Registration Dossier

Administrative data

Description of key information

Repeated dose toxicity: Oral NOAEL (rat, m/f): 1000 mg/kg bw/day (OECD 408, category approach)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity

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).

 

Data matrix

CAS #

NOAEL (rat)

[mg/kg bw/day]

627-83-8 (a)

RA: CAS 68583-51-7

RA: CAS 1323-39-3

RA: CAS 151661-88-0

68583-51-7

1000 (m,f)

84988-75-0

RA: CAS 68583-51-7

RA: CAS 1323-39-3

RA: CAS 151661-88-0

624-03-3

RA: CAS 68583-51-7

RA: CAS 1323-39-3

RA: CAS 151661-88-0

91031-31-1

RA: CAS 68583-51-7

RA: CAS 1323-39-3

RA: CAS 151661-88-0

1323-39-3 (b)

7355 (f)

5657 (m)

151661-88-0

1000 (m,f)

 4219 -49 -2   

RA: CAS 68583-51-7

RA: CAS 1323-39-3

RA: CAS 151661-88-0

(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.

 

CAS 68583-51-7

Decanoic acid, mixed diesters with octanoic acid and propylene glycol was tested for subchronic oral toxicity in a 90-day study according to OECD guideline 408 in compliance with GLP (Pittermann, 1993).

Groups of 10 Wistar rats per sex and dose were given 100, 300 and 1000 mg/kg bw/day of the test material in peanut oil by gavage, 5 days/week for 13 weeks. A concurrent negative control group receiving the vehicle only was included. Furthermore, additional satellite control and high-dose groups with 5 animals per sex were included in the study for investigating the reversibility of possible effects after a 34-day post-exposure recovery period. No clinical signs or mortality occurred in relation to the test substance during the study period in any animal. During the study period, 5 animals out of different groups died at blood collection time points (no further information). No adverse effects on body weight or body weight gain were noted. Higher food consumption in the additional male high-dose group was observed due to higher body weight at start of the study. An increase in food consumption in the female high-dose group in Week 10, 12 and 13 was observed due to one animal caged individually. The water consumption of the male and female test groups showed no dose-related variations or reductions. Ophthalmoscopic examinations revealed no treatment related findings. No treatment-related changes in the haematological and clinical parameters and organs weights were measured. During gross pathology and histopathology no treatment-related findings were observed. Furthermore, the animals of the recovery groups showed no macroscopical compound-related alterations in the observed organs.

Based on the lack of adverse effects, a NOAEL of 1000 mg/kg bw/day (m, f) was identified in this study.

CAS 1323-39-3

Stearic acid, monoester with propane-1,2-diol was tested in subchronic studies via the oral route following a protocol similar to OECD guideline 408 (Saatman, 1967). Stearic acid, monoester with propane-1,2-diol was administered to groups of 24 Sprague-Dawley rats per sex and dose at 1.5, 3.36 and 7.52% in the diet (calculated doses: 1158, 2571 and 5657 mg/kg bw/day (males) and 1461, 3214 and 7355 mg/kg bw/day (females)) for a period of 90 days. Furthermore, a group receiving an isocaloric control diet containing 7.52% mono-and diglycerides was included as control group. In all treatment groups, the total fat additive in the diet was equal to 7.52% by substitution with a control fat mono-and diglycerides.

No mortality occurred during the study period in any animal. A mild respiratory infection of the pleuro-pneumonia-like organism type was present in the weanling rats when they were assigned to the diets but the majority of the animals showed no observable signs of infection after the first few weeks on test. No significant difference in growth rate was observed in females. The mean body weight of male rats fed 1.5% of the test substance in the diet was significantly higher during Week 6 and 7. No effects on food efficiency were observed. A non-adverse increase in water consumption was seen in different groups during the study period without a dose-relationship. Blood chemical analyses, haematological determinations and urine analysis showed no finding in incidence or concentration considered to be substance-related. When organ to body weight or brain weight ratios for each experimental group of rats were compared separately with the control group, no biologically relevant differences were observed. During gross pathology, a very high incidence of demonstrable lung involvement was observed upon necropsy of the rats in this study. 163/192 rats showed gross lung pathology. These findings, mainly diffuse congestion and consolidation, were not related to any diet or sex but reflected a general condition of the entire group of rats. Histopathology revealed no substance-related adverse effects.

Based on the lack of adverse effects, a NOAEL of 7.52 % in the diet equivalent to the calculated doses of 7355 mg/kg bw/day (f) and 5657 mg/kg bw/day (m) was identified in this study.

 

CAS 151661-88-0

Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol were tested in subchronic studies via the oral route following a protocol similar to OECD guideline 408 (Pittermann, 1991). Groups of 10 Wistar rats per sex and dose were given 100, 300 and 1000 mg/kg bw/day of the test material in peanut oil by gavage, 5 days/week for ca. 13.5 weeks. A concurrent negative control group receiving the vehicle only was included. Furthermore, additional satellite control and high-dose groups with 5 animals per sex and dose were included in the study for a 32-33-day recovery period. No mortality or clinical signs of toxicity occurred during the study period. The total body weight gain of all groups showed no deviation and was comparable to the control group. The mean food and water consumption in all treated groups was comparable to the control group. Relative and absolute organ weights showed no substance-related differences to the control group.

Haematological parameters showed few and slight differences to the control values and were considered incidental The biochemical examinations revealed dose-independent findings which were not considered to be substance-related. The opthalmoscopic examinations showed no compound-related effects. The absolute and relative organ weights in all groups showed no deviations and were comparable to the control. The macroscopical examination of the organs displayed some spontaneous observations like discolouration of the thymus but no compound-related macroscopical effects were observed. However, in the male and female animals of all groups (including the recovery and control groups) the livers, the heart and the mandibulary lymph node showed effects which were due to a bacteriosis of unknown etiology. The liver and the heart of the recovery groups (high-dose group and control group) showed the same signs of bacteriosis and therefore prove the persistence of the bacteriosis. The histopathologic examination revealed no compound-related effects.

Based on the lack of adverse effects, a NOAEL of 1000 mg/kg bw/day (m, f) was identified in this study.

Conclusion for subchronic repeated dose toxicity, oral

In summary, subchronic oral administration of three substances of the Glycol Ester category: Stearic acid, monoester with propane-1,2-diol, Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol and Decanoic acid, mixed diesters with octanoic acid and propylene glycol, consistently showed no adverse systemic effects resulting in NOAELs of 1000 mg/kg bw/day.

There are no data available on the repeated dose toxicity after dermal application and inhalation of the category members.

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 repeated dose 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.