Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers

Endpoint summary

Description of key information

Oral (WoE): LD50 > 2000 mg/kg bw 
 Inhalation (OECD 436): LC50 > 5.22 mg/L
 Dermal (OECD 402): LD50 > 2000 mg/kg bw 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance iwth Annex XI, 1.2 of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similar functional groups and similar precursors/breakdown products (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similar functional groups and similar precursors/breakdown products (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

There are no data available for the acute oral, inhalation and dermal toxicity of Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for the read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a comparable pattern as a result of structural similarity, the substances 9-Octadecenoic acid (Z)-, ester with 2,2-dimethyl-1,3-propanediol (CAS 67989-24-6), 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4), Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5), and Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) are selected as source substances.

Acute toxicity: oral

CAS 67989-24-6

An acute oral toxicity study was performed with 9-octadecenoic acid (Z)-, ester with 2,2-dimethyl-1,3-propanediol (CAS 67989-24-6) according to a protocol 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. 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 set at > 2000 mg/kg bw.

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, 1997). 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 set at > 2100 mg/kg bw.

CAS 147256-33-5

A GLP-conform acute oral toxicity study with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane was performed in female Wistar (RccHanTM:WIST) rats according to the acute toxic class method described in OECD guideline 423 (Sanders, 2012). In two sequential steps, the undiluted test substance was administered to 3 animals per step at a dose level of 2000 mg/kg bw via oral gavage. In both treatment steps, no mortalities and no clinical signs of toxicity were observed up to the end of the 14-day study period. All animals showed the expected gains in body weight and no abnormalities were observed at necropsy. Based on these results, the experimental oral LD50 in rats was greater than 2000 mg/kg bw. According to OECD guideline 423, an oral LD50 cut-off greater than 5000 mg/kg bw was derived.

Acute toxicity: inhalation

CAS 68855-18-5

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) and under GLP conditions. Three RccHanTM:WIST rats/sex were exposed for 4 h 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. No mortality occurred throughout the study period. Signs of hunched posture and piloerection were commonly seen in animals for a short period after removal from the exposure chamber following exposure. 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, hunched posture as well as occasional instances of piloerection. 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 that did not gain 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 detailed macroscopic examination of the respiratory tract did not reveal signs of irritancy or local toxicity. The inhalation LC50 value in rats was determined to be > 5.22 mg/L.

Acute toxicity: dermal

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 under GLP conditions (Haferkorn, 2012). Five WiCD/Crl:CD(SD) rats per sex were exposed to 2000 mg/kg bw for 24 hours on the back skin under occlusive conditions. Skin reactions (erythema and oedema) were 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 to be > 2000 mg/kg bw.

In addition, based on a QSAR calculated dermal absorption value range of 8.15*10E-9 - 6.92*10E-14 mg/cm²/h a low potential for dermal absorption is predicted for Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers (Dermwin v.2.02, 2012). Thus, dermal absorption of Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers can be considered as nearly negligible.

Conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers is not considered to be hazardous following acute exposure.

 

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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 analogue concept is applied to Reaction products from the esterification of neopentylglycol with fatty acids, C16-18 (even numbered) and C18-unsatd. and fatty acids, C18-unsaturated, dimers, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.