Reaction mass of bis(2-ethylhexyl) adipate and cyclohexyl 2-ethylhexyl adipate and dicyclohexyl adipate

Endpoint summary

Description of key information

LD50 (oral, rat): > 2000 mg/kg bw

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:

07/05/2018 - 18/07/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Analysis of the test item was carried out at BASF SE, Germany.
Information on stability or characterization of the test item, which appropriately defines the test batch, is under the responsibility of the sponsor.
Name of test item:
Reaction mass of Hexanedioic acid, 1-cyclohexyl 6-(2-ethylhexyl) ester, Hexanedioic acid, 1,6-dicyclohexyl ester and Hexanedioic acid, 1,6-bis(2-ethylhexyl) ester
Test item No.: 18/0104-1
Batch identification: #30869
CAS No.: CAS No. 849-99-0; CAS No. 77357-98-3; CAS No. 103-23-1
Purity: 99.8 area-% (GC, DB-1 capillary) 99.7 area-% (GC, DB-1701 capillary). For details see analytical report 18L00098.
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: January 31, 2019
Storage conditions: Room temperature
Physical state / color: Liquid / colorless, clear
Density [g/mL]: 0.972 (determined by Bioassay Laboratories)

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age on day 0: Young adult animals (female animals approx. 10 weeks)
Supplier: Charles River Wiga GmbH, Germany
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight (± 20% of the mean weight)

HOUSING AND DIET
Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C +- 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Air changes per hour: Approx. 10
Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing
Feeding: R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany), ad libitum
Drinking water: Tap water ad libitum
Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
Enrichment: Wooden gnawing blocks (Type NGM E-022); ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test item homogenization until the end of each administration period: The homogeneity of the test item during administration was ensured by stirring with a magnetic stirrer.
Form of administration: Undiluted
Route of administration: Single oral administration by gavage.
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Observation period: 14 days
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Histology: No histological examinations were performed.

By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals.
Because no mortality occurred, a further dose of 2000 mg/kg bw was administered to another group of 3 female animals in the second step.

Statistics:

Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in both test groups.

Clinical signs:

other: Impaired general state and piloerection were observed in all animals of the first and second 2000 mg/kg bw test group from hour 2 or 3 until hour 4 after administration.

Gross pathology:

There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (6 females).

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of Reaction mass of Hexanedioic acid, 1-cyclohexyl 6-(2-ethylhexyl) ester, Hexanedioic acid, 1,6-dicyclohexyl ester and Hexanedioic acid, 1,6-bis(2-ethylhexyl) ester after oral administration was found to be greater than 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the undiluted test item Reaction mass of Hexanedioic acid, 1-cyclohexyl 6-(2-ethylhexyl) ester, Hexanedioic acid, 1,6-dicyclohexyl ester and Hexanedioic acid, 1,6-bis(2-ethylhexyl) ester was administered by gavage to two test groups of three fasted female Wistar rats each The following test substance related clinical observations were recorded, clinical signs occurred within the first 4 hours after administration: 2000 mg/kg (first and second test group): No mortality occurred, impaired general state in all animals, piloerection in all animals. All animals gained weight in a normal range throughout the study period. There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (6 females). The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the results of the acute toxicity testing, the test item was not classified and labelled according to Regulation (EC) No 1272/2008 (CLP).