Bis(2-ethylhexyl) carbonate

Endpoint summary

Description of key information

Acute toxicity data for Bis(2-ethylhexyl) carbonate are available for the oral and the dermal route. Acute animal studies by inhalation route are scientifically unjustified as inhalation is not a relevant route of exposure to Bis(2-ethylhexyl) carbonate. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used. 
In rats, the substance is practically non-toxic with oral and dermal LD50 values of > 2 000 mg/kg bw. Neither the oral nor the dermal application of 2000 mg/kg bw induced  deaths, clinical signs, changes in body weight or treatment related necropsy findings.

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:

2002-01-23 to 2002-02-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 March 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

amended Directive (96/54/EEC) dated 30 September 1996, Annex IVB

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: males: 246 - 270 g; females: 163 - 167 g
- Fasting period before study: Fasted from 16 h before until 3-4 h after the administration of the test article. Water was available ad libitum during this period.
- Housing: housed collectively at 3 animals per cage (Makrolon® III)
- Diet: ad libitum, standard laboratory rat diet Teklad Global 18 % Protein Rodent Diet (pelleted diet, batch no.: H141) produced by Harlan Teklad, Shaw's farm, Blackthorn Bicester, Oxon, OX6 OTP, England
- Water: ad libitum, tap water as for human consumption
- Acclimation period: 7 days (females); 9 days (males)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: applied undiluted

MAXIMUM DOSE VOLUME APPLIED: Since the density of the liquid test article was determined as 0.89 g/ml, the test article was administered at a volume of 2.25 ml/kg body weight which corresponded to a dose of 2000 mg/kg bw.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The test was carried out in one step in 3 female and 3 male animals. Initially, the dose of 2000 mg/kg bw was administered to 3 female rats. Since no mortality was observed within 48 hours, the test article was administered subsequently to 3 male rats at the same dose of 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations : In each animal a number of clinical-toxicological signs were evaluated according to a modified IRWIN Screening procedure and observed findings were recorded. The animals were examined during 10 min after dosing and at the following post-treatment intervals: 1 h, 2 h, 6 h, 24 h and thereafter once daily up to day 14.
- Frequency of weighing: Body weights were recorded immediately before treatment and on days 7 and 14 p.a. (termination).
- Necropsy of survivors performed: yes

Statistics:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: approx. 100 % a.i.; no animal died

Mortality:

0/6 - No animal died during the course of the 14-day observation period following the orally administered dose of 2000 mg/kg bw.

Clinical signs:

other: No clinical signs were observed during the 14-day observation period.

Gross pathology:

Gross pathological examinations on day 14 p.a. (terminal necropsy) did not reveal abnormal macroscopic findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

On the basis of the results obtained after a single oral administration in rats, the oral LD50 of Bis(2-ethylhexyl) carbonate was determined to be > 2000 mg/kg bw. No significant clinical signs, changes in body weight or gross pathological findings were observed.

Executive summary:

In an acute oral toxicity study according to EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method) dated 30 September 1996 and OECD Guideline 423, 22 March 1997, 3 male and 3 female young adult Wistar rats were given a single oral dose of Bis(2-ethylhexyl) carbonate, approx. 100 % a.i.) at a dose of  2000 mg/kg bw (limit test) and observed for 14 days.

 

Oral LD₅₀ Males and Females > 2000  mg/kg bw

No animal died during the course of the 14-day observation period following the dose of 2000 mg/kg bw.

No clinical signs were observed.

There was no influence of the treatment on the body weight development in all male and female animals during the 14-day observation period.

Gross pathological examinations on day 14 p.a. did not reveal any finding.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

2004-12-06 to 2004-12-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 Feb, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Directive 92/69

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

EPA 712-C-98-192, August, 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: male 233 - 245 g, female 203 - 237 g
- Fasting period before study: none
- Housing: Macrolon cages on Altromin saw fiber bedding
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Water: ad libitum, tap water (drinking water, municipal residue control, microbioI. controlled periodically)
- Acclimation period: Adequate acclimatization period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): l0
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of the total body surface, approximately 24 hours before the test, fur was removed from the dorsal area of the trunk by clipping.
- Type of wrap if used: The test item was applied to the patch first, and then applied to the skin. Test item was held in contact with the skin with a gauze-dressing and nonirritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing mentioned
- Time after start of exposure: patch removal after 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): applied undiluted

VEHICLE
- no vehicle used

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- The animals were weighed prior to application and once a week thereafter.
-- A careful clinical examination was made at least twice a day on the day of dosing and once a day thereafter. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes

Statistics:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: approx. 100 % a.i; no animal died

Mortality:

0/10

Clinical signs:

other: No clinical signs of toxicity were observed throughout the observation period. The skin at the application site showed no changes.

Gross pathology:

Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

On the basis of the results obtained after a single dermal administration in rats, the dermal LD50 of Bis(2-ethylhexyl) carbonate was determined to be > 2000 mg/kg bw. No significant clinical signs, changes in body weight or gross patological findings were observed.

Executive summary:

In an acute dermal toxicity study performed as limit test according to the guidelines OECD 402, adopted 24 Feb. 1987, Directive 92/69 EU Method B.3 (Acute Toxicity (Dermal)) and OPPTS 870.1200, EPA 712-C-98-192, August 1998, 5 female and 5 male young adult Wistar rats were dermally exposed to Bis(2-ethylhexyl) carbonate (99 - 100 % a.i.) for 24 hours to 10% of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD₅₀ Males and Females >  2000 mg/kg bw

No mortality occured in this limit test.

No clinical signs of toxicity were observed throughout the observation period.

The skin at the application site showed no changes.

Weight gain of all animals was within the expected range.

No test substance related gross pathological changes were found in any animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

In an acute oral toxicity study according to EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method) dated 30 September 1996 and OECD Guideline 423, 22 March 1997, 3 male and 3 female young adult Wistar rats were given a single oral dose of Bis(2-ethylhexyl) carbonate, approx. 100 % a.i.) at a dose of  2000 mg/kg bw (limit test) and observed for 14 days. 

Oral LD₅₀ Males and Females > 2000  mg/kg bw

No animal died during the course of the 14-day observation period following the dose of 2000 mg/kg bw.

No clinical signs of toxicity were observed.

There was no influence of the treatment on the body weight development in all male and female animals during the 14-day observation period.

Gross pathological examinations on day 14 p.a. did not reveal any finding.

In an acute dermal toxicity study performed as limit test according to the guidelines OECD 402, adopted 24 Feb. 1987, Directive 92/69 EU Method B.3 (Acute Toxicity (Dermal)) and OPPTS 870.1200, EPA 712-C-98-192, August 1998, 5 female and 5 male young adult Wistar rats were dermally exposed to Bis(2-ethylhexyl) carbonate (99 - 100 % a.i.) for 24 hours to 10 % of body surface area at a dose of  2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD₅₀ Males and Females >  2000 mg/kg bw

No mortality occured in this limit test.

No clinical signs of toxicity were observed throughout the observation period.

The skin at the application site showed no changes.

Weight gain of all animals was within the expected range.

No test substance related gross pathological changes were found in any animals.

Based on the available information, Bis(2-ethylhexyl) carbonate is non-toxic by oral and dermal administration in rat. There are no data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there is no reason to believe that there is acute toxicity relevant to humans for this route of exposure. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for selection of acute toxicity – oral endpoint
study according to OECD and EU guidelines, no deviations, GLP

Justification for selection of acute toxicity – dermal endpoint
study according to OECD and EU guidelines, no deviations, GLP

Justification for classification or non-classification

Bis(2-ethylhexyl) carbonate does not comply with the classification requirements regarding acute toxicity outlined in regulation (EC) No 1272/2008 or the former European directive on classification and labeling Directive 67/548 EEC. There is no evidence on relevant intrinsic acute toxic activity of Bis(2-ethylhexy) carbonate. In rats, oral as well as dermal LD₅₀ values are greater than 2000 mg/kg bw based on a.i.. Data on inhalative acute toxicity are not availabe. However, acute animal studies by inhalation route are scientifically unjustified as inhalation is not a relevant route of exposure to Bis(2-ethylhexyl) carbonate.