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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Oral LD50 = 64000 mg/kg bw (target substance) and 12900 mg/kg bw (read-across from CAS 105-99-7), weight of evidence approach

Inhalatory LC50 > 5.7 mg/L air (read-across from CAS 103-23-1)

Dermal LD50 > 5000 mg/kg bw (read-across from CAS 16958-92-2)

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 and reliable studies (Klimisch scores 2). The selected studies are sufficient to fulfil the standard information requirements set out in Annex VII, 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 adequate and reliable studies (Klimisch scores 1-2). The selected studies are 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 adequate and reliable studies (Klimisch score 2). The selected studies are 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

Reliable data on acute oral, inhalation and dermal toxicity of bis(1-methylheptyl) adipate (CAS 108-63-4) are not available. The assessment of acute toxicity was therefore based on studies conducted with analogue source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Oral

The acute oral toxicity potential of the target substance was evaluated in a weight of evidence approach, taking into account several reliable acute oral toxicity studies performed with appropriate source substances and published information from the target substance.

CAS 108-63-4

Based on the information provided in the High Production Volume (HPV) Chemical Challenge Program: Test Plan for Aliphatic Esters Category (EPA, 2001), a LD50 value of > 64000 mg/kg bw has been reported for the target substance.

CAS 110-33-8

The acute oral toxicity of dihexyl adipate was investigated in a study similar to OECD guideline 401 (Younger Laboratories, 1972). Groups of each 5 male and female Sprague Dawley rats were administered the test substance via oral gavage at dose levels of 10000, 12600 and 15800 mg/kg bw followed by an observation period of 7 days. Mortalities occurred during Days 1 and 3 of the study in 1 female as well as in 1 male and 1 female at dose levels of 12600 and 15800 mg/kg bw, respectively. No mortalities were observed at 10000 mg/kg bw during the whole study period. Clinical signs of toxicity in survivors included reduced appetite and reduced activity 2 to 3 days after application of the test substance. Furthermore, increasing weakness and collapse were observed. At study termination, body weights of males and females were comparable within the treatment groups. Autopsy of deceased animals revealed haemorrhage of the lung, decolouration of the liver and acute gastrointestinal inflammation. In surviving animals, no abnormal findings were observed in viscera at macroscopic examination. Based on the results of this study, the oral LD50 value for male and female Sprague Dawley rats was greater than 15800 mg/kg bw.

CAS 103-23-1

In acute toxicity tests, groups of five males and five females of F344 rats were administered a single dose of bis(2-ethylhexyl) adipate in corn oil by gavage (NTP, 1982). The estimated LD50 values as given in the report were 45000 mg/kg bw for male rats and 24600 mg/kg bw for female rats.

CAS 105-99-7

In an acute oral toxicity study, dibutyl adipate diluted in water was administered via gavage to 6 male Wistar rats at different doses (Smyth et al., 1951). One week later, 6 further animals were treated with another dose of the test substance and this procedure was repeated until two dosages differing by a factor of ten were found, at which mortality was observed in some or all animals and at which some or no mortality occurred during the 14-day observation period. The oral LD50 was then estimated on the assumption that the slope of a probit mortality vs. log dosage curve is the same as that of a structurally related test material which has been studied more detailed previously. Based on the probit analysis, the oral LD50 value of Dibutyl adipate was estimated to be 12900 mg/kg bw.

CAS 16958-92-2

The acute oral toxicity of bis(tridecyl) adipate was investigated in Wistar rats according to OECD guideline 401 (MB Research Laboratories, 1978). Groups of 5 Wistar rats per sex received the test substance via gavage at a limit dose of 15000 mg/kg bw. No mortalities were observed within the 14-day observation period. Diarrhoea was noted in all animals on the day of treatment and thereafter in 1 male and 1 female on day 1, in two males from day 2 until day 4 and in 1 male on day 13 and day 14, respectively. Other clinical signs during the 14-day observation period included lethargy, flaccidity, oily bodies, ptosis and chromorhinorrhoea. Based on the results of the study, the oral LD50 value was greater than 15000 mg/kg bw for male and female Wistar rats.

Inhalation

CAS 103-23-1

The acute inhalation toxicity of bis(2-ethylhexyl) adipate (CAS 103-23-1) was investigated in a limit test conducted according to OECD guideline 403 and GLP (BASF, 1998). 5 Wistar rats per sex were exposed to the test substance as a liquid aerosol (MMAD = 1.4 µm) at an analytically determined concentration of 5.688 mg/L for 4 h using a nose/head only exposure system. No mortality occurred throughout the study period. Clinical signs of toxicity included irregular and accelerated respiration as well as attempts to escape and piloerection and were completely subsided from post dosing day 5 onward. Body weights were not affected by treatment and no abnormalities were noted at gross pathology. Based on these results, the LC50 value for male and female Wistar rats was assumed to be greater than 5.7 mg/L air.

CAS 16958-92-2

The acute inhalation toxicity of bis(tridecyl) adipate was investigated in a study similar to OECD guideline 403 (Mobil, 1989). Groups of 10 Sprague Dawley rats per sex were exposed to analytical atmosphere concentrations of the test aerosol of 0.5 and 3.2 mg/L (highest achievable dose) for 4 h using a whole body exposure system. In addition, 10 control animals per sex were sham-exposed. An interim sacrifice of 5 males and 5 females of each group was performed 1 day after exposure to the test aerosol. No mortality and no clinical signs of toxicity were observed in any of the animals during the 1- or 14-day observation period. Body and organ weights were not affected by treatment and no abnormalities were noted at gross pathology. The histopathological examination did not reveal any substance-related changes in any of the organs examined (lungs, nasal turbinates, liver, kidney and tracheobronchial lymph node). Based on these results, the LC50 value for male and female Sprague Dawley rats was assumed to be greater than 3.2 mg/L air.

Dermal

CAS 16958-92-2

The acute dermal toxicity of bis(tridecyl) adipate was investigated in New Zealand White rabbits at a limit dose of 5000 mg/kg bw according to the Federal Hazardous Substances Act Regulations (16 CFR 1500.40) (MB Research Laboratories, 1978). The test substance at a limit dose of 5000 mg/kg bw was applied to the intact and abraded skin of 5 animals, respectively, under semi-occlusive conditions for a period of 24 h. No mortalities and no effects on the mean body weights were observed up to the end of the study. Diarrhoea occurred in 2/5 animals with intact skin and 2/5 animals with abraded skin during the 14-day observation period. A bloated abdomen was observed in a single animal (intact skin) on Day 13 and 14 of the study. Further clinical signs included emaciation in 2 animals (abraded skin) as well as lethargy in one of these animals. After exposure, the test substance was removed and skin irritation was assessed according to the Draize scoring system. Erythema (grade 1 or 2) was found in 9/10 animals, whereas edema (grade 1 or 2) was only observed in 3 animals. Based on these results, the dermal LD50 value for rabbits was found to be greater than 5000 mg/kg bw.

CAS 105-99-7

In an acute dermal toxicity study, dibutyl adipate (CAS 105-99-7) was investigated in 6 rabbits at several doses differing by a factor of 10 (Smyth et al., 1951). The undiluted test substance was applied to the clipped skin of the trunk of the animals for 4 days under occlusive conditions. The dermal LD50 of Dibutyl adipate was determined graphically and assumed to be 20 mL/kg bw, which corresponded to a dose of 19220 mg/kg bw based on a density of 0.96 g/mL.

Conclusion

The reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 values and LC50 values were greater than the recommended guideline limit values. Therefore, as the available data did not identify any acute toxicity, bis(1-methylheptyl) adipate (CAS 108-63-4) is not considered to be hazardous following acute exposure via the oral, inhalation and dermal route.

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 bis(1-methylheptyl) adipate (CAS 108-63-4), data will be generated from data for 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 oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.