therefore found to be greater than 4.06 mg/L.

In the second study 10 male and 5 female CD Sprague-Dawley rats were exposed for 4 hours to 5.5 mg/L test substance aerosol by nose/head only inhalation (Hoffman, 1999). No mortalities occurred during the study period. Nasal discharge was noted as the only sign of clinical toxicity. The test group females lost weight during the first week after the test material exposure, but gained weight during the second week after exposure. In all other animals no effect on body weight was noted. Necropsy examination revealed no substance-related findings. The LC50 was therefore found to be greater than 5.50 mg/L.

 

In summary, the LC50 of Fatty acids, C5-9 tetraesters with pentaerythritol is greater than 5.5 mg/L.

CAS 68424-31-7

An acute inhalation toxicity study was performed with Fatty acids, C5-10, esters with pentraerythritol (CAS 68424-31-7) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Some clinical signs were noticed, which consisted of hunched position, chromodacryorrhea, piloerection, staining around nose and wet fur. These signs however occurred during or just after exposure and were clearly consistent with the use of restraint for exposure. The LC50 was therefore found to be greater than 5.1 mg/L.

CAS 85536-35-2

An acute inhalation toxicity study was performed with Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2) comparable to OECD Guideline 403. 5 male and female Alpk:APfSD rats were exposed for 4 hours to 5.0 mg/L test substance aerosol by nose only inhalation (Parr-Dobrzanski, 1994). The test substance caused no mortality, body weight changes or abnormalities in necropsy during the 15 day study period. Clinical signs during and immediately after exposure included hunched posture, chromodacryorrhea, piloerection, stains around the nose and wet fur. In general, animals showed a rapid recovery from these effects by Day 2, although, hunched posture and piloerection persisted in few animals to Days 4 and 8, respectively. No effect on body weight was noted. Necropsy and histopathological examination revealed non substance-findings. The LC50 was therefore found to be greater than 5.0 mg/L.

Acute Dermal Toxicity

For acute dermal toxicity, one study is available for the NPG esters and was considered for assessment of 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4). No reliable studies on the acute dermal toxicity are available for NPG esters within the polyol esters category. In regard to the estimated low dermal absorption calculated with DERMWIN (v 2.0, 2011, see toxicokinetic chapter), dermal uptake of the sub-category members is considered as low. Therefore, dermal exposure for the NPG esters within the polyol esters category is not expected to be associated with any adverse effects on human health as dermal absorption can be considered as nearly negligible.

CAS 42222-50-4

An acute dermal toxicity study was performed with 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4) according to OECD Guideline 402 (standard acute method, limit test) and GLP (Haferkorn, 2012). Five WiCD/Crl:CD(SD) rats per sex were dosed 2000 mg/kg bodyweight for 24 hours on the back skin under occlusive conditions. The animals were subjected to daily observations and body weights were determined prior to test material administration and weekly thereafter. Skin reactions (erythema and oedema) were observed and scored 24, 48, 72 and 96 h after test substance application (Days 2-5), as well as on Days 8-12 during the 14-day observation period. Macroscopic examinations were performed after terminal sacrifice. No mortality occurred and no clinical signs of systemic toxicity were observed during the study period. No skin erythema and edema (scores 0) were observed 24, 48 and 72 h after substance application and up to the end of the 14-day observation period. No effects on body weights were noted and necropsy revealed no treatment-related findings. The dermal LD50 value in rats was determined >2000 mg/kg bw.

For acute dermal toxicity, four studies are available from TMP esters group and were considered for assessment of TMP esters within the polyol esters category and read-across was conducted based on a category approach.

CAS 78-16-0

Two acute dermal toxicity studies are available for 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (CAS 78-16-0). Both were conducted comparable to “16 CFR 1500.40” guideline as a limit test.

In the first study, 10 New Zealand White rabbits (5 with intact, 5 with abraded skin) were exposed to 5000 mg test substance/kg bw for 24 hours on the back skin under occlusive conditions (Moreno, 1978). The observation period was 14 days. No mortality occurred during the study period.

Slight to moderate diarrhea was observed in 5/10 animals on Days 8 to 14. Slight yellow discharge around the nose of one animal was observed on Days 6, 9 and 10 and worsened on Days 11 through 14.

On Day 1, all 5 animals with intact skin and 4/5 animals with abraded skin showed moderate erythema according to the Draize scoring system. One animal with abraded skin showed slight erythema formation. No edema was observed in any animal (shaved or abraded) after 24 h. No necropsy was performed. Thus, the acute dermal LD50 in rabbits was found to exceed 5000 mg/kg bw.

In the second study, 10 albino rabbits (5 with intact and 5 with abraded skin) were exposed to 2000 mg/kg bw test substance for 24 hours (Morgareidge, 1974). No mortalities or clinical signs were observed. Therefore, the LD50 was found to exceed 2000 mg/kg bw. In summary, the LD50 was found to exceed 2000 mg/kg bw.

CAS 11138-60-6

An acute dermal toxicity (limit test) was performed on Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS 11138-60-6) according to OECD Guideline 402 and GLP (Blanset, 1997). 5 male and female New Zealand White rabbits were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No mortality or clinical signs of systemic toxicity were noted in any animal during the study period. 4 male animals lost 0.1 kg body weight whereas the remaining animals had a constant body weight over the study period. Necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rabbits for Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol was found to exceed 2000 mg/kg bw.

CAS 403507-18-6

An acute dermal toxicity (limit test) was performed on Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) according to OECD Guideline 402 and GLP (Sanders, 2004). 5 male and female Sprague-Dawley CD (Crl: CD IGS® BR) rats each were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No mortality, clinical signs of systemic toxicity and changes in body weight were noted in any animal during the study period. Necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane was found to exceed 2000 mg/kg bw.

For acute dermal toxicity, two studies are available for the PE esters and were considered for assessment of members of PE esters within the polyol esters category and read-across was conducted based on a category and/or approach.

CAS 71010-76-9

An acute dermal toxicity study (limit test) was performed on Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid (CAS 71010-76-9) comparable to OECD Guideline 402 and GLP (Mallory, 2006). 5 male and female Sprague-Dawley rats were exposed to 2000 mg test substance /kg bodyweight for 24 hours on the back skin under semiocclusive conditions. The observation period was 14 days. No clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats for Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid was found to exceed 2000 mg/kg bw.

CAS 62125-22-8

An acute dermal toxicity test (limit test) was performed on 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) according to OECD Guideline 402 and GLP (Debets, 1984). 5 male and female Wistar rats each were exposed to 2000 mg test substance /kg bw for 24 hours on the back skin under occlusive conditions. The observation period was 14 days. No mortality and clinical signs of systemic toxicity were noted in any animal during the study period. Body weight gain and necropsy at study termination revealed no abnormalities. Thus, the acute dermal LD50 in rats 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) was found to exceed 2000 mg/kg bw.

Conclusion for acute toxicity

Several studies are available investigating the acute oral toxicity of polyol esters category members resulting in oral LD50 values greater than 2000 mg/kg bw. Five reliable studies investigating the acute inhalation toxicity within the polyol esters category are available resulting in LC50 values > 5.0 mg/L. Seven reliable acute dermal toxicity studies consistently showed no effects at the limit dose of 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, inhalation and dermal toxicity was identified. 

 

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 category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category 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.