Decanoic acid, mixed diesters with octanoic acid and triethylene glycol

Endpoint summary

Description of key information

In an acute oral toxicity study in male and female Wistar rats with the test substance, no deaths or adverse clinical signs were noted. There were no adverse necropsy findings. The acute oral LD 50 value was found to be greater than 5000 mg/kg bw.

In an acute dermal toxicity study in male and female New Zealand White rabbits with a surrogate material, no deaths were noted during the observation period. There were no necrospsy findings. The acute dermal LD 50 value was found to be greater than 20 g/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 19, 1995 to October 13, 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Version / remarks:

July 1, 1991

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

The test substance was received from the C.P. Hall Company on July 5, 1995. The BIN number was 024910

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Wistar-strain, albino rats were used for this test. Animals were obtained from Ace Animals, Inc., in Boyertown, PA., in equal numbers of each sex, between 200 and 300 grams bodyweight, and approximately six to nine (6 to 9) weeks of age.

Upon receipt, animals were carefully checked for respiratory difficulty, ocular or nasal lacrimation, dehydration, diarrhea, and general condition.

Animals were acclimated for eight (8) days prior to test initiation. They were housed in stainless steel cages with indirect bedding, in a room with a 12 hour light/dark cycle. The room temperature was controlled, to provide for the health and comfort of the animals with an approximate range of 65° to 75° F. The humidity was also monitored. Diet consisted of Lab Diet Certified Rodent Diet #5002, as well as water, ad libitum.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Rats received a single bolus dose by oral gavage at a calculated dose of 5,000 mg/kg bw.

Doses:

A single 5,000 mg/kg bw dose was administered.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Prior to test initiation, the test article's mass to volume relationship (specific gravity) was determined to facilitate volumetric dosing.

Twenty-four (24) hours prior to test initiation, the rats were reexamined for general condition as described above. A group of five (5) male and five (5) female rats, of sufficient weight to assure a fasted bodyweight between 200 and 300 grams, was labelled and set aside.

The following day, after approximately 18 hours of fasting, each rat was weighed and marked with an ear clip. The weight variation of animals used did not exceed +20% of the mean weight for each sex. Individual doses, calculated on the basis of bodyweight, were administered using a stainless steel intragastric feeding needle, of sufficient bore to allow even passage of the test article. Rats were then returned to their cages, where food and water were available ad libitum. Each cage was labelled uniquely with respect to job number, test article, dose level, sex, animal number(s), and date of dosing.

Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6, and 24 hours post-dosage. Observations were made at least once daily thereafter for a total of 14 days. Interim bodyweights were recorded on day seven (7).

Animals sacrificed at the end of the 14 day observation period were subjected to complete gross necropsy, with all findings noted. Sacrificing was accomplished via carbon dioxide asphyxiation.

Statistics:

Not stated

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None recorded

Clinical signs:

other: No adverse clinical signs were reported. All rats reported as normal at all observation points.

Gross pathology:

No gross changes observed.

Acute Oral Toxicity in Rats - Bodyweights

Dose Level: 5,000 mg/kg bw

Animal Number and Sex	Bodyweight (grams)	Day 7	Termanal	Change (+/-)
1 M	230	309	344	+114
2 M	218	305	338	+120
3 M	237	307	340	+103
4 M	228	300	332	+104
5 M	233	342	384	+151
6 F	220	262	282	+62
7 F	218	251	264	+46
8 F	224	262	284	+60
9 F	246	264	270	+24
10 F	236	243	260	+24

 

Conclusions:

The acute oral LD50 in male and female rats is > 5,000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key result is based on a guideline study conducted in rats. Supporting data from stucturally similar ester materials further supports the low acute oral toxicity of the test substance.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Read across to members of the US HPV Glycol Esters category. See attached file.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

other: A limit dose was administered

Remarks on result:

not determinable due to absence of adverse toxic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

20 000 mg/kg bw

Quality of whole database:

The key result is based on a guideline study conducted in rabbits.

Additional information

The test substance is a member of a category of aliphatic esters submitted by The American Chemistry Council's (ACC) Aliphatic Esters Panel (Panel) under the High Production Volume (HPV) Chemical Challenge Program (ACC, 2003). Information from a Screening Information Data Set (SIDS) developed in that program serves as supplementary or weight-of-evidence information in the current dossier. The glycol esters chosen to supply additional information are very closely related in molecular structure They exhibit similar behavior with respect to physicochemical , environmental fate. Category ester compounds with similar structures and functionalities were of low acute oral toxicity in rats. In the first of three studies conducted in rats, heptanoic acid, oxybis(2,1 -ethanediyloxy-2,1 -ethanediyl)ester (CAS 70729 -68 -9) displayed little or no toxicity in male or female Wistar rats up to a limit gavage dose of 2000 mg/kg bw. No mortality was reported in this study. Limited clinical signs included slight piloerection and sporadic findings. Similarly, CAS 70729 -68 -9 displayed little or no acute toxicity when administered by gavage to male rats at a limit dose of 25 g/kg bw. There was only one mortality. Clinical signs included hyperemia, lethargy and prostration. In a third study with CAS 70729 -68 -9, the acute oral LD50 of the test substance in females rats after gavage administration was > 24 g/kg bw and < 25 g/kg bw. All deaths occurred within 2 days of dosing. At this elevated dose level, clinical observations included flat body posture, moribundness, labored breathing, stained/wet perineal area, lacrimation, stained face, weakness, ataxia, lethargy, prostration, salivation and chromodacryorrhea. Information from a secondary source reports LD50 values in rats of 12.5 g/kg bw and 31.4 g/kg bw for the test material 2,2'-ethylenedioxydiethyl bis(2 -ethylhexanoate) (CAS 94 -28 -0). Heptanoic acid, ester with 2,2,4 -trimethyl-1,3 -pentanediol (CAS 71839 -38 -8) displayed an acute oral LD50 of > 2000 mg/kg in male and female rats. 2 -Ethylhexanoic acid, diester with tetraethyleneglycol (CAS 18268 -70 -7), when tested in male and female Sprague-Dawley rats, caused no deaths and only minimal clinical changes that resolved by 3 to 5 days of observation. The acute oral LD50 was found to be >5000 mg/kg bw.

Justification for classification or non-classification

Based on the results of acute oral and dermal toxicity testing in rats with the test substance or a surrogate, the test substance would not be classified for acute toxicity according to the European Regulation (EC) No. 1272/2008 on classification and labelling of chemicals.